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Background: Women with learning disabilities are less likely to access cervical and breast cancer screening when compared to the general population. The Social Ecological Model (SEM) was used to examine the inequalities faced by women with learning disabilities in accessing cervical and breast cancer screening in England, UK. Methods: The findings from a qualitative systematic review and a Q methodology study were triangulated. Framework analysis, in line with the SEM, was used to develop an integrated set of findings. Findings: Women with learning disabilities may lack knowledge of cancer symptoms, and cancer screening, as well as being scared about the process and getting the results. The attitudes of family and paid carers towards screening may influence women with learning disabilities' decisions as to whether screening is seen as favourable; support and training may ensure unbiased perspectives. Barriers were also associated with how cancer screening programmes are designed, such as postal invitations which assumes an ability to read. In addition, screening staff need to be aware of the general needs of people with learning disabilities, such as the benefits of easy-to-read documents. Lastly, multidisciplinary working is required so reasonable adjustments can be embedded into cancer screening pathways. Conclusion: This article highlights multiple methods to reduce the inequalities faced by women with learning disabilities, which can be achieved through reasonable adjustments. Embedding reasonable adjustments can support women with learning disabilities in making an informed decision and accessing screening if they choose to. This may result in women with learning disabilities getting a timely cancer diagnosis.

The chemokine CCL28 is highly expressed in mucosal tissues, but its role during infection is not well understood. Here, we show that CCL28 promotes neutrophil accumulation in the gut of mice infected with Salmonella and in the lung of mice infected with Acinetobacter. Neutrophils isolated from the infected mucosa expressed the CCL28 receptors CCR3 and, to a lesser extent, CCR10, on their surface. The functional consequences of CCL28 deficiency varied between the two infections: Ccl28-/- mice were highly susceptible to Salmonella gut infection but highly resistant to otherwise lethal Acinetobacter lung infection. In vitro, unstimulated neutrophils harbored pre-formed intracellular CCR3 that was rapidly mobilized to the cell surface following phagocytosis or inflammatory stimuli. Moreover, CCL28 stimulation enhanced neutrophil antimicrobial activity, production of reactive oxygen species, and formation of extracellular traps, all processes largely dependent on CCR3. Consistent with the different outcomes in the two infection models, neutrophil stimulation with CCL28 boosted the killing of Salmonella but not Acinetobacter. CCL28 thus plays a critical role in the immune response to mucosal pathogens by increasing neutrophil accumulation and activation, which can enhance pathogen clearance but also exacerbate disease depending on the mucosal site and the infectious agent.

Background Available empirical evidence on participant-level factors associated with dropout from psychotherapies for post-traumatic stress disorder (PTSD) is both limited and inconclusive. More comprehensive understanding of the various factors that contribute to study dropout from cognitive-behavioural therapy with a trauma focus (CBT-TF) is crucial for enhancing treatment outcomes.Objective Using an individual participant data meta-analysis (IPD-MA) design, we examined participant-level predictors of study dropout from CBT-TF interventions for PTSD.Methods A comprehensive systematic literature search was undertaken to identify randomised controlled trials comparing CBT-TF with waitlist control, treatment-as-usual or another therapy. Academic databases were screened from conception until 11 January 2021. Eligible interventions were required to be individual and in-person delivered. Participants were considered dropouts if they did not complete the post-treatment assessment.Findings The systematic literature search identified 81 eligible studies (n=3330). Data were pooled from 25 available CBT-TF studies comprising 823 participants. Overall, 221 (27%) of the 823 dropped out. Of 581 civilians, 133 (23%) dropped out, as did 75 (42%) of 178 military personnel/veterans. Bivariate and multivariate analyses indicated that military personnel/veterans (RR 2.37) had a significantly greater risk of dropout than civilians. Furthermore, the chance of dropping out significantly decreased with advancing age (continuous; RR 0.98).Conclusions These findings underscore the risk of premature termination from CBT-TF among younger adults and military veterans/personnel.Clinical implication Understanding predictors can inform the development of retention strategies tailored to at-risk subgroups, enhance engagement, improve adherence and yield better treatment outcomes.

Abstract In this study, we explore the utilization of penalized likelihood estimation for the analysis of sparse photon counting data obtained from distributed target lidar systems. Specifically, we adapt the Poisson Total Variation processing technique to cater to this application. By assuming a Poisson noise model for the photon count observations, our approach yields denoised estimates of backscatter photon flux and related parameters. This facilitates the processing of raw photon counting signals with exceptionally high temporal and range resolutions (demonstrated here to 50 Hz and 75 cm resolutions), including data acquired through time-correlated single photon counting, without significant sacrifice of resolution. Through examination involving both simulated and real-world 2D atmospheric data, our method consistently demonstrates superior accuracy in signal recovery compared to the conventional histogram-based approach commonly employed in distributed target lidar applications.

Tan spot (TS), known in Australia as yellow leaf spot, is caused by the fungal pathogen Pyrenophora tritici-repentis, a major foliar disease of wheat. Four experiments were conducted between 2016 and 2017 in two different climatic zones of southeastern Australia to determine the impact of TS on grain yield and quality in six wheat cultivars with different resistance ratings. In each experiment, high and low TS disease scenarios were applied to each cultivar. Disease severity was assessed as either whole-plot percentage leaf area affected (%LAA) or top three leaf (flag to flag-2) %LAA. Whole-plot %LAA was analyzed using both repeated measurements and area under the disease progress curve (AUDPC). For whole-plot %LAA, the repeated measurements identified differences in epidemic progression at key growth stages not identified through AUDPC. Both AUDPC and end-of-season flag to flag-2 %LAA were negatively correlated with grain yield and screenings. Increased rainfall impacting disease development and number of rain days above 5 mm increased TS severity across both climatic zones. Cultivar resistance ratings influenced grain yield loss, with moderately resistant, moderately susceptible, and susceptible cultivars losing up to 6, 18, and 24% grain yield, respectively. High disease significantly increased screenings by up to 1, 3, and 5% for moderately resistant, moderately susceptible, and susceptible cultivars, respectively. This study demonstrated that TS can cause significant grain yield losses in southeastern Australia, and a minimum cultivar rating of moderate resistance to moderate susceptibility was required to prevent severe TS and associated grain yield and quality losses. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

The perioperative maintenance of a patient’s core temperature is a challenge during burn care. While patient warming devices are sometimes used to prevent intraoperative hypothermia, raising the ambient temperature of the theatre is the most common practice. Theatre temperature can impact on the performance and comfort of surgery staff but standards for theatre temperatures in burn care are poorly defined. Therefore, in this study we investigated the current, global, clinical practices in burn care with respect to the ambient temperature of theatres that are used to treat severe burn injuries. An internet-based, descriptive, QualtricsXM survey was distributed electronically to 81 burn professionals to identify the temperatures at which the surgical teams operate on severe burn injuries. The survey was completed by 33 participants from 15 countries and revealed that there is a wide range of temperatures (24–45°C) at which burn injuries are treated. The prevention of hypothermia was the clinical justification most reported for those theatre temperatures. Temperatures between 26 and 30°C appear to be most comfortable for the staff. One respondent mentioned that surgeries are often limited to 5 h to avoid hypothermia in patients, however, others noted surgery durations of up to 8–12 h in raised temperatures, which may impact the physiology and performance of the team, potentially impacting the safety of the patients. The adoption of an optimal theatre temperature to address the surgical team’s comfort levels, their performance, and patient hypothermia, may improve outcomes in cases of severe burn injury.

The chemokine CCL28 is highly expressed in mucosal tissues, but its role during infection is not well understood. Here, we show that CCL28 promotes neutrophil accumulation in the gut of mice infected with Salmonella and in the lung of mice infected with Acinetobacter. Neutrophils isolated from the infected mucosa expressed the CCL28 receptors CCR3 and, to a lesser extent, CCR10, on their surface. The functional consequences of CCL28 deficiency varied between the two infections: Ccl28−/− mice were highly susceptible to Salmonella gut infection but highly resistant to otherwise lethal Acinetobacter lung infection. In vitro, unstimulated neutrophils harbored pre-formed intracellular CCR3 that was rapidly mobilized to the cell surface following phagocytosis or inflammatory stimuli. Moreover, CCL28 stimulation enhanced neutrophil antimicrobial activity, production of reactive oxygen species, and formation of extracellular traps, all processes largely dependent on CCR3. Consistent with the different outcomes in the two infection models, neutrophil stimulation with CCL28 boosted the killing of Salmonella but not Acinetobacter. CCL28 thus plays a critical role in the immune response to mucosal pathogens by increasing neutrophil accumulation and activation, which can enhance pathogen clearance but also exacerbate disease depending on the mucosal site and the infectious agent.

Abstract Dry lightning is a prevalent episodic natural ignition source for wildfires, particularly in remote regions where such fires can escalate into uncontrollable events, burning extensive areas. In this study, we aimed to understand the interplay of environmental, fuel, and geographical factors in evaluating the probability of fire initiation following dry lightning strikes in Tasmania, Australia. We integrated dry lightning, active fire records, and gridded data on fire weather, fuel, and topography into a binary classification framework for both fire‐initiating and non‐fire‐causing lightning strikes. Employing statistical and machine learning techniques, we quantified the likelihood of fire initiation due to dry lightning, with the resampled Random Forest model exhibiting notable performance with an ROC‐AUC value of 0.98. Our findings highlight how fuel characteristics and moisture content associated with particular vegetation types influence fire initiation and provide an objective approach for identifying susceptible regions of dry lightning ignitions, informing associated fire management responses.

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the gastrointestinal tract and profound alterations to the gut microbiome. Adherent-invasive Escherichia coli (AIEC) is a mucosa-associated pathobiont that colonizes the gut of patients with Crohn's disease, a form of IBD. Because AIEC exacerbates gut inflammation, strategies to reduce the AIEC bloom during colitis are highly desirable. To thrive in the inflamed gut, Enterobacteriaceae acquire the essential metal nutrient iron by producing and releasing siderophores. Here, we implemented an immunization-based strategy to target the siderophores enterobactin and its glucosylated derivative salmochelin to reduce the AIEC bloom in the inflamed gut. Using chemical (dextran sulfate sodium) and genetic (Il10-/- mice) IBD mouse models, we showed that immunization with enterobactin conjugated to the mucosal adjuvant cholera toxin subunit B potently elicited mucosal and serum antibodies against these siderophores. Siderophore-immunized mice exhibited lower AIEC gut colonization, diminished AIEC association with the gut mucosa, and reduced colitis severity. Moreover, Peyer's patches and the colonic lamina propria harbored enterobactin-specific B cells that could be identified by flow cytometry. The beneficial effect of siderophore immunization was primarily B cell-dependent because immunized muMT-/- mice, which lack mature B lymphocytes, were not protected during AIEC infection. Collectively, our study identified siderophores as a potential therapeutic target to reduce AIEC colonization and its association with the gut mucosa, which ultimately may reduce colitis exacerbation. Moreover, this work provides the foundation for developing monoclonal antibodies against siderophores, which could provide a narrow-spectrum strategy to target the AIEC bloom in Crohn's disease patients. IMPORTANCE Adherent-invasive Escherichia coli (AIEC) is abnormally prevalent in patients with ileal Crohn's disease and exacerbates intestinal inflammation, but treatment strategies that selectively target AIEC are unavailable. Iron is an essential micronutrient for most living organisms, and bacterial pathogens have evolved sophisticated strategies to capture iron from the host environment. AIEC produces siderophores, small, secreted molecules with a high affinity for iron. Here, we showed that immunization to elicit antibodies against siderophores promoted a reduction of the AIEC bloom, interfered with AIEC association with the mucosa, and mitigated colitis in experimental mouse models. We also established a flow cytometry-based approach to visualize and isolate siderophore-specific B cells, a prerequisite for engineering monoclonal antibodies against these molecules. Together, this work could lead to a more selective and antibiotic-sparing strategy to target AIEC in Crohn's disease patients.

The sea ice extent in the Weddell Sea exhibited a positive trend from the start of satellite observations in 1978 until 2016 but has shown a decreasing trend since then. This study analyzes seasonal and interannual variations in sea ice thickness using ICESat-2 laser altimetry data over the Weddell Sea from 2019 to 2022. Sea ice thickness was calculated from ICESat-2’s ATL10 freeboard product using the Improved Buoyancy Equation. Seasonal variability in ice thickness, characterized by an increase from February to September, is more pronounced in the eastern Weddell sector, while interannual variability is more evident in the western Weddell sector. The results were compared with field data obtained between 2019 and 2022, showing a general agreement in ice thickness distributions around predominantly level ice. A decreasing trend in sea ice thickness was observed when compared to measurements from 2003 to 2017. Notably, the spring of 2021 and summer of 2022 saw significant decreases in Sea Ice Extent (SIE). Although the overall mean sea ice thickness remained unchanged, the northwestern Weddell region experienced a noticeable decrease in ice thickness.

Background: Anthropogenic climate change is causing a rise in global temperatures, with this trend projected to increase into the future. Heatwaves are associated with a rise in preventable deaths, however this association is less well understood in regions experiencing cooler climates. Methods: We used a space-time-stratified conditional Poisson (-quasi) regression analysis to assess if heatwaves were associated with all-cause mortality in Tasmania, Australia, for the period 2010–2018. Results: We found that across Tasmania, low-intensity heatwaves were relatively common, with less occurrence of severe and extreme heatwaves. We found that for all heatwave types combined, there was a rise in mortality of 8 % (RR=1.08, 95 %CI 1.01–1.16). For low-intensity heatwaves, we found mortality increased by 9 % (RR=1.09, 95 %CI 1.02–1.17). Conclusion: These results have health promotion and health protection policy and practice implications for Tasmanian healthcare services, and potentially other cooler climate regions around the world.

The particle-induced hadronic de-excitation of the Hoyle state in 12C induced by inelastic scattering in a hot and dense plasma can enhance the triple-alpha reaction rate. This prevents the production of heavy nuclei within the neutrino-driven winds of core-collapse supernovae and raises a question as to the contribution of proton-rich neutrino-driven winds as the origin of p–nuclei in the solar-system abundances. Here we study νp-process nucleosynthesis in proton-rich neutrino-driven winds relevant to the production of Mo92,94 and Ru96,98 by considering such particle-induced de-excitation. We find that the enhanced triple-alpha reaction rate induced by proton inelastic scattering can increase the production of Mo92,94 and Ru96,98 in an energetic hypernova wind model with a massive proto-neutron star although the abundances of these p–nuclei decrease in a wind model of ordinary core-collapse supernovae. The enhancement of the triple-alpha reaction rate induced by the neutron scattering hardly affects the νp-process at low temperature. We show the new result that, contrary to the results for ordinary core-collapse supernovae, the hypernova νp-process can contribute to the Galactic chemical evolution of p–nuclei regardless of the particle-induced Hoyle state de-excitation and even enhance the solar isotopic fractions of Mo92,94 and Ru96,98.

Abstract Background Evidence on the relationship between air pollution and allergic sensitisation in childhood is inconsistent, and this relationship has not been investigated in the context of smoke events that are predicted to increase with climate change. Thus, we aimed to evaluate associations between exposure in two early life periods to severe levels of particulate matter with an aerodynamic diameter

Abstract Proteostasis ensures the proper synthesis, folding, and trafficking of proteins and is required for cellular and organellar homeostasis. This network also oversees protein quality control within the cell and prevents accumulation of aberrant proteins, which can lead to cellular dysfunction and disease. For example, protein aggregates irreversibly disrupt proteostasis and can exert gain-of-function toxic effects. Although this process has been examined in detail for cytosolic proteins, how endoplasmic reticulum (ER)-tethered, aggregation-prone proteins are handled is ill-defined. To determine how a membrane protein with a cytoplasmic aggregation-prone domain is routed for ER-associated degradation (ERAD), we analyzed a new model substrate, TM-Ubc9ts. In yeast, we previously showed that TM-Ubc9ts ERAD requires Hsp104, which is absent in higher cells. In transient and stable HEK293 cells, we now report that TM-Ubc9ts degradation is largely proteasome-dependent, especially at elevated temperatures. In contrast to yeast, clipped TM-Ubc9ts polypeptides, which are stabilized upon proteasome inhibition, accumulate and are insoluble at elevated temperatures. TM-Ubc9ts cleavage is independent of the intramembrane protease RHBDL4, which clips other classes of ERAD substrates. These studies highlight an unappreciated mechanism underlying the degradation of aggregation-prone substrates in the ER and invite further work on other proteases that contribute to ERAD.

The signaling network of the unfolded protein response (UPR) adjusts the protein-folding capacity of the endoplasmic reticulum (ER) according to need. The most conserved UPR sensor, IRE1α, spans the ER membrane and activates through oligomerization. IRE1α oligomers accumulate in dynamic foci. We determined the in situ structure of IRE1α foci by cryogenic correlated light and electron microscopy combined with electron cryo-tomography and complementary immuno–electron microscopy in mammalian cell lines. IRE1α foci localized to a network of narrow anastomosing ER tubes (diameter, ~28 nm) with complex branching. The lumen of the tubes contained protein filaments, which were likely composed of arrays of IRE1α lumenal domain dimers that were arranged in two intertwined, left-handed helices. This specialized ER subdomain may play a role in modulating IRE1α signaling.

We conducted a preregistered multilaboratory project (k = 36; N = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the paradigmatic replication approach. Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result (d = 0.06). Confirmatory Bayesian meta-analyses using an informed-prior hypothesis (δ = 0.30, SD = 0.15) found that the data were 4 times more likely under the null than the alternative hypothesis. Hence, preregistered analyses did not find evidence for a depletion effect. Exploratory analyses on the full sample (i.e., ignoring exclusion criteria) found a statistically significant effect (d = 0.08); Bayesian analyses showed that the data were about equally likely under the null and informed-prior hypotheses. Exploratory moderator tests suggested that the depletion effect was larger for participants who reported more fatigue but was not moderated by trait self-control, willpower beliefs, or action orientation.

Abstract Greenhouse gas (GHG) accounting of emissions from land use, land-use change, and forestry necessarily involves consideration of landscape fire. This is of particular importance for Australia given that natural and human fire is a common occurrence, and many ecosystems are adapted to fire, and require periodic burning for plant regeneration and ecological health. Landscape fire takes many forms, can be started by humans or by lightning, and can be managed or uncontrolled. We briefly review the underlying logic of greenhouse gas accounting involving landscape fire in the 2020 Australian Government GHG inventory report. The treatment of wildfire that Australia chooses to enact under the internationally agreed guidelines is based on two core assumptions (a) that effects of natural and anthropogenic fire in Australian vegetation carbon stocks are transient and they return to the pre-fire level relatively quickly, and (b) that historically and geographically anomalous wildfires in forests should be excluded from national anthropogenic emission estimates because they are beyond human control. It is now widely accepted that anthropogenic climate change is contributing to increased frequency and severity of forest fires in Australia, therefore challenging assumptions about the human agency in fire-related GHG emissions and carbon balance. Currently, the national inventory focuses on forest fires; we suggest national greenhouse gas accounting needs to provide a more detailed reporting of vegetation fires including: (a) more detailed mapping of fire severity patterns; (b) more comprehensive emission factors; (c) better growth and recovery models from different vegetation types; (d) improved understanding how fires of different severities affect carbon stocks; and (e) improved analysis of the human agency behind the causes of emissions, including ignition types and fire-weather conditions. This more comprehensive accounting of carbon emissions would provide greater incentives to improve fire management practices that reduce the frequency, severity, and extent of uncontrolled landscape fires.