Transitioning to home and beyond following stroke: a prospective cohort study of outcomes and needs.

INTRODUCTION: Understanding of the needs of people with stroke at hospital discharge and in the first six-months is limited. This study aim was to profile and document the needs of people with stroke at hospital discharge to home and thereafter. METHODS: A prospective cohort study recruiting individuals with stroke, from three hospitals, who transitioned home, either directly, through rehabilitation, or with early supported discharge teams. Their outcomes (global-health, cognition, function, quality of life, needs) were described using validated questionnaires and a needs survey, at 7-10 days, and at 3-, and 6-months, post-discharge. RESULTS: 72 patients were available at hospital discharge; mean age 70 (SD 13); 61% female; median NIHSS score of 4 (IQR 0-20). 62 (86%), 54 (75%), and 45 (63%) individuals were available respectively at each data collection time-point. Perceived disability was considerable at hospital discharge (51% with mRS ≥ 3), and while it improved at 3-months, it increased thereafter (35% with mRS ≥ 3 at 6-months). Mean physical health and social functioning were "fair" at hospital discharge and ongoing; while HR-QOL, although improved over time, remained impaired at 6-months (0.69+/-0.28). At 6-months cognitive impairment was present in 40%. Unmet needs included involvement in transition planning and care decisions, with ongoing rehabilitation, information, and support needs. The median number of unmet needs at discharge to home was four (range:1-9), and three (range:1-7) at 6-months. CONCLUSION: Stroke community reintegration is challenging for people with stroke and their families, with high levels of unmet need. Profiling outcomes and unmet needs for people with stroke at hospital-to-home transition and onwards are crucial for shaping the development of effective support interventions to be delivered at this juncture. ISRCTN REGISTRATION: 02/08/2022; ISRCTN44633579.

Regulation of inositol 5-phosphatase activity by the C2 domain of SHIP1 and SHIP2.

SHIP1, an inositol 5-phosphatase, plays a central role in cellular signaling. As such, it has been implicated in many conditions. Exploiting SHIP1 as a drug target will require structural knowledge and the design of selective small molecules. We have determined apo, and magnesium and phosphate-bound structures of the phosphatase and C2 domains of SHIP1. The C2 domains of SHIP1 and the related SHIP2 modulate the activity of the phosphatase domain. To understand the mechanism, we performed activity assays, hydrogen-deuterium exchange mass spectrometry, and molecular dynamics on SHIP1 and SHIP2. Our findings demonstrate that the influence of the C2 domain is more pronounced for SHIP2 than SHIP1. We determined 91 structures of SHIP1 with fragments bound, with some near the interface between the two domains. We performed a mass spectrometry screen and determined four structures with covalent fragments. These structures could act as starting points for the development of potent, selective probes.

Difficult-to-express antigen generation through a co-expression and disassociation methodology.

Extracellular domain (ECD) antigens are crucial components for antibody discovery, in vitro assays, and epitope mapping during therapeutical antibody development. Oftentimes, those antigens are difficult to produce while retaining the biologic function/activity upon extracellular secretion in commonly used expression systems. We have developed an effective method to cope with the challenge of generating quality antigen ECDs. In this method, a monoclonal antibody (Mab) or antibody fragment antigen-binding (Fab) region acts as a "chaperone" to stabilize the antigen ECD through forming an antibody:antigen complex. This methodology includes transient co-expression of the complex in Chinese hamster ovary cells and then dissociation of the purified complex into individual components by low pH treatment in the presence of arginine. The antigen is then separated from the chaperone on a preparative size exclusion chromatography (pSEC) followed by an optional affinity chromatography process to remove residual Mab or Fab. We demonstrate this co-expression/disassociation methodology on two difficult-to-express antigen ECDs from cluster-of-differentiation/cytokine family and were successful in producing stable, biologically active antigens when the common methods using Histidine-tagged and/or Fc-fused protein failed. This can be applied as a general approach for antigen production if a Mab or binding partner is available.

Communicating medical information with Aboriginal patients: lessons learned from GPs and GP registrars in Aboriginal primary health care.

BACKGROUND: Aboriginal culture stands as the oldest continuous culture in the world. It gives paramount importance to a harmonious balance between personal connections to the body, spirit, and mind, as well as collective relationships with family, land, and community, integral to the wellbeing of Aboriginal people. However, obstacles can emerge for patients due to language barriers, cultural differences, or a historical lack of trust in the healthcare system. The establishment of Aboriginal Community Controlled Health Organisations (ACCHOs) has undoubtedly improved the healthcare experience for Aboriginal patients, yet there is limited research on the specific approaches utilised by general practitioners (GPs) working in these clinics. METHODS: Twelve semi-structured interviews were conducted with two groups of GPs working in Aboriginal health. Each GP was presented with three scenarios and asked questions related to each scenario. Braun and Clarke's method of thematic analysis was applied to transcribed interviews. RESULTS: Patient-doctor relationship, health literacy, and engagement with the health system emerged as key factors influencing communication with Aboriginal patients. Experienced GPs, despite differing clinical backgrounds, shared concise yet similar ideas to their less experienced counterparts. Notably, experienced GPs prioritised non-medical conversations and mindful body language, emphasising the importance of building strong patient relationships over other consultation aspects. CONCLUSIONS: This research provides initial insights for GPs in Aboriginal health, comparing experienced GPs with more than 10years experience to novices. However, further research involving Aboriginal patients is needed to validate GP strategies and understand their significance from the patients' perspective.

Cough in Children and Adults: Diagnosis, Assessment and Management (CICADA). Summary of an updated position statement on chronic cough in Australia.

INTRODUCTION: Cough is the most common symptom leading to medical consultation. Chronic cough results in significant health care costs, impairs quality of life, and may indicate the presence of a serious underlying condition. Here, we present a summary of an updated position statement on cough management in the clinical consultation. MAIN RECOMMENDATIONS: Assessment of children and adults requires a focused history of chronic cough to identify any red flag cough pointers that may indicate an underlying disease. Further assessment with examination should include a chest x-ray and spirometry (when age > 6 years). Separate paediatric and adult diagnostic management algorithms should be followed. Management of the underlying condition(s) should follow specific disease guidelines, as well as address adverse environmental exposures and patient/carer concerns. First Nations adults and children should be considered a high risk group. The full statement from the Thoracic Society of Australia and New Zealand and Lung Foundation Australia for managing chronic cough is available at https://lungfoundation.com.au/resources/cicada-full-position-statement. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: Algorithms for assessment and diagnosis of adult and paediatric chronic cough are recommended. High quality evidence supports the use of child-specific chronic cough management algorithms to improve clinical outcomes, but none exist in adults. Red flags that indicate serious underlying conditions requiring investigation or referral should be identified. Early and effective treatment of chronic wet/productive cough in children is critical. Culturally specific strategies for facilitating the management of chronic cough in First Nations populations should be adopted. If the chronic cough does not resolve or is unexplained, the patient should be referred to a respiratory specialist or cough clinic.

Pathogenesis of Rift Valley Fever Virus in a BALB/c Mouse Model Is Affected by Virus Culture Conditions and Sex of the Animals.

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease in livestock and humans. Whilst initially restricted to the African continent, recent spread to the Arabian Peninsula has highlighted the likelihood of entry into new regions. Due to the absence of a regulatory-approved human vaccine, work is ongoing to develop and assess countermeasures. As such, small animal models play a pivotal role in providing information on disease pathogenesis and elucidating which intervention strategies confer protection. To develop and establish the BALB/c mouse model, we challenged mice with RVFV grown from two separate cell lines: one derived from mosquitoes (C6/36) and the other mammalian derived (Vero E6). Following infection, we assessed the clinical course of disease progression at days 1 and 3 post-challenge and evaluated viral tropism and immune analytes. The results demonstrated that RVFV infection was affected by the cell line used to propagate the challenge virus, with those grown in insect cells resulting in a more rapid disease progression. The lowest dose that caused uniform severe disease remained the same across both virus preparations. In addition, to demonstrate reproducibility, the lowest dose was used for a subsequent infection study using male and female animals. The results further demonstrated that male mice succumbed to infection more rapidly than their female counterparts. Our results establish an RVFV mouse model and key parameters that affect the course of disease progression in BALB/c mice.

NF-κB fingerprinting reveals heterogeneous NF-κB composition in diffuse large B-cell lymphoma.

Introduction: Improving treatments for Diffuse Large B-Cell Lymphoma (DLBCL) is challenged by the vast heterogeneity of the disease. Nuclear factor-κB (NF-κB) is frequently aberrantly activated in DLBCL. Transcriptionally active NF-κB is a dimer containing either RelA, RelB or cRel, but the variability in the composition of NF-κB between and within DLBCL cell populations is not known. Results: Here we describe a new flow cytometry-based analysis technique termed "NF-κB fingerprinting" and demonstrate its applicability to DLBCL cell lines, DLBCL core-needle biopsy samples, and healthy donor blood samples. We find each of these cell populations has a unique NF-κB fingerprint and that widely used cell-of-origin classifications are inadequate to capture NF-κB heterogeneity in DLBCL. Computational modeling predicts that RelA is a key determinant of response to microenvironmental stimuli, and we experimentally identify substantial variability in RelA between and within ABC-DLBCL cell lines. We find that when we incorporate NF-κB fingerprints and mutational information into computational models we can predict how heterogeneous DLBCL cell populations respond to microenvironmental stimuli, and we validate these predictions experimentally. Discussion: Our results show that the composition of NF-κB is highly heterogeneous in DLBCL and predictive of how DLBCL cells will respond to microenvironmental stimuli. We find that commonly occurring mutations in the NF-κB signaling pathway reduce DLBCL's response to microenvironmental stimuli. NF-κB fingerprinting is a widely applicable analysis technique to quantify NF-κB heterogeneity in B cell malignancies that reveals functionally significant differences in NF-κB composition within and between cell populations.

A Phase 3b Study for Management of Ocular Side Effects in Patients with Epidermal Growth Factor Receptor-Amplified Glioblastoma Receiving Depatuxizumab Mafodotin.

INTRODUCTION: The Understanding New Interventions with GBM ThErapy (UNITE) study was designed to assess the effect of prophylaxis for ocular side effects (OSEs) in patients with glioblastoma receiving the antibody-drug conjugate (ADC) depatuxizumab mafodotin. UNITE (NCT03419403) was a phase 3b, open-label, randomized, exploratory study performed at 18 research sites in 5 countries. METHODS: The study enrolled adult patients with epidermal growth factor receptor-amplified, histologically confirmed, newly diagnosed supratentorial glioblastoma or grade IV gliosarcoma, and a Karnofsky Performance Status ≥70, receiving depatuxizumab mafodotin. All patients were administered depatuxizumab mafodotin during concurrent radiotherapy and temozolomide and with adjuvant temozolomide. Ninety patients were to be randomized (1:1:1) to OSE prophylactic treatments with each depatuxizumab mafodotin infusion: (a) standard steroid eye drops, (b) standard steroid eye drops plus vasoconstrictor eye drops and cold compress, or (c) enhanced steroids plus vasoconstrictor eye drops and cold compress. A Corneal Epitheliopathy Adverse Event (CEAE) scale was devised to capture symptoms, grade OSEs (scale of 0-5), and inform ADC dose modifications. The primary endpoint was the frequency of a required change in OSE management due to inadequate control of OSEs, defined as decline from baseline in visual acuity (using logarithm of the minimum angle of resolution [LogMAR] scale) or a Grade ≥3 CEAE event, in the worst eye in the first 8 weeks of treatment; unless otherwise specified, the treatment period refers to both the chemoradiation and adjuvant phases. RESULTS: The UNITE study was stopped early after interim analysis of separate phase III trial showed no difference in survival from depatuxizumab mafodotin. Forty patients were randomized (38 received depatuxizumab mafodotin). Overall, 23 patients experienced inadequate control of OSEs that required change in OSE management within 8 weeks of treatment, with 21 (70.0%) experiencing ≥+0.3 change on LogMAR scale in baseline-adjusted visual acuity and 12 reporting a grade ≥3 CEAE. There were no definitive differences among prophylactic treatments. CONCLUSIONS: The premature cessation of the study precludes definitive conclusions regarding the OSE prophylaxis strategies. No new clinically significant safety findings were noted. Despite these limitations, this study highlights the need for novel assessment tools to better understand and mitigate OSEs associated with ADCs.

Thoracic Society of Australia and New Zealand (TSANZ) position statement on chronic suppurative lung disease and bronchiectasis in children, adolescents and adults in Australia and New Zealand.

This position statement, updated from the 2015 guidelines for managing Australian and New Zealand children/adolescents and adults with chronic suppurative lung disease (CSLD) and bronchiectasis, resulted from systematic literature searches by a multi-disciplinary team that included consumers. The main statements are: Diagnose CSLD and bronchiectasis early; this requires awareness of bronchiectasis symptoms and its co-existence with other respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease). Confirm bronchiectasis with a chest computed-tomography scan, using age-appropriate protocols and criteria in children. Undertake a baseline panel of investigations. Assess baseline severity, and health impact, and develop individualized management plans that include a multi-disciplinary approach and coordinated care between healthcare providers. Employ intensive treatment to improve symptom control, reduce exacerbation frequency, preserve lung function, optimize quality-of-life and enhance survival. In children, treatment also aims to optimize lung growth and, when possible, reverse bronchiectasis. Individualize airway clearance techniques (ACTs) taught by respiratory physiotherapists, encourage regular exercise, optimize nutrition, avoid air pollutants and administer vaccines following national schedules. Treat exacerbations with 14-day antibiotic courses based upon lower airway culture results, local antibiotic susceptibility patterns, clinical severity and patient tolerance. Patients with severe exacerbations and/or not responding to outpatient therapy are hospitalized for further treatments, including intravenous antibiotics and intensive ACTs. Eradicate Pseudomonas aeruginosa when newly detected in lower airway cultures. Individualize therapy for long-term antibiotics, inhaled corticosteroids, bronchodilators and mucoactive agents. Ensure ongoing care with 6-monthly monitoring for complications and co-morbidities. Undertake optimal care of under-served peoples, and despite its challenges, delivering best-practice treatment remains the overriding aim.

Adenoviral vectored vaccination protects against Crimean-Congo Haemorrhagic Fever disease in a lethal challenge model.

BACKGROUND: The tick-borne bunyavirus, Crimean-Congo Haemorrhagic Fever virus (CCHFV), can cause severe febrile illness in humans and has a wide geographic range that continues to expand due to tick migration. Currently, there are no licensed vaccines against CCHFV for widespread usage. METHODS: In this study, we describe the preclinical assessment of a chimpanzee adenoviral vectored vaccine (ChAdOx2 CCHF) which encodes the glycoprotein precursor (GPC) from CCHFV. FINDINGS: We demonstrate here that vaccination with ChAdOx2 CCHF induces both a humoral and cellular immune response in mice and 100% protection in a lethal CCHF challenge model. Delivery of the adenoviral vaccine in a heterologous vaccine regimen with a Modified Vaccinia Ankara vaccine (MVA CCHF) induces the highest levels of CCHFV-specific cell-mediated and antibody responses in mice. Histopathological examination and viral load analysis of the tissues of ChAdOx2 CCHF immunised mice reveals an absence of both microscopic changes and viral antigen associated with CCHF infection, further demonstrating protection against disease. INTERPRETATION: There is the continued need for an effective vaccine against CCHFV to protect humans from lethal haemorrhagic disease. Our findings support further development of the ChAd platform expressing the CCHFV GPC to seek an effective vaccine against CCHFV. FUNDING: This research was supported by funding from the Biotechnology and Biological Sciences Research Council (UKRI-BBSRC) [BB/R019991/1 and BB/T008784/1].

Investigating the effect of ribavirin treatment on genetic mutations in Crimean-Congo haemorrhagic fever virus (CCHFV) through next-generation sequencing.

Crimean-Congo haemorrhagic fever (CCHF) is the most widespread tick-borne viral haemorrhagic fever affecting humans, and yet a licensed drug against the virus (CCHFV) is still not available. While several studies have suggested the efficacy of ribavirin against CCHFV, current literature remains inconclusive. In this study, we have utilised next-generation sequencing to investigate the mutagenic effect of ribavirin on the CCHFV genome during clinical disease. Samples collected from CCHF patients receiving ribavirin treatment or supportive care only at Sivas Cumhuriyet University Hospital, Turkey, were analysed. By comparing the frequency of mutations in each group, we found little evidence of an overall mutagenic effect. This suggests that ribavirin, administered at the acute stages of CCHFV infection (at the World Health Organization-recommended dose) is unable to induce lethal mutagenesis that would cause an extinction event in the CCHFV population and reduce viremia.

Development of humanised antibodies for Crimean-Congo Haemorrhagic fever virus: Comparison of hybridoma-based versus phage library techniques.

Humanised antibodies targeting Crimean-Congo Haemorrhagic virus (CCHFV) are needed for the development and standardisation of serological assays. These assays are needed to address a shortfall in available tests that meet regulatory diagnostic standards and to aid surveillance activities to extend knowledge on the distribution of CCHFV. To generate a humanised monoclonal antibody against CCHFV, we have compared two methods: the traditional mouse hybridoma approach with subsequent sequencing and humanisation of antibodies versus a non-animal alternative using a human combinatorial antibody library (HuCAL). Our results demonstrated that the mouse hybridoma followed by humanisation protocol gave higher affinity antibodies. Whilst not yet able to demonstrate the generation of equivalent humanised antibodies without the use of animals, sequencing data enables the subsequent production of recombinant antibodies, thus providing a reduction in future animal usage for this application. Ultimately, our report provides information on development of a humanised standardised control, which can form an important positive control component of serological assays against CCHFV.

Multi-omics insights into host-viral response and pathogenesis in Crimean-Congo hemorrhagic fever viruses for novel therapeutic target.

The pathogenesis and host-viral interactions of the Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) are convoluted and not well evaluated. Application of the multi-omics system biology approaches, including biological network analysis in elucidating the complex host-viral response, interrogates the viral pathogenesis. The present study aimed to fingerprint the system-level alterations during acute CCHFV-infection and the cellular immune responses during productive CCHFV-replication in vitro. We used system-wide network-based system biology analysis of peripheral blood mononuclear cells (PBMCs) from a longitudinal cohort of CCHF patients during the acute phase of infection and after one year of recovery (convalescent phase) followed by untargeted quantitative proteomics analysis of the most permissive CCHFV-infected Huh7 and SW13 cells. In the RNAseq analysis of the PBMCs, comparing the acute and convalescent-phase, we observed system-level host's metabolic reprogramming towards central carbon and energy metabolism (CCEM) with distinct upregulation of oxidative phosphorylation (OXPHOS) during CCHFV-infection. Upon application of network-based system biology methods, negative coordination of the biological signaling systems like FOXO/Notch axis and Akt/mTOR/HIF-1 signaling with metabolic pathways during CCHFV-infection were observed. The temporal quantitative proteomics in Huh7 showed a dynamic change in the CCEM over time and concordant with the cross-sectional proteomics in SW13 cells. By blocking the two key CCEM pathways, glycolysis and glutaminolysis, viral replication was inhibited in vitro. Activation of key interferon stimulating genes during infection suggested the role of type I and II interferon-mediated antiviral mechanisms both at the system level and during progressive replication.

Crimean-Congo hemorrhagic fever (CCHF) is an emerging disease that is increasingly spreading to new populations. The condition is now endemic in almost 30 countries in sub-Saharan Africa, South-Eastern Europe, the Middle East and Central Asia. CCHF is caused by a tick-borne virus and can cause uncontrolled bleeding. It has a mortality rate of up to 40%, and there are currently no vaccines or effective treatments available. All viruses depend entirely on their hosts for reproduction, and they achieve this through hijacking the molecular machinery of the cells they infect. However, little is known about how the CCHF virus does this and how the cells respond. To understand more about the relationship between the cell's metabolism and viral replication, Neogi, Elaldi et al. studied immune cells taken from patients during an infection and one year later. The gene activity of the cells showed that the virus prefers to hijack processes known as central carbon and energy metabolism. These are the main regulator of the cellular energy supply and the production of essential chemicals. By using cancer drugs to block these key pathways, Neogi, Elaldi et al. could reduce the viral reproduction in laboratory cells. These findings provide a clearer understanding of how the CCHF virus replicates inside human cells. By interfering with these processes, researchers could develop new antiviral strategies to treat the disease. One of the cancer drugs tested in cells, 2-DG, has been approved for emergency use against COVID-19 in some countries. Neogi, Elaldi et al. are now studying this further in animals with the hope of reaching clinical trials in the future.

Elucidation of Focal Adhesion Kinase as a Modulator of Migration and Invasion and as a Potential Therapeutic Target in Chronic Lymphocytic Leukemia.

The retention and re-migration of Chronic Lymphocytic Leukemia cells into cytoprotective and proliferative lymphoid niches is thought to contribute to the development of resistance, leading to subsequent disease relapse. The aim of this study was to elucidate the molecular processes that govern CLL cell migration to elicit a more complete inhibition of tumor cell migration. We compared the phenotypic and transcriptional changes induced in CLL cells using two distinct models designed to recapitulate the peripheral circulation, CLL cell migration across an endothelial barrier, and the lymph node interaction between CLL cells and activated T cells. Initially, CLL cells were co-cultured with CD40L-expressing fibroblasts and exhibited an activated B-cell phenotype, and their transcriptional signatures demonstrated the upregulation of pro-survival and anti-apoptotic genes and overrepresentation of the NF-κB signaling pathway. Using our dynamic circulating model, we were able to study the transcriptomics and miRNomics associated with CLL migration. More than 3000 genes were altered when CLL cells underwent transendothelial migration, with an overrepresentation of adhesion and cell migration gene sets. From this analysis, an upregulation of the FAK signaling pathway was observed. Importantly, PTK2 (FAK) gene expression was significantly upregulated in migrating CLL cells (PTK2 Fold-change = 4.9). Here we demonstrate that TLR9 agonism increased levels of p-FAK (p ≤ 0.05), which could be prevented by pharmacological inhibition of FAK with defactinib (p ≤ 0.01). Furthermore, a reduction in CLL cell migration and invasion was observed when FAK was inhibited (p ≤ 0.0001), supporting a role for FAK in both CLL migration and tissue invasion. When taken together, our data highlights the potential for combining FAK inhibition with current targeted therapies as a more effective treatment regime for CLL.

Targeting the Non-Canonical NF-κB Pathway in Chronic Lymphocytic Leukemia and Multiple Myeloma.

In this study, we evaluated an NF-κB inducing kinase (NIK) inhibitor, CW15337, in primary chronic lymphocytic leukemia (CLL) cells, CLL and multiple myeloma (MM) cell lines and normal B- and T-lymphocytes. Basal NF-κB subunit activity was characterized using an enzyme linked immunosorbent assay (ELISA), and the effects of NIK inhibition were then assessed in terms of cytotoxicity and the expression of nuclear NF-κB subunits following monoculture and co-culture with CD40L-expressing fibroblasts, as a model of the lymphoid niche. CW15337 induced a dose-dependent increase in apoptosis, and nuclear expression of the non-canonical NF-κB subunit, p52, was correlated with sensitivity to CW15337 (p = 0.01; r2 = 0.39). Co-culture on CD40L-expressing cells induced both canonical and non-canonical subunit expression in nuclear extracts, which promoted in vitro resistance against fludarabine and ABT-199 (venetoclax) but not CW15337. Furthermore, the combination of CW15337 with fludarabine or ABT-199 showed cytotoxic synergy. Mechanistically, CW15337 caused the selective inhibition of non-canonical NF-κB subunits and the transcriptional repression of BCL2L1, BCL2A1 and MCL1 gene transcription. Taken together, these data suggest that the NIK inhibitor, CW15337, exerts its effects via suppression of the non-canonical NF-κB signaling pathway, which reverses BCL2 family-mediated resistance in the context of CD40L stimulation.

The association of anxiety and stress-related disorders with C-reactive protein (CRP) within UK Biobank.

Anxiety and stress-related disorders are both common and disabling psychiatric conditions. There are a number of hypotheses suggesting the underlying pathophysiology of these disorders, however, the exact mechanism is unknown. Inflammation has previously been linked with depression and has more recently been suggested as a possible link to anxiety aetiology. The objectives of this study are to assess the relationship between different anxiety/stress-related disorders and inflammation (measured by C-reactive protein) using the UK Biobank, and also determine whether any relationship between anxiety/stress disorders and inflammation is explained by depressive symptoms and other social and health-related factors. We utilised the UK Biobank for the sample of this study. Our sample included 353,136 participants of which 12,759 (3.61%) had a history of an anxiety (phobic, obsessive-compulsive, or other anxiety disorder including generalised anxiety and panic disorders) or stress-related disorder (including acute stress reaction, post-traumatic stress disorder and adjustment disorders). Four logistic regression models were calculated in which we tested the association between anxiety/stress disorders and C-reactive protein (CRP) >3 â€‹mg/L, adjusting for covariates (including age, sex, ethnicity, education level, socioeconomic deprivation, depressive symptoms, body mass index (BMI) and multimorbidity). An association was observed between other anxiety disorders (including panic and generalised anxiety disorders) and CRP (OR: 1.164 [95% CI: 1.096-1.236]). This was attenuated in models after the addition of BMI, multimorbidity and depressive symptoms. Stress/adjustment disorders followed a similar pattern of results (OR: 1.107 [95% CI: 1.040, 1.178]), with the association attenuated with the addition of BMI and multimorbidity). Phobic anxiety disorders (OR: 1.059 [95% CI: 0.896, 1.251]) and obsessive-compulsive disorders (OR: 1.299 [95% CI: 0.973, 1.733]) both showed no statistically significant results in any of the models. Our results support the hypothesis that some anxiety and stress-related disorders may be associated with high levels of inflammatory markers, as measured by CRP. Further studies are required to untangle the potential causal relationships involved.

Reef Cover, a coral reef classification for global habitat mapping from remote sensing.

Coral reef management and conservation stand to benefit from improved high-resolution global mapping. Yet classifications underpinning large-scale reef mapping to date are typically poorly defined, not shared or region-specific, limiting end-users' ability to interpret outputs. Here we present Reef Cover, a coral reef geomorphic zone classification, developed to support both producers and end-users of global-scale coral reef habitat maps, in a transparent and version-based framework. Scalable classes were created by focusing on attributes that can be observed remotely, but whose membership rules also reflect deep knowledge of reef form and functioning. Bridging the divide between earth observation data and geo-ecological knowledge of reefs, Reef Cover maximises the trade-off between applicability at global scales, and relevance and accuracy at local scales. Two case studies demonstrate application of the Reef Cover classification scheme and its scientific and conservation benefits: 1) detailed mapping of the Cairns Management Region of the Great Barrier Reef to support management and 2) mapping of the Caroline and Mariana Island chains in the Pacific for conservation purposes.