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Fire is an integral ecosystem process and a major natural source of vegetation disturbance globally. Yet at the same time, humans use and manage fire in diverse ways and for a huge range of purposes. Therefore, it is perhaps unsurprising that a central finding of the first Fire Model Intercomparison Project was simplistic representation of humans is a substantial shortcoming in the fire modules of dynamic global vegetation models (DGVMs). In response to this challenge, we present a novel, global geospatial model that seeks to capture the diversity of human–fire interactions. Empirically grounded with a global database of anthropogenic fire impacts, WHAM! (the Wildfire Human Agency Model) represents the underlying behavioural and land system drivers of human approaches to fire management and their impact on fire regimes. WHAM! is designed to be coupled with DGVMs (JULES-INFERNO in the current instance), such that human and biophysical drivers of fire on Earth, and their interactions, can be captured in process-based models for the first time. Initial outputs from WHAM! presented here are in line with previous evidence suggesting managed anthropogenic fire use is decreasing globally and point to land use intensification as the underlying reason for this phenomenon.

Abstract Fluorescent ligands have proved to be powerful tools in the study of G protein‐coupled receptors in living cells. Here we have characterized a new fluorescent ligand PSB603‐BY630 that has high selectivity for the human adenosine A2B receptor (A2BR). The A2BR appears to play an important role in regulating immune responses in the tumor microenvironment. Here we have used PSB603‐BY630 to monitor specific binding to A2BRs in M1‐ and M2‐like macrophages derived from CD14+ human monocytes. PSB603‐BY630 bound with high affinity (18.3 nM) to nanoluciferase‐tagged A2BRs stably expressed in HEK293G cells. The ligand exhibited very high selectivity for the A2BR with negligible specific‐binding detected at NLuc‐A2AR, NLuc‐A1R, or NLuc‐A3R receptors at concentrations up to 500 nM. Competition binding studies showed the expected pharmacology at A2BR with the A2BR‐selective ligands PSB603 and MRS‐1706 demonstrating potent inhibition of the specific binding of 50 nM PSB603‐BY630 to A2BR. Functional studies in HEK293G cells using Glosensor to monitor Gs‐coupled cyclic AMP responses indicated that PSB603‐BY630 acted as a negative allosteric regular of the agonist responses to BAY 60–6583. Furthermore, flow cytometry analysis confirmed that PSB603‐BY630 could be used to selectively label endogenous A2BRs expressed on human macrophages. This ligand should be an important addition to the library of fluorescent ligands which are selective for the different adenosine receptor subtypes, and will enable study of the role of A2BRs on immune cells in the tumor microenvironment.

Contested racial identity-the discrepancy between one's self-identified race and socially assigned race-is a social determinant of health and may contribute to overweight and obesity. Obesity is associated with a host of short- and long-term health conditions, including cardiovascular disease, a leading cause of death. Individuals racialized as Black, Hispanic, and Latino are at the greatest risk of obesity. Previous research indicates that experiencing interpersonal discrimination is associated with higher body mass index (BMI) in adults, and individuals with a contested racial identity are disproportionately exposed to interpersonal discrimination. However, the association between BMI and contested racial identity is unknown. This cross-sectional study measured the relationship between contested racial identity and perceived everyday discrimination on BMI in a nationally representative sample of US adults. Contested racial identity was measured with a binary variable indicating agreement between participants' self-identified race and socially assigned race. Weighted unadjusted and adjusted multiple linear regression models quantified the associations between BMI and contested racial identity with and without the mean discrimination score. Covariates included nativity status, income, education, racial identity salience, gender, and age. Among 1689 participants, 18.3% had a contested racial identity. Contested identity was associated with significantly higher BMI (β = 1.01, 95% CI = 0.06, 1.92), but the relationship was attenuated when adjusting for interpersonal discrimination, suggesting that individuals with contested identity may face a greater risk of obesity due to their disproportionately high exposure to interpersonal racial discrimination. Further research is needed to elucidate the impact of racism on BMI and obesity risk., (© 2023. W. Montague Cobb-NMA Health Institute.)

Background: Knowledge of patient lived experiences of functioning and disability is limited. This study aims to address the gap in the literature by exploring patient lived experiences of functioning and disability following lumbar discectomy., Method: A secondary analysis, reported in line with the Standards for Reporting Qualitative Research, was conducted of qualitative data exploring patient journeys following lumbar discectomy surgery (DiscJourn). Adult patients (≥ 16 years) undergoing elective or emergency primary lumbar discectomy were recruited from one National Health Service secondary care centre in the UK. Semi-structured interviews were conducted at 1-3 weeks and 1-year post surgery. Participants who completed both semi-structured interviews were eligible for the secondary analysis. Transcripts from the semi-structured interviews were analysed using interpretative phenomenological analysis (IPA). IPA involved two independent reviewers identifying themes for individual data sets followed by an iterative process involving the wider research team to identify overarching themes that represented the whole date set. Subthemes generated from the IPA were mapped against the International Classification of Functioning, Disability and Health (ICF) framework at the level of chapters, in order to ascertain the ICF's utility in capturing experiences of functioning and disability. Strategies to enhance trustworthiness of data analysis included blind coding, peer examination and debrief, declaration of pre-conceived beliefs and active reflexivity throughout the study., Results: Nine participants met the eligibility criteria and their interview transcripts were analysed. Patient lived experiences of functioning and disability were captured by three overarching themes: Immediate impact following surgery, Multiple roads to recovery over 1 year, and Functioning influenced by personal loci of control. Each theme consisted of three subthemes which were subsequently mapped onto the ICF. Three subthemes mapped to the ICF's body component, 1 to activity and participation and 3 to environment. Two subthemes themes did not map onto the ICF., Conclusion: Findings provide valuable insights into patient experiences of functioning and disability following lumbar discectomy. Convergence in experiences of functioning and disability were identified immediately following surgery. Divergence in such experiences were identified with regards to the roads to recovery over 1 year and the individuals' locus of control. Findings build on the body of literature exploring patients functioning and disability following discectomy and make recommendations for future research and clinical practice., (© 2024. The Author(s).)

Background: International agreement supports physical functioning as a key domain to measure interventions effectiveness for low back pain. Patient reported outcome measures (PROMs) are commonly used in the lumbar spinal surgery population but physical functioning is multidimensional and necessitates evaluation also with physical measures., Objective: 1) To identify outcome measures (PROMs and physical) used to evaluate physical functioning in the lumbar spinal surgery population. 2) To assess measurement properties and describe the feasibility and interpretability of physical measures of physical functioning in this population., Study Design: Two-staged systematic review and narrative synthesis., Methods: This systematic review was conducted according to a registered and published protocol. Two stages of searching were conducted in MEDLINE, EMBASE, Health & Psychosocial Instruments, CINAHL, Web of Science, PEDro and ProQuest Dissertations & Theses. Stage one included studies to identify physical functioning outcome measures (PROMs and physical) in the lumbar spinal surgery population. Stage two (inception to 10 July 2023) included studies assessing measurement properties of stage one physical measures. Two independent reviewers determined study eligibility, extracted data and assessed risk of bias (RoB) according to COSMIN guidelines. Measurement properties were rated according to COSMIN criteria. Level of evidence was determined using a modified GRADE approach., Results: Stage one included 1,101 reports using PROMs (n = 70 established in literature, n = 67 developed by study authors) and physical measures (n = 134). Stage two included 43 articles assessing measurement properties of 34 physical measures. Moderate-level evidence supported sufficient responsiveness of 1-minute stair climb and 50-foot walk tests, insufficient responsiveness of 5-minute walk and sufficient reliability of distance walked during the 6-minute walk. Very low/low-level evidence limits further understanding., Conclusions: Many physical measures of physical functioning are used in lumbar spinal surgery populations. Few have investigations of measurement properties. Strongest evidence supports responsiveness of 1-minute stair climb and 50-foot walk tests and reliability of distance walked during the 6-minute walk. Further recommendations cannot be made because of very low/low-level evidence. Results highlight promise for a range of measures, but prospective, low RoB studies are required., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kowalski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Very few drugs have the necessary physicochemical properties to cross the skin's main permeability barrier, the stratum corneum (SC), in sufficient amounts. Propylene glycol (PG) is a chemical penetration enhancer that could be included in topical formulations in order to overcome the barrier properties of the skin and facilitate the transport of drugs across it. Experiments have demonstrated that PG increases the mobility and disorder of SC lipids and may extract cholesterol from the SC, but little is known about the molecular mechanisms of drug permeation enhancement by PG. In this work, we have performed molecular dynamics (MD) simulations to investigate the molecular-level effects of PG on the structure and properties of model SC lipid bilayers. The model bilayers were simulated in the presence of PG concentrations over the range of 0-100% w/w PG, using both an all-atom and a united atom force field. PG was found to localize in the hydrophilic headgroup regions at the bilayer interface, to occupy the lipid-water hydrogen-bonding sites, and to slightly increase lipid tail disorder in a concentration-dependent manner. We showed with MD simulation that PG enhances the permeation of small molecules such as water by interacting with the bilayer interface; the results of our study may be used to guide the design of formulations for transdermal drug delivery with enhanced skin permeation, as well as topical formulations and cosmetic products.

Aim: The aim of this umbrella review was to establish which biopsychosocial factors are associated with development of chronic musculoskeletal pain., Methods: Ovid Medline, Embase, Web of Science Core Collection, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, PsycINFO, CINAHL, PEDro, PROSPERO, Google Scholar and grey literature were searched from database inception to 4th April 2023. Systematic reviews of observational prospective longitudinal studies, including populations with <3 months (not chronic) musculoskeletal pain, investigating biopsychosocial factors that contribute to development of chronic (>3 months) musculoskeletal pain. Two reviewers searched the literature, assessed risk of bias (Assessing the Methodological Quality of Systematic Reviews-2), and evaluated quality (Grading of Recommendations, Assessment, Development and Evaluation) to provide an overall statement on the certainty of evidence for each biopsychosocial factor. Data analysis was performed through random effects meta-analysis (including meta-analysis of meta-analyses where possible) and descriptive synthesis., Results: 13 systematic reviews were included comprising 185 original research studies (n = 489,644 participants). Thirty-four biopsychosocial factors are associated with development of chronic musculoskeletal pain. Meta-analyses of odds and/or likelihood ratios were possible for 25 biopsychosocial factors. There is moderate certainty evidence that smoking (OR 1.24 [95%CI, 1.14-1.34), fear avoidance (LR+ 2.11 [95%CI, 1.59-2.8]; LR- 0.5 [95%CI, 0.35-0.71]) poorer support networks (OR 1.21 [95%CI, 1.14-1.29]), lower socioeconomic status (OR 2.0 [95%CI, 1.64-2.42]), and high levels of pain (OR 5.61 [95%CI, 3.74-8.43]) are associated with development of chronic musculoskeletal pain (all P<0.001). Remaining factors are of low or very low certainty evidence., Conclusions and Relevance: There is moderate certainty evidence that smoking, fear avoidance, poorer support networks, lower socioeconomic status, and high levels of pain are associated with development of chronic musculoskeletal pain. High risk of bias was evident in most included reviews; this highlights the need for higher quality systematic reviews., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dunn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Neuropathic pain in low back-related leg pain has gained increasing interest in contemporary research. Identification of neuropathic pain in low back-related leg pain is essential to inform precision management. Diagnostic investigations are commonly used to identify neuropathic pain in low back-related leg pain; yet the diagnostic utility of these investigations is unknown. This systematic review aims to investigate the diagnostic utility of diagnostic investigations to identify neuropathic pain in low back-related leg pain., Methods and Analysis: This protocol has been designed and reported in accordance with the Cochrane Handbook for Diagnostic Test Accuracy studies, Centre for Reviews and Dissemination and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols checklist, respectively. The search strategy will involve two independent reviewers searching electronic databases (CINAHL, EMBASE, MEDLINE, Web of Science, Cochrane Library, AMED, Pedro), key journals (Spine, The Clinical Journal of Pain, PAIN, European Journal of Pain, The Journal of Pain, Musculoskeletal Science and Practice) and grey literature (British National Bibliography for report literature, OpenGrey, EThOS) from inception to 31 July 2023 to identify studies. Studies evaluating the diagnostic accuracy of diagnostic investigation to identify neuropathic pain in patients with low back-related leg pain will be eligible, studies not written in English will be excluded. The reviewers will extract the data from included studies, assess risk of bias (Quality Assessment of Diagnostic Accuracy Studies 2) and determine confidence in findings (Grading of Recommendations, Assessment, Development and Evaluation guidelines). Methodological heterogeneity will be assessed to determine if a meta-analysis is possible. If pooling of data is not possible then a narrative synthesis will be done., Ethics and Dissemination: Ethical approval is not required. Findings will be published in a peer-reviewed journal, presented at relevant conferences and shared with the Patient Partner Advisor Group at Western University, Canada., Prospero Registration Number: CRD42023438222., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)