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The underlying tenet of evidence-based decision-making in health services is assessing all the relevant evidence. Using the traditional qualitative and quantitative approaches to identifying evidence may not capture the full spectrum of factors that need to be addressed. A selective mixed-method approach may provide a comprehensive assessment of the relevant knowledge. This paper adds to the methodological literature by outlining a novel sequential, mixed-method, exploratory process for identifying evidence-based data standards that may be used for health service decision-making. The three-phase process, entitled Delphi Plus, engages peer-nominated topic-specific experts to assess all publicly available and practice-based items and, through a series of reviews, reach an evidence-based consensus on standards for decision-making. Each process phase is outlined in-depth and supplemented by practical learnings gained through its implementation. The Delphi Plus methodology provides the first comprehensive process for combining the published and practised data to develop evidence-based data standards. The routine use of Delphi Plus would provide a framework for benchmarking in health services, enabling greater monitoring and evaluation of client outcomes and improving quality care. This manuscript describes the process of implementing Delphi Plus and provides an example of data standards generated from its use, which directly inform the Australian Government's Primary Health Care 10 Year Plan. [ABSTRACT FROM AUTHOR]

Threats to the future function of forested ecosystems and stability of ecosystem service provisioning due to global change have motivated climate-adaptive forest management strategies that include various forms of tree planting termed "adaptation plantings". Despite the emergence of these strategies, less is known as to how foresters and other natural resource managers perceive or are engaged with adaptation plantings like forest assisted migration (FAM). This knowledge gap is most pronounced in regions like New England and the North Central US (hereafter, the Northeastern US) where tree planting is less common but expected to be an important forest management tool for adaptation. To address this, we surveyed 33 natural resource managers in this region actively engaged in climate change adaptation (i.e., early adopters of the practice) to assess how tree planting for adaptation is currently being pursued against the perceived barriers, opportunities, and potential future engagement with the strategy. Survey respondents overwhelmingly (93.5%) forecast increases in the future use of adaptation plantings in their work in the region, attributed to increased awareness, acceptance, and interest in the practice. Respondents expressed notable interest in strategies related to diversification and most types of FAM (e.g., assisted population expansion and assisted range expansion), but hesitancy to engage with more contentious planting types like afforestation or FAM linked to the long-distance translocation of exotic species (e.g., assisted species migration). Although examples of local enrichment plantings (i.e., non-FAM) proliferate, nineteen of the top twenty most common tree genera planted contain at least one example of FAM in the study region. The most notable barriers reported were themed as 1) biotic and abiotic, 2) information and material, and 3) policy, social, and economic factors. While most respondents report difficulty obtaining adequate planting material from nurseries (i.e., seedlings), over 80% placed orders shortly before planting (< 1 year) which likely generates difficulty in sourcing seedlings suited for a specific site and future range of environmental conditions. Although this study is limited by focusing on subset of natural resource managers who are early adopters of climate change adaptation within the region, valuable inferences into the barriers and trends are possible from this population serving on the front lines of forest adaptation. Together, these results from early adopters suggest a potentially growing need for allocating resources that engage forest stewards in adaptation planning and serve to refine policy, financing, and management practices to support this adaptation strategy in this region and beyond. [ABSTRACT FROM AUTHOR]

For a number of years research has been carried out in several centres which has demonstrated the potential benefits of 100‐m scale models for a range of meteorological phenomena. More recently, some meteorological services have started to consider seriously the operational implementation of practical hectometric models. Many, but by no means all, of the applications are likely to relate to urban areas, where the enhanced resolution has obvious benefits. This article is concerned with the issues that need to be addressed to bridge the gap between research at 100‐m scales and practical models. We highlight a number of key issues that need to be addressed, with suggestions of important avenues for future development. An overarching issue is the high computational cost of these models. Although some ideas to reduce this are presented, it will always be a serious constraint. This means that the benefits of these models over lower resolution ones, or other techniques for generating high‐resolution forecasts, will need to be clearly understood, as will the trade‐offs with resolution. We discuss issues with model dynamical cores and physics–dynamics coupling. There are a number of challenges around model parameterisations, where some of the traditional problems (e.g., convection) become easier but a number of new challenges (e.g., around surface parameterisations) appear. Observational data at these scales present a challenge and novel types of observations will need to be considered. Data assimilation will be needed for short‐range forecasts, but there is currently little knowledge of this, although some of the likely issues are clear. An ensemble approach will be essential in many cases (e.g., convection), but research is needed into ensembles at these scales and significant work on post‐processing systems is required to make the best use of models at these grid lengths. [ABSTRACT FROM AUTHOR]

A wealth of experimental and observational evidence suggests that faces have become increasingly important in the communication system of primates over evolutionary time and that both the static and moveable aspects of faces convey considerable information. Therefore, whenever there is a visual component to any multicomponent signal the face is potentially relevant. However, the role of the face is not always considered in primate multicomponent communication research. We review the literature and make a case for greater focus on the face going forward. We propose that the face can be overlooked for two main reasons: first, due to methodological difficulty. Examination of multicomponent signals in primates is difficult, so scientists tend to examine a limited number of signals in combination. Detailed examination of the subtle and dynamic components of facial signals is particularly hard to achieve in studies of primates. Second, due to a common assumption that the face contains "emotional" content. A priori categorisation of facial behavior as "emotional" ignores the potentially communicative and predictive information present in the face that might contribute to signals. In short, we argue that the face is central to multicomponent signals (and also many multimodal signals) and suggest future directions for investigating this phenomenon. [ABSTRACT FROM AUTHOR]

Adverse experiences (e.g., acute stress) and alcohol misuse can both impair skeletal muscle homeostasis, resulting in reduced protein synthesis and greater protein breakdown. Exposure to acute stress is a significant risk factor for engaging in alcohol misuse. However, little is known about how these factors together might further affect skeletal muscle health. To that end, this study investigated the effects of acute stress exposure followed by a period of binge-patterned alcohol drinking on signaling factors along mouse skeletal muscle protein synthesis (MPS) and degradation (MPD) pathways. Young adult male C57BL/6J mice participated in the Drinking in the Dark paradigm, where they received 2–4 h of access to 20% ethanol (alcohol group) or water (control group) for four days to establish baseline drinking levels. Three days later, half of the mice in each group were either exposed to a single episode of uncontrollable tail shocks (acute stress) or remained undisturbed in their home cages (no stress). Three days after stress exposure, mice received 4 h of access to 20% ethanol (alcohol) to model binge-patterned alcohol drinking or water for ten consecutive days. Immediately following the final episode of alcohol access, mouse gastrocnemius muscle was extracted to measure changes in relative protein levels along the Akt-mTOR MPS, as well as the ubiquitin-proteasome pathway (UPP) and autophagy MPD pathways via Western blotting. A single exposure to acute stress impaired Akt singling and reduced rates of MPS, independent of alcohol access. This observation was concurrent with a potent increase in heat shock protein seventy expression in the muscle of stressed mice. Alcohol drinking did not exacerbate stress-induced alterations in the MPS and MPD signaling pathways. Instead, changes in the MPS and MPD signaling factors due to alcohol access were primarily observed in non-stressed mice. Taken together, these data suggest that exposure to a stressor of sufficient intensity may cause prolonged disruptions to signaling factors that impact skeletal muscle health and function beyond what could be further induced by periods of alcohol misuse. [ABSTRACT FROM AUTHOR]

Aims: To assess the feasibility of implementing data standards in Australian primary care dietetics practices. Methods: A mixed‐methods pragmatic study of dietitians working in primary care. Using a four‐point Likert scale, participants were surveyed on their baseline use of the 45 business and 33 clinical evidenced‐based data standards. The content validity index and kappa statistic for each standard were calculated with a kappa statistic of 0.60–0.74 considered 'Good' and > 0.74 'Excellent'. After 4 weeks of assessment, dietitians were surveyed on the feasibility of implementing each standard and standards in total. Qualitative feedback on enablers and barriers to implementing standards was gathered and triangulated with interviews with select participants. Results: Forty‐five dietitians from every Australian state and territory completed both surveys (response rate: 100%). At baseline, 24% of business and 79% of clinical standards were rated 'Good' or 'Excellent' for current usage. The feasibility of implementing standards was rated 'Good' or 'Excellent for 86% of the business and 97% of the clinical standards. Software, training and time limitations are enablers and barriers to implementing standards. Conclusion: Embedding data standards within dietetics practices are feasible and have broad applicability for assessing outcomes of care. [ABSTRACT FROM AUTHOR]

In this study, the moist buffering halo region of shallow maritime cumulus clouds is systematically investigated using large eddy simulations with various grid resolutions and numerical choices. Autocorrelation analyses of cloud liquid water and relative humidity suggest a converged size of 200–300 m for moist patches outside clouds when the model resolution is below 50 m, but may overestimate this size due to noncloudy moist regions. Based on a composite analysis, the structure of the moist halo immediately outside individual clouds is examined. It is found that, regardless of model resolution, the distribution of relative humidity in the halo region does not depend on cloud size, but on the real distance away from the cloud boundary, indicating some size‐independent length scales are responsible for the halo formation. The relative humidity decays with distance more quickly with finer horizontal resolution, which is possibly related to the model resolution dependence of the cloud spectrum. The halo size near the cloud base is larger than that within the cloud layer and this feature is robust across all simulations. Further analyses of backward and forward Lagrangian trajectories originating from the moist halo region reveal the possible role for subcloud coherent structures in cloud‐base halo formation. Possible mechanisms explaining cloud halo sizes and associated length scales are discussed. [ABSTRACT FROM AUTHOR]

We present new spectroscopic and photometric follow-up observations of the known sample of extreme coronal line-emitting galaxies (ECLEs) identified in the Sloan Digital Sky Survey (SDSS). With these new data, observations of the ECLE sample now span a period of two decades following their initial SDSS detections. We confirm the non-recurrence of the iron coronal line signatures in five of the seven objects, further supporting their identification as the transient light echoes of tidal disruption events (TDEs). Photometric observations of these objects in optical bands show little overall evolution. In contrast, mid-infrared (MIR) observations show ongoing long-term declines consistent with power-law decay. The remaining two objects had been classified as active galactic nuclei (AGNs) with unusually strong coronal lines rather than being TDE related, given the persistence of the coronal lines in earlier follow-up spectra. We confirm this classification, with our spectra continuing to show the presence of strong, unchanged coronal line features and AGN-like MIR colours and behaviour. We have constructed spectral templates of both subtypes of ECLE to aid in distinguishing the likely origin of newly discovered ECLEs. We highlight the need for higher cadence, and more rapid, follow-up observations of such objects to better constrain their properties and evolution. We also discuss the relationships between ECLEs, TDEs, and other identified transients having significant MIR variability. [ABSTRACT FROM AUTHOR]

Regular exercise has numerous health benefits, but the human population displays significant variability in exercise participation. Rodent models, such as voluntary wheel running (VWR) in rats, can provide insight into the underlying mechanisms of exercise behavior and its regulation. In this study, we focused on the role of estrogen on VWR in female rats. Female rats run more than males, and we aimed to determine to what extent running levels in females were regulated by estrogen signaling. The running behavior of rats (duration, speed, and total distance run) was measured under normal physiological conditions, ovariectomy (OVX), and estrogen replacement in an OVX background. Results show cyclic variations in running linked to the estrous cycle. Ovariectomy markedly reduced running and eliminated the cyclic pattern. Estrogen replacement through estradiol benzoate (EB) injections and osmotic minipumps reinstated running activity to pre-OVX levels and restored the cyclic pattern. Importantly, individual differences and ranking are preserved such that high versus low runners before OVX remain high and low runners after treatment. Further analysis revealed that individual variation in running distance was primarily caused by rats running different speeds, but rats also varied in running duration. However, it is noteworthy that this model also displays features distinct from estrogen-driven running behavior under physiological conditions, notably a delayed onset and a broader duration of running activity. Collectively, this estrogen causality VWR model presents a unique opportunity to investigate sex-specific mechanisms that control voluntary physical activity. [ABSTRACT FROM AUTHOR]

Introduction: Patient education is an essential element of the treatment pathway. Augmented reality (AR), with disease simulations and three-dimensional visuals, offers a developing approach to patient education. We aim to determine whether this tool can increase patient understanding of their disease and post-visit satisfaction in comparison to current standard of care (SOC) educational practices in a randomized control study. Methods: Our single-site study consisted of 100 patients with initial diagnoses of kidney masses or stones randomly enrolled in the AR or SOC arm. In the AR arm, a physician used AR software on a tablet to educate the patient. SOC patients were educated through traditional discussion, imaging, and hand-drawn illustrations. Participants completed pre-.and post-physician encounter surveys adapted from the Press Ganey® patient questionnaire to assess understanding and satisfaction. Their responses were evaluated in the Readability Studio® and analyzed to quantify rates of improvement in self-reported understanding and satisfaction scores. Results: There was no significant difference in participant education level (P = 0.828) or visit length (27.6 vs. 25.0 min, P = 0.065) between cohorts. Our data indicate that the rate of change in pre-.to post-visit self-reported understanding was similar in each arm (P ≥ 0.106 for all responses). The AR arm, however, had significantly higher patient satisfaction scores concerning the educational effectiveness and understanding of images used during the consultation (P < 0.05). Conclusions: While AR did not significantly increase self-reported patient understanding of their disease compared to SOC, this study suggests AR as a potential avenue to increase patient satisfaction with educational tools used during consultations. [ABSTRACT FROM AUTHOR]

Background: Childhood malnutrition can have devastating consequences on health, behavior, and cognition. Edible insects are sustainable low cost high protein and iron nutritious foods that can prevent malnutrition. However, it is unclear whether insect-based diets may help prevent changes to brain neurochemistry associated with malnutrition. Materials and Methods: Weanling male Sprague–Dawley rats were malnourished by feeding a low protein-iron diet (LPI, 5% protein and ∼2 ppm Fe) for 3 weeks or nourished by feeding a sufficient protein-iron diet (SPI, 15% protein 20 ppm FeSO4) for the duration of the study. Following 3 weeks of LPI diet, three subsets of the malnourished rats were placed on repletion diets supplemented with cricket, palm weevil larvae, or the SPI diet for 2 weeks, while the remaining rats continued the LPI diet for an additional 2 weeks. Monoamine-related neurochemicals (e.g. serotonin (5-HT), dopamine (DA), norepinephrine) and select monoamine metabolites were measured in the hypothalamus, hippocampus, striatum, and prefrontal cortex using Ultra High-Performance Liquid Chromatography. Results: Five weeks of LPI diets disrupted brain monoamines, most notable in the hypothalamus. Two weeks supplementation with cricket and palm weevil larvae diets prevented changes to measures of 5-HT and DA turnover in the hippocampus and hypothalamus. Moreover, these insect diets prevented the malnutrition-induced imbalance of 5-HT and DA metabolites in the hippocampus, striatum, and hypothalamus. Conclusion: Edible insects such as cricket and palm weevil larvae could be sustainable nutrition intervention to prevent behavioral and cognitive impairment associated abnormal brain monoamine activities that results from early life malnutrition. [ABSTRACT FROM AUTHOR]

Tree planting is increasingly being adopted as a strategy to address global change, including mitigation, adaptation, and restoration. Although reforestation has long been central to forest management, the desired outcomes of traditional and emerging tree-planting strategies face barriers linked to a lack of ecological diversity in forest nurseries. In the present article, we outline how insufficient diversity in nursery seedlings among species, genotypes, and stock types has impeded and will continue to hinder the implementation of diverse ecological or climate-suitable planting targets, now and into the future. To support this, we demonstrate disparities in seedling diversity among nursery inventories, focusing on the northern United States. To overcome these challenges, we recommend avenues for improving policy and financing, informational resources and training, and research and monitoring. Absent these advances, current seedling production and practices will fall short of ambitious tree-planting goals proposed for forest restoration and global change mitigation and adaptation. [ABSTRACT FROM AUTHOR]

Aim: To identify minimum reporting standards for assessing the processes and outcomes of Australian primary care dietetics practice. Methods: A sequential, mixed‐method, exploratory process with peer‐nominated Australian 'thought leaders'. A literature review was undertaken to identify possible standards, followed by semi‐structured qualitative interviews with thought leaders. Content analysis was used to identify a comprehensive group of items that could inform evidence‐based reporting standards. Two rounds of a modified Delphi survey were conducted with the same thought leaders to seek consensus on the most relevant items. Individual items were analysed for content validity, and those with a rating of excellent item‐content validity (index >0.78) were included as evidenced‐based standards for primary care practice. Results: Twenty‐six thought leaders (response rate: 87%) from all mainland Australian states completed a qualitative interview and two rounds of modified‐Delphi consensus surveys. Items were identified and categorised into three domains: business, clinical, and implementation. Content analysis identified 216 items published or used in practice by the thought leaders. After two rounds of consensus review, 97 items (45 business, 33 clinical, and 19 implementation) achieved excellent consensus ratings. Combining these items into a standardised tool, the scale‐content validity index average was >0.90, which is considered excellent content validity. Conclusions: This study has identified minimum reporting standards for evidence‐based process and outcome assessments in primary care dietetics practice in Australia. Incorporating such standards into a standardised tool could enable benchmarking across the dietetics workforce and contribute to a broader understanding of the dietetic impact on public health. [ABSTRACT FROM AUTHOR]

Introduction: Sedentary lifestyles have reached epidemic proportions worldwide. A growing body of literature suggests that exposures to adverse experiences (e.g., psychological traumas) are a significant risk factor for the development of physically inactive lifestyles. However, the biological mechanisms linking prior stress exposure and persistent deficits in physical activity engagement remains poorly understood. Methods: The purpose of this study was twofold. First, to identify acute stress intensity thresholds that elicit long-term wheel running deficits in rats. To that end, young adult male rats were exposed to a single episode of 0, 50, or 100 uncontrollable tail shocks and then given free access to running wheels for 9 weeks. Second, to identify stress-induced changes to central monoamine neurotransmitters and peripheral muscle physiology that may be maladaptive to exercise output. For this study, rats were either exposed to a single episode of uncontrollable tail shocks (stress) or left undisturbed in home cages (unstressed). Eight days later, monoamine-related neurochemicals were quantified by ultrahigh performance liquid chromatography (UHPLC) across brain reward, motor, and emotion structures immediately following a bout of graded treadmill exercise controlled for duration and intensity. Additionally, protein markers of oxidative stress, inflammation, and metabolic activity were assessed in the gastrocnemius muscle by Western blot. Results: For experiment 1, stress exposure caused a shock number-dependent two to fourfold decrease in wheel running distance across the entire duration of the study. For experiment 2, stress exposure curbed an exercise-induced increase of dopamine (DA) turnover measures in the prefrontal cortex and hippocampus, and augmented serotonin (5HT) turnover in the hypothalamus and remaining cortical area. However, stress exposure also caused several monoaminergic changes independent of exercise that could underlie impaired motivation for physical activity, including a mild dopamine deficiency in the striatal area. Finally, stress potently increased HSP70 and lowered SOD2 protein concentrations in the gastrocnemius muscle, which may indicate prolonged oxidative stress. Discussion: These data support some of the possible central and peripheral mechanisms by which exposure to adverse experiences may chronically impair physical activity engagement. [ABSTRACT FROM AUTHOR]

Purpose: Small molecule inhibitors that target oncogenic driver kinases are an important class of therapies for non-small cell lung cancer (NSCLC) and other malignancies. However, these therapies are not without their challenges. Each inhibitor works on only a subset of patients, the pharmacokinetics of these inhibitors is variable, and these inhibitors are associated with significant side effects. Many of these inhibitors lack non-invasive biomarkers to confirm pharmacodynamic efficacy, and our understanding of how these inhibitors block cancer cell growth remains incomplete. Limited clinical studies suggest that early (< 2 weeks after start of therapy) changes in tumor glucose consumption, measured by [18F]FDG PET imaging, can predict therapeutic efficacy, but the scope of this strategy and functional relevance of this inhibition of glucose consumption remains understudied. Here we demonstrate that early inhibition of glucose consumption as can be measured clinically with [18F]FDG PET is a consistent phenotype of efficacious targeted kinase inhibitors and is necessary for the subsequent inhibition of growth across models of NSCLC. Methods: We tested nine NSCLC cell lines (A549, H1129, H1734, H1993, H2228, H3122, H460, HCC827, and PC9 cells) and ten targeted therapies (afatinib, buparlisib, ceritinib, cabozantinib, crizotinib, dovitinib, erlotinib, ponatinib, trametinib, and vemurafenib) across concentrations ranging from 1.6 nM to 5 µM to evaluate whether these inhibitors block glucose consumption at 24-h post-drug treatment and cell growth at 72-h post-drug treatment. We overexpressed the facilitative glucose transporter SLC2A1 (GLUT1) to test the functional connection between blocked glucose consumption and cell growth after treatment with a kinase inhibitor. A subset of these inhibitors and cell lines were studied in vivo. Results: Across the nine NSCLC cell lines, ten targeted therapies, and a range of inhibitor concentrations, whether a kinase inhibitor blocked glucose consumption at 24-h post-drug treatment strongly correlated with whether that inhibitor blocked cell growth at 72-h post-drug treatment in cell culture. These results were confirmed in vivo with [18F]FDG PET imaging. GLUT1 overexpression blocked the kinase inhibitors from limiting glucose consumption and cell growth. Conclusions: Our results demonstrate that the early inhibition of lung cancer glucose consumption in response to a kinase inhibitor is a strong biomarker of and is often required for the subsequent inhibition of cell growth. Early inhibition of glucose consumption may provide complementary information to other biomarkers in determining whether a drug will effectively limit tumor growth. [ABSTRACT FROM AUTHOR]

Introduction: The American Cancer Society estimates 79,000 individuals will be diagnosed with kidney cancer in 2022, most of which are initially found as small renal masses (SRMs). Proper management of SRM patients includes careful evaluation of risk factors such as medical comorbidities and renal function. To investigate the importance of these risk factors, we examined their effect on crossover to delayed intervention (DI) and overall survival (OS) in patients undergoing active surveillance (AS) for SRMs. Methods: This is an Institutional Review Board-approved retrospective analysis of AS patients presented at kidney tumor conferences with SRMs between 2007 and 2017. Univariable and multivariable logistic regression analyses were performed to determine how factors including estimated glomerular filtration rate (eGFR), diabetes, and chronic kidney disease are associated with DI and OS. Results: A total of 111 cases were reviewed. In general, AS patients were elderly and had significant comorbidities. On univariate analysis, intervention was more likely to occur in patients with a younger age (P = 0.01), better kidney function (P = 0.01), and higher tumor growth rates (GRs) (P = 0.02). Higher eGFR was associated with better survival (P = 0.03), while higher tumor GRs (P = 0.014), greater Charlson Comorbidity Index (P = 0.01), and larger tumors (P = 0.01) were associated with worse OS. Of the comorbidities, diabetes was found to be an independent predictor of worse OS (P= 0.01). Conclusions: Patient-level factors - such as diabetes and eGFR - are associated with the rate of DI and OS among SRM patients. Consideration of these factors may facilitate better AS protocols and improve patient outcomes for those with SRMs. [ABSTRACT FROM AUTHOR]

Alterations in global climate via extreme precipitation will have broadscale implications on ecosystem functioning. The increased frequency of drought, coupled with heavy, episodic rainfall are likely to generate impacts on biotic and abiotic processes across aquatic and terrestrial ecosystems. Despite the demonstrated shifts in global precipitation, less is known how extreme precipitation interacts with biophysical factors to control future demographic processes, especially those sensitive to climate extremes such as organismal recruitment and survival. We utilized a field‐based precipitation manipulation experiment in 0.1 ha forest canopy openings to test future climate scenarios characterized by extreme precipitation on temperate tree seedling survival. The effects of planting seedbeds (undisturbed leaf litter/organic material vs. scarified, exposed mineral soils), seedling ontogeny, species, and functional traits were examined against four statistically defined precipitation scenarios. Results indicated that seedlings grown within precipitation treatments characterized by heavy, episodic rainfall preceded by prolonged drying responded similarly to drought treatments lacking episodic inputs. Moreover, among all treatment conditions tested, scarified seedbeds most strongly affected seedling survivorship (odds ratio 6.9). Compared with any precipitation treatment, the effect size (predicted probabilities) of the seedbed was more than twice as important in controlling seedling survivorship. However, the interaction between precipitation and seedbed resulted in a 27.9% improvement in survivorship for moisture‐sensitive species. Seedling sensitivity to moisture was variable among species, and most closely linked with functional traits such as seed mass. For instance, under dry moisture regimes, survivorship increased linearly with seed mass (log transformed; adjusted R2 = 0.72, p < 0.001), yet no relationship was apparent under wet moisture regimes. Although precipitation influenced survival, extreme rainfall events were not enough to offset moisture deficits nor provide a rescue effect under drought conditions. The relationships reported here highlight the importance of plant seedbeds and species (e.g., functional traits) as edaphic and biotic controls that modify the influence of extreme future precipitation on seedling survival in temperate forests. Finally, we demonstrated the biophysical factors that were most influential to early forest development and that may override the negative effects of increasingly variable precipitation. This work contributes to refinements of species distribution models and can inform reforestation strategies intended to maintain biodiversity and ecosystem function under increasing climate extremes. [ABSTRACT FROM AUTHOR]

Squamous cell lung cancer maintains its growth through elevated glucose consumption, but selective glucose consumption inhibitors are lacking. Here, we discovered using a high-throughput screen new compounds that block glucose consumption in three squamous cell lung cancer cell lines and identified 79 compounds that block glucose consumption in one or more of these cell lines. Based on its ability to block glucose consumption in all three cell lines, pacritinib, an inhibitor of FMS Related Receptor Tyrosine Kinase 3 (FLT3) and Janus Kinase 2 (JAK2), was further studied. Pacritinib decreased glucose consumption in squamous cell lung cancer cells in cell culture and in vivo without affecting glucose consumption in healthy tissues. Pacritinib blocked hexokinase activity, and Hexokinase 1 and 2 mRNA and protein expression. Overexpression of Hexokinase 1 blocked the ability of pacritinib to inhibit glucose consumption in squamous cell lung cancer cells. Overexpression of FLT3 but not JAK2 significantly increased glucose consumption and blocked the ability of pacritinib to inhibit glucose consumption in squamous cell lung cancer cells. Additional FLT3 inhibitors blocked glucose consumption in squamous cell lung cancer cells. Our study identifies FLT3 inhibitors as a new class of inhibitors that can block glucose consumption in squamous cell lung cancer. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an autoimmune disease driven by lymphocyte activation against myelin autoantigens in the central nervous system leading to demyelination and neurodegeneration. The deoxyribonucleoside salvage pathway with the rate‐limiting enzyme deoxycytidine kinase (dCK) captures extracellular deoxyribonucleosides for use in intracellular deoxyribonucleotide metabolism. Previous studies have shown that deoxyribonucleoside salvage activity is enriched in lymphocytes and required for early lymphocyte development. However, specific roles for the deoxyribonucleoside salvage pathway and dCK in autoimmune diseases such as MS are unknown. Here we demonstrate that dCK activity is necessary for the development of clinical symptoms in the MOG35–55 and MOG1–125 experimental autoimmune encephalomyelitis (EAE) mouse models of MS. During EAE disease, deoxyribonucleoside salvage activity is elevated in the spleen and lymph nodes. Targeting dCK with the small molecule dCK inhibitor TRE‐515 limits disease severity when treatments are started at disease induction or when symptoms first appear. EAE mice treated with TRE‐515 have significantly fewer infiltrating leukocytes in the spinal cord, and TRE‐515 blocks activation‐induced B and T cell proliferation and MOG35–55‐specific T cell expansion without affecting innate immune cells or naïve T and B cell populations. Our results demonstrate that targeting dCK limits symptoms in EAE mice and suggest that dCK activity is required for MOG35–55‐specific lymphocyte activation‐induced proliferation. [ABSTRACT FROM AUTHOR]

Stress-induced abnormalities in gut monoamine levels (e.g., serotonin, dopamine, norepinephrine) have been linked to gastrointestinal (GI) dysfunction, as well as the worsening of symptoms in GI disorders. However, the influence of stress on changes across the entire intestinal monoamine biogeography has not been well-characterized, especially in the days following stress exposure. Therefore, the aim of this study was to comprehensively assess changes to monoamine neurochemical signatures across the entire rat intestinal tract days after exposure to an acute stressor. To the end, adult male F344 rats were subjected to an episode of unpredictable tail shocks (acute stress) or left undisturbed. Forty-eight hours later rats were euthanized either following a 12 h period of fasting or 30 min of food access to evaluate neurochemical profiles during the peri- and early postprandial periods. Monoamine-related neurochemicals were measured via UHPLC in regions of the small intestine (duodenum, jejunum, ileum), large intestine (cecum, proximal colon, distal colon), cecal contents, fecal contents, and liver. The results suggest a relatively wide-spread increase in measures of serotonin activity across intestinal regions can be observed 48 h after exposure to acute stress, however some evidence was found supporting localized differences in serotonin metabolization. Moreover, acute stress exposure reduced catecholamine-related neurochemical concentrations most notably in the ileum, and to a lesser extent in the cecal contents. Next, stress-related fecal serotonin concentrations were consistent with intestinal profiles. However, fecal dopamine was elevated in association with stress, which did not parallel findings in any other intestinal area. Finally, stress exposure and the food access period together only had minor effects on intestinal monoamine profiles. Taken together, these data suggest nuanced differences in monoaminergic profiles exist across intestinal regions the days following exposure to an acute stressor, highlighting the importance of assessments that consider the entire intestinal tract biogeography when investigating stressrelated biological outcomes that may be relevant to GI pathophysiology. [ABSTRACT FROM AUTHOR]

There is increasing momentum to implement conservation and management approaches that adapt forests to climate change so as to sustain ecosystem functions. These range from actions designed to increase the resistance of current composition and structure to negative impacts to those designed to transition forests to substantially different characteristics. A component of many adaptation approaches will likely include assisted migration of future climate‐adapted tree species or genotypes. While forest‐assisted migration (FAM) has been discussed conceptually and examined experimentally for almost a decade, operationalizing FAM (i.e., routine use in forest conservation and management projects) lags behind the acceptance of the need for climate adaptation. As the vulnerability of forest ecosystems in climate change increases, FAM may need to become an integral management tool to reduce long‐term risks to ecosystem function, despite real and perceived barriers for its implementation. Here we discuss the concept of operational‐scale FAM and why it remains a controversial, not yet widely adopted component of climate adaptation. We present three case studies of operational‐scale FAM to illustrate how the practice can be approached pragmatically within an adaptation framework despite the barriers to acceptance. Finally, we discuss a path toward advancing the wide use of operational‐scale FAM. [ABSTRACT FROM AUTHOR]

Ambiguity in communicative signals may lead to misunderstandings and thus reduce the effectiveness of communication, especially in unpredictable interactions such as between closely matched rivals or those with a weak social bond. Therefore, signals used in these circumstances should be less ambiguous, more stereotyped and more intense. To test this prediction, we measured facial movements of crested macaques (Macaca nigra) during spontaneous social interaction, using the Facial Action Coding System for macaques (MaqFACS). We used linear mixed models to assess whether facial movement intensity and variability varied according to the interaction outcome, the individuals' dominance relationship and their social bond. Movements were least intense and most variable in affiliative contexts, and more intense in interactions between individuals who were closely matched in terms of dominance rating. We found no effect of social bond strength. Our findings provide evidence for a reduction in ambiguity of facial behaviour in risky social situations but do not demonstrate any mitigating effect of social relationship quality. The results indicate that the ability to modify communicative signals may play an important role in navigating complex primate social interactions. This article is part of the theme issue 'Cognition, communication and social bonds in primates'. [ABSTRACT FROM AUTHOR]

This account of Vera Bacskai's contribution to European urban history after 1990 is a personal narrative, written by a friend and collaborator. It argues that her role was multi-dimensional. It was founded on her major publications on Budapest and small towns, shedding a crucial East Central European light on European urbanization. It was underpinned by her participation in various international projects like the EU TEMPUS programme which created strong institutional bonds with Western universities as well as opportunities for Hungarian students through exchange programmes, international workshops and the like. Not least, she was a strong pillar in the construction of the European Association for Urban History. When she joined the committee in 1991, it was still an embryonic body. In 1996, she organized the successful and important Budapest conference. When she retired from EAUH in 2004, its conferences were attracting many hundreds of researchers, from across Europe and beyond. [ABSTRACT FROM AUTHOR]

Genome editing in non-human primates with a PCSK9-targeted meganuclease lowers cholesterol levels. Clinical translation of in vivo genome editing to treat human genetic diseases requires thorough preclinical studies in relevant animal models to assess safety and efficacy. A promising approach to treat hypercholesterolemia is inactivating the secreted protein PCSK9, an antagonist of the LDL receptor. Here we show that single infusions in six non-human primates of adeno-associated virus vector expressing an engineered meganuclease targeting PCSK9 results in dose-dependent disruption of PCSK9 in liver, as well as a stable reduction in circulating PCSK9 and serum cholesterol. Animals experienced transient, asymptomatic elevations of serum transaminases owing to the formation of T cells against the transgene product. Vector DNA and meganuclease expression declined rapidly, leaving stable populations of genome-edited hepatocytes. A second-generation PCSK9-specific meganuclease showed reduced off-target cleavage. These studies demonstrate efficient, physiologically relevant in vivo editing in non-human primates, and highlight safety considerations for clinical translation. [ABSTRACT FROM AUTHOR]

Objective: To examine the performance of Leibovich score versus GRade, Age, Nodes, and Tumor score in predicting disease recurrence in renal cell carcinoma. Methods: In total, 7653 patients diagnosed with renal cell carcinoma from 2010 to 2018 were captured in the nationwide DaRenCa database; 2652 underwent radical or partial nephrectomy and had full datasets regarding the GRade, Age, Nodes, and Tumor score and Leibovich score. Discrimination was assessed with a Cox regression model. The results were evaluated with concordance index analysis. Results: Median follow‐up was 40 months (interquartile range 24–56). Recurrence occurred in 17%, and 15% died. A significant proportion of patients (36%) had missing data for the calculation of the Leibovich score. Among 1957 clear cell renal cell carcinoma patients the distribution of GRade, Age, Nodes, and Tumor score of 0, 1, 2, or 3/4 was 21%, 56%, 21% and 1.4%, respectively, and for Leibovich score of low/intermediate/high this was 47%, 36% and 18%, respectively. A similar distribution was seen in 655 non‐clear cell patients. Both Leibovich and GRade, Age, Nodes, and Tumor scores performed well in predicting outcomes for the favorable patient risk groups. The Leibovich score was better at predicting recurrence‐free survival (concordance index 0.736 versus 0.643), but not overall survival (concordance index 0.657 versus 0.648). Similar results were obtained in non‐clear cell renal cell carcinoma. Conclusion: GRade, Age, Nodes, and Tumor and Leibovich scores were validated in clear cell and non‐clear cell renal cell carcinoma. Leibovich score outperformed the GRade, Age, Nodes, and Tumor score in predicting recurrence‐free survival and should remain the standard approach to risk stratify patients during follow‐up when all data are available. [ABSTRACT FROM AUTHOR]

Proteins perform many essential functions in biological systems and can be successfully developed as bio-therapeutics. It is invaluable to be able to predict their properties based on a proposed sequence and structure. In this study, we developed a novel generalizable deep learning framework, LM-GVP, composed of a protein Language Model (LM) and Graph Neural Network (GNN) to leverage information from both 1D amino acid sequences and 3D structures of proteins. Our approach outperformed the state-of-the-art protein LMs on a variety of property prediction tasks including fluorescence, protease stability, and protein functions from Gene Ontology (GO). We also illustrated insights into how a GNN prediction head can inform the fine-tuning of protein LMs to better leverage structural information. We envision that our deep learning framework will be generalizable to many protein property prediction problems to greatly accelerate protein engineering and drug development. [ABSTRACT FROM AUTHOR]

An important practical problem is to understand the depth to which pollutants will be mixed in the boundary layer over cities. This is particularly important shortly after sunrise on clear days when the mixed layer is often shallow and there may be large emissions from rush‐hour traffic. The 100 m scale NWP models currently under development have the potential to represent the boundary‐layer structure over cities on neighbourhood scales for air quality and other applications. Here we describe work with Met Office Unified Model (MetUM) configurations with grid lengths of 100, 50 and 25 m to represent the morning growth of a clear convective boundary layer over London compared to observations. All three models explicitly represent the convective overturning although it is not as well resolved at 100 m and this is a particular problem early in the day. It is found that in both the observations and in the models that the depth to which aerosol is mixed up into the model from the surface is lower than the turbulence mixed‐layer depth as measured from the vertical velocity variance. We present an analysis in the 25 m model that shows that the reason for the discrepancy is that the aerosol is transported upwards from the surface by convective plumes whereas further up there is wave motion which does not transport aerosol. The signature for these two layers can be seen both in the 25 m model and in the observations. We discuss the representation of these effects in the coarser‐resolution 100 and 55 m models and also possible mechanisms for the generation of the waves. [ABSTRACT FROM AUTHOR]

Background: Dietitians working in private practices in primary settings provide nutrition care to support individuals with the prevention and management of chronic disease. A better understanding of the type and usage of data collected by dietitians in this setting may provide insights to optimise the effectiveness and impact of the workforce. The present study explored the perceptions of leading Australian private practice dietitians on the collection and usage of data in their practice. Methods: A qualitative descriptive study of Australian private practice dietitians, recruited by snowball sampling, was conducted on their perceptions and attitudes towards collecting and using data. Data were collected by semi‐structured interviews and all interview data were thematically analysed. Results: Twenty‐three dietitians participated. Five themes emerged: (i) collecting data is challenging, nuanced, unclearly defined and therefore not routinely carried out; (ii) consistent data collection processes are impeded by the diversity of practise and practices; (iii) business‐related data collection is essential for sustainable dietetic services; (iv) clinical outcomes are fundamental to dietetic services; and (v) standardised, integrated systems are needed to enable routine data collection and synthesis. Conclusions: Our findings demonstrate the rudimentary role business acumen has in practice viability and provides evidence to potentially re‐shape the future of dietetic education in Australia. Private practice dietitians may benefit from tools and training that enable consistent collection of data about their services. Such data could enable benchmarking across the workforce and contribute to a broader understanding of dietetic impact on public health. Highlights: A qualitative descriptive study is provided of 'thought leading' dietitians on their perceptions of outcome data collection.Our findings demonstrate the rudimentary role business acumen has in practice viability.Private practice dietitians may benefit from tools and training that enable consistent collection of data about their services.Calls have been made for such training to be incorporated into the dietetic curriculum.Standardised assessments may enable benchmarking across the workforce and contribute to a broader understanding of dietetic impact on public health. [ABSTRACT FROM AUTHOR]