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In recent years, there has been an increase in the adventive establishment and spread of parasitoid wasps outside of their native range. However, lack of taxonomic tools can hinder the efficient screening of field-collected samples to document the establishment and range expansion of parasitoids on continent-wide geographic scales. Here we report that Leptopilina japonica (Hymenoptera, Figitidae), a parasitoid of the globally invasive fruit pest Drosophila suzukii (Diptera, Drosophilidae), is now widespread in much of North America despite not having been intentionally introduced. Surveys in 2022 using a variety of methods detected L. japonica in 10 of 11 surveyed USA States and one Canadian Province where it was not previously known to occur. In most surveys, L. japonica was the most common species of D. suzukii parasitoid found. The surveys also resulted in the detection of Ganaspis cf. brasiliensis (Hymenoptera, Figitidae), the recently-released biological control agent of D. suzukii, in six USA States where it had not previously been found. These new detections are likely a result of intentional biological control introductions rather than spread of adventive populations. A species-specific multiplex PCR assay was developed as a rapid, accurate and cost-effective method to distinguish L. japonica, G. cf. brasiliensis, the closely-related cosmopolitan parasitoid Leptopilina heterotoma (Hymenoptera, Figitidae) and other native parasitoid species. This dataset and the associated molecular tools will facilitate future studies of the spread and ecological impacts of these introduced parasitoids on multiple continents.

Abstract Global mean lower stratosphere temperatures rose abruptly in January 2020 reaching values not experienced since the early 1990s. Anomalously high lower stratospheric temperatures were recorded for 4 months at highly statistically significant levels. Here, we use a combination of satellite and surface-based remote sensing observations to derive a time-series of stratospheric biomass burning aerosol optical depths originating from intense SouthEastern Australian wildfires and use these aerosol optical depths in a state-of-the-art climate model. We show that the S.E. Australian wildfires are the cause of this lower stratospheric warming. We also investigate the radiatively-driven dynamical response to the observed stratospheric ozone perturbation and find a significant strengthening of the springtime Antarctic polar vortex suggesting that biomass burning aerosols play a significant role in the observed anomalous longevity of the ozone hole in 2020.

Pleural mesothelioma (PM) is a highly aggressive, fast-growing asbestos-induced cancer with limited effective treatments. There has been interest in using naturally occurring anticancer agents derived from plant materials for the treatment of PM. However, it is unclear if an aqueous extract from Leptospermum polygalifolium (QV0) has activity against PM. Here we investigated the anti-cancer properties of QV0 and Defender® (QV0 dietary formula) in vitro and in vivo, respectively. QV0 suppressed the growth of eight PM cell lines in a dose-dependent manner, effective at concentrations as low as 0.02% w/v (equivalent to 0.2 mg/ml). This response was found to be associated with inhibited cell migration, proliferation, and colony formation but without evident cell cycle alteration. We observed mitochondrial dysfunction post-QV0 treatment, as evidenced by significantly decreased basal and maximal oxygen consumption rates. Ten SCID mice were treated with 0.25 mg/g Defender® daily and exhibited reduced tumor size over 30 days, which was associated with an average extension of seven days of mouse life. There was no evidence of liver toxicity or increased blood glucose post-treatment in animals treated with Defender®. Significantly enhanced tumor apoptosis was observed in the Defender®-treated animals, correlating to mitochondrial dysfunction. Lastly, the high levels of polyphenols and antioxidant properties of QV0 and Defender® were detected in HPLC analysis. To the best of our knowledge, this study constitutes the first demonstration of an improved host survival (without adverse effects) response in a QV0-treated PM mouse model, associated with evident inhibition of PM cell growth and mitochondrial dysfunction-related enhancement of tumor apoptosis.

Background: Given the growing reliance on digital devices, an increasing number of studies have examined the effects of text medium on reading outcomes in development; however, the results have been mixed. The goal of this systematic review is to look at how print and digital formats affect reading comprehension, engagement and other reading outcomes (e.g. vocabulary, reading speed) in children and adolescents aged 1-17 years old while also considering the influence of several participant, task and study characteristics. Methods: A comprehensive search strategy involving seven electronic databases yielded 88 eligible articles comparing digital and print formats on reading outcomes published between 2000 and 2023 (3 reviewer inter-rater reliability: k = 0.54-0.78). Three major characteristics were coded: participant-level (grade/age, diverse populations, testing language); task-level (text-genre, shared reading, digital comparability); study-level (publication recency, study quality) characteristics. Contingency tables were created for all studies, then for each reading outcome and for participant, task, and study characteristics separately to classify the percentage of studies that demonstrated outcomes favouring print, digital, no difference or reliance on specific reading measures or other factors. Results: Except in the case of engagement as an outcome, the most common finding was no difference between digital and print. When participant, task and study characteristics were examined separately for the various reading outcomes, the results varied. More studies examining reading comprehension (particularly of informational text and in older children) found 'print is better', whereas 'digital is better' was more common in studies examining engagement, other outcomes such as vocabulary and diverse learners. Conclusions: This review highlights the importance of examining multiple interacting factors when studying the impact of print versus digital mediums on reading outcomes in children and adolescents.

Wildfires produce aerosols known to impact the climate, but the wider-reaching effects of this biomass burning are poorly constrained in models. Here the authors use a suite of observations from 12 campaigns around the globe to determine that the values used by most climate models overestimate the contribution of biomass burning aerosols.

Abstract We document the development of the first version of the U.K. Earth System Model UKESM1. The model represents a major advance on its predecessor HadGEM2‐ES, with enhancements to all component models and new feedback mechanisms. These include a new core physical model with a well‐resolved stratosphere; terrestrial biogeochemistry with coupled carbon and nitrogen cycles and enhanced land management; tropospheric‐stratospheric chemistry allowing the holistic simulation of radiative forcing from ozone, methane, and nitrous oxide; two‐moment, five‐species, modal aerosol; and ocean biogeochemistry with two‐way coupling to the carbon cycle and atmospheric aerosols. The complexity of coupling between the ocean, land, and atmosphere physical climate and biogeochemical cycles in UKESM1 is unprecedented for an Earth system model. We describe in detail the process by which the coupled model was developed and tuned to achieve acceptable performance in key physical and Earth system quantities and discuss the challenges involved in mitigating biases in a model with complex connections between its components. Overall, the model performs well, with a stable pre‐industrial state and good agreement with observations in the latter period of its historical simulations. However, global mean surface temperature exhibits stronger‐than‐observed cooling from 1950 to 1970, followed by rapid warming from 1980 to 2014. Metrics from idealized simulations show a high climate sensitivity relative to previous generations of models: Equilibrium climate sensitivity is 5.4 K, transient climate response ranges from 2.68 to 2.85 K, and transient climate response to cumulative emissions is 2.49 to 2.66 K TtC−1.

Since the repeal of Section 28 in 2003, research and policy reform has explored how to reduce homo/bi and transphobia to make schools more LGBTQ+ inclusive places. However, heteronormativity continues to manifest in increasingly subtle ways. This article argues that teachers must remain vigilant towards the 'Panopticon of Heteronormativity' which subtly impacts efforts to foster LGBTQ+ inclusivity. An Interpretive Phenomenological Analysis (IPA) was undertaken to capture the experience of 12 participants who advocate for LGBTQ+ inclusivity in UK primary schools. This article finds that teachers advocating for LGBTQ+ inclusivity still reinforce heteronormativity through discourses which regulate children's exposure to 'appropriate' identities, express concern about pushing an 'agenda' and LGBTQ+ teachers can experience a 'double consciousness' which complicates their efforts to disrupt heteronormativity. Recommendations include improving teacher training and practitioner awareness to critically reflect upon the subtle ways heteronormativity manifests in the classroom.

PIK3CA mutations and ARID1A loss co-exist in endometrial neoplasms. Here, the authors show that these co-mutations drive gene expression profiles correlated with differential chromatin accessibility and ARID1A binding in the endometrial epithelium, resulting in partial EMT and myometrial invasion.

BackgroundThe diagnosis of malignant pleural mesothelioma (MPM) can be difficult, in part due to the difficulty in distinguishing between MPM and reactive mesothelial hyperplasia (RMH). The tumor suppressor gene, CDKN2A, is frequently silenced by epigenetic mechanisms in many cancers; in the case of MPM it is mostly silenced via genomic deletion. Co-deletion of the CDKN2A and methylthioadenosine phosphorylase (MTAP) genes has been researched extensively and discovered to be a highly specific characteristic of MPM. Most studies have used FISH to detect the deletion of CDKN2A and IHC for MTAP as a surrogate for this. In this study, we aim to investigate and validate droplet digital PCR (ddPCR) as an emerging alternative and efficient testing method in diagnosing MPM, by particularly emphasizing on the loss of MTAP and CDKN2A.MethodsThis study included 75 formalin fixed paraffin embedded (FFPE) MPM tissue, and 12 normal pleural tissue and 10 RMH as control. Additionally, primary MPM cell lines and normal pleural samples were used as biomarker detection controls, as established in our previous publication. All FFPE specimens were processed to isolate the DNA, that was subsequently used for ddPCR detection of CDKN2A and MTAP. FFPE samples were also analyzed by fluorescence in situ hybridization (FISH) for CDKN2A and MTAP deletion, and for MTAP IHC expression. Concordance of IHC and ddPCR with FISH were studied in these samples.Results95% and 82% of cases showed co-deletion of both MTAP and CDKN2A when determined by FISH and ddPCR respectively. ddPCR has a sensitivity of 72% and specificity of 100% in detecting CDKN2A homozygous loss in MPM. ddPCR also has a concordance rate of 92% with FISH in detecting homozygous loss of CDKN2A. MTAP IHC was 68% sensitive and 100% specific for detecting CDKN2A homozygous loss in MPM when these losses were determined by ddPCR.ConclusionOur study confirms that MTAP is often co-deleted with CDKN2A in MPM. Our in-house designed ddPCR assays for MTAP and CDKN2A are useful in differentiating MPM from RMH, and is highly concordant with FISH that is currently used in diagnosing MPM. ddPCR detection of these genetic losses can potentially be utilized as an alternative method in the diagnosis of MPM and for the future development of a less-invasive MPM-specific detection technique on MPM tumor tissue DNA.

Malignant pleural mesothelioma (MPM) is an aggressive asbestos related disease that is generally considered to be difficult to diagnose, stage and treat. The diagnostic process is continuing to evolve and requires highly skilled pathology input, and generally an extensive list of biomarkers for definitive diagnosis. Diagnosis of MPM requires histological evidence of invasion by malignant mesothelial cells often confirmed by various immunohistochemical biomarkers in order to separate it from pleural metastatic carcinoma. Often when invasion of neoplastic mesothelial cells into adjacent tissue is not apparent, further immunohistochemical testing - namely BAP1 and MTAP, as well as FISH testing for loss of p16 (CDKN2A) are used to separate reactive mesothelial proliferation due to benign processes, from MPM. Various combinations of these markers, such as BAP1 and/or MTAP immunohistochemistry alongside FISH testing for loss of p16, have shown excellent sensitivity and specificity in the diagnosis of MPM. Additionally, over the recent years, research into epigenetic marker use in the diagnosis of MPM has gained momentum. Although still in their research stages, various markers in DNA methylation, long non-coding RNA, micro RNA, circular RNA, and histone modifications have all been found to support diagnosis of MPM with generally good sensitivity and specificity. Many of these studies are however, limited by small sample sizes or other study limitations and further research into the area would be beneficial. Epigenetic markers show promise for use in the future to facilitate the diagnosis of MPM.

Abstract We describe the scientific and technical implementation of two models for a core set of experiments contributing to the sixth phase of the Coupled Model Intercomparison Project (CMIP6). The models used are the physical atmosphere‐land‐ocean‐sea ice model HadGEM3‐GC3.1 and the Earth system model UKESM1 which adds a carbon‐nitrogen cycle and atmospheric chemistry to HadGEM3‐GC3.1. The model results are constrained by the external boundary conditions (forcing data) and initial conditions. We outline the scientific rationale and assumptions made in specifying these. Notable details of the implementation include an ozone redistribution scheme for prescribed ozone simulations (HadGEM3‐GC3.1) to avoid inconsistencies with the model's thermal tropopause, and land use change in dynamic vegetation simulations (UKESM1) whose influence will be subject to potential biases in the simulation of background natural vegetation. We discuss the implications of these decisions for interpretation of the simulation results. These simulations are expensive in terms of human and CPU resources and will underpin many further experiments; we describe some of the technical steps taken to ensure their scientific robustness and reproducibility.

Malignant pleural mesothelioma (MPM) is an aggressive malignancy with limited effective treatment options. Focal adhesion kinase (FAK) inhibitors have been shown to efficiently suppress MPM cell growth initially, with limited utility in the current clinical setting. In this study, we utilised a large collection of MPM cell lines and MPM tissue samples to study the role of E-cadherin (CDH1) and microRNA on the efficacy of FAK inhibitors in MPM. The immunohistochemistry (IHC) results showed that the majority of MPM FFPE samples exhibited either the absence of, or very low, E-cadherin protein expression in MPM tissue. We showed that MPM cells with high CDH1 mRNA levels exhibited resistance to the FAK inhibitor PND-1186. In summary, MPM cells that did not express CDH1 mRNA were sensitive to PND-1186, and MPM cells that retained CDH1 mRNA were resistant. A cell cycle analysis showed that PND-1186 induced cell cycle disruption by inducing the G2/M arrest of MPM cells. A protein−protein interaction study showed that EGFR is linked to the FAK pathway, and a target scan of the microRNAs revealed that microRNAs (miR-17, miR221, miR-222, miR137, and miR148) interact with EGFR 3′UTR. Transfection of MPM cells with these microRNAs sensitised the CHD1-expressing FAK-inhibitor-resistant MPM cells to the FAK inhibitor.

As one of the main drivers for climate change, it is important to understand changes in anthropogenic aerosol emissions and evaluate the climate impact. Anthropogenic aerosols have affected global climate while exerting a much larger influence on regional climate by their short lifetime and heterogeneous spatial distribution. In this study, the effective radiative forcing (ERF), which has been accepted as a useful index for quantifying the effect of climate forcing, was evaluated to understand the effects of aerosol on regional climate over a historical period (1850–2014). Eastern United States (EUS), Western European Union (WEU), and Eastern Central China (ECC), are regions that predominantly emit anthropogenic aerosols and were analyzed using Coupled Model Intercomparison Project 6 (CMIP6) simulations implemented within the framework of the Aerosol Chemistry Model Intercomparison Project (AerChemMIP) in the UK’s Earth System Model (UKESM1). In EUS and WEU, where industrialization occurred relatively earlier, the negative ERF seems to have been recovering in recent decades based on the decreasing trend of aerosol emissions. Conversely, the radiative cooling in ECC seems to be strengthened as aerosol emission continuously increases. These aerosol ERFs have been largely attributed to atmospheric rapid adjustments, driven mainly by aerosol-cloud interactions rather than direct effects of aerosol such as scattering and absorption.

With neoliberal policy central to the many challenges faced within the education system including an increasing gap between rich and poor (Reay, 2017; Giroux, 2014), this article explores how an Education Studies programme, drawing on the principles of critical pedagogy, can help students to better understand and interrogate neoliberalism and its impacts on the wider education system. Using an Interpretative Phenomenological Analysis, 19 participants participated in five focus groups. The article argues that participants demonstrate sophisticated understandings of neoliberalism's impact on themselves as students, future educators and the wider education system. They also engage in active inquiry, problematising their lives, studies and future as educators. However, students often felt a sense of hopelessness and disempowerment to change a 'fixed' system and were concerned about becoming 'part of the problem' once in practice. Consequently, we argue that whilst Education Studies programmes underpinned by critical and relational pedagogy have the potential to support student interrogation of neoliberalism, space needs to be created to foster student agency and hope for change agency once in practice. This could be achieved through students and lecturers building alliances with teachers and educators that disrupt neoliberal hegemony in practice to help students envision postneoliberal education, a deeper exploration of how neoliberalism perpetuates inequalities through classroom policies, educational materials and teacher-student relationships and greater lecturer critical reflection upon how they are complicit in the systems they wish to challenge.

For open access (OA) to become a reality, all stakeholders will need to engage positively with each other to rise to the substantial practical challenges it brings. This means moving beyond advocacy and resistance towards a more mature, evidence-based dialogue that seeks to understand all perspectives and find workable solutions. For research funders, scholarly publication delivers crucial public benefits; funders' OA mandates should be seen as tools for maximizing these benefits. The Higher Education Funding Council for England's (HEFCE) policy for open access in the next Research Excellence Framework (REF) has been put together by listening to all sides of the debate, and its success depends on continuing positive, sensitive and engaged discussions between everyone involved.

Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown etiology with platelet counts varying from 11×109/L to 186×109/L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified “pathogenic” or “likely pathogenic” variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases, including novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia.

We present a 72 × 60, angle-sensitive single photon avalanche diode (A-SPAD) array for lens-less 3D fluorescence lifetime imaging. An A-SPAD pixel consists of (1) a SPAD to provide precise photon arrival time where a time-resolved operation is utilized to avoid stimulus-induced saturation, and (2) integrated diffraction gratings on top of the SPAD to extract incident angles of the incoming light. The combination enables mapping of fluorescent sources with different lifetimes in 3D space down to micrometer scale. Futhermore, the chip presented herein integrates pixel-level counters to reduce output data-rate and to enable a precise timing control. The array is implemented in standard 180 nm complementary metal-oxide-semiconductor (CMOS) technology and characterized without any post-processing.

There is a growing elite and scholarly consensus (at least on the American left) that Justice Clarence Thomas “must immediately recuse himself from any cases relating to the 2020 election and its aftermath.” The demand is extraordinary, and as such, it has captured global attention. The dispute highlights some notable things about the Court, but it is the scandal that really captures attention. So far, calls for recusal have come almost exclusively from the left. Conservatives have dismissed the idea. What to make of it all?