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Abstract Background Leveraging the Accelerating Medicines Partnership (AMP) Lupus Nephritis (LN) dataset, we evaluated longitudinal patterns, rates, and predictors of response to standard-of-care therapy in patients with lupus nephritis. Methods Patients from US academic medical centers with class III, IV, and/or V LN and a baseline urine protein/creatinine (UPCR) ratio ≥ 1.0 (n = 180) were eligible for this analysis. Complete response (CR) required the following: (1) UPCR 50% reduction in UPCR; (2) normal serum creatinine or, if abnormal, ≤ 125% of baseline; and (3) prednisone dose ≤ 15 mg/day. Results Response rates to the standard of care at week 52 were CR = 22.2%; PR = 21.7%; non-responder (NR) = 41.7%, and not determined (ND) = 14.4%. Only 8/180 (4.4%) patients had a week 12 CR sustained through week 52. Eighteen (10%) patients attained a week 12 PR or CR and sustained their responses through week 52 and 47 (26.1%) patients achieved sustained PR or CR at weeks 26 and 52. Week 52 CR or PR attainment was associated with baseline UPCR > 3 (ORadj = 3.71 [95%CI = 1.34–10.24]; p = 0.012), > 25% decrease in UPCR from baseline to week 12 (ORadj = 2.61 [95%CI = 1.07–6.41]; p = 0.036), lower chronicity index (ORadj = 1.33 per unit decrease [95%CI = 1.10–1.62]; p = 0.003), and positive anti-dsDNA antibody (ORadj = 2.61 [95%CI = 0.93–7.33]; p = 0.069). Conclusions CR and PR rates at week 52 were consistent with the standard-of-care response rates observed in prospective registrational LN trials. Low sustained response rates underscore the need for more efficacious therapies and highlight how critically important it is to understand the molecular pathways associated with response and non-response.

In this study, ultrasound treatment was used to exfoliate commercially available graphite flakes into reduced graphene oxide (rGO) dispersed in ethanol. After centrifugation, solid copper chloride trihydrate was added, resulting in a green liquor containing Cu(II), Cu(I), and rGO. These liquors exhibited good and rapid photocatalytic activity in the degradation of eosin and bromophenol blue dyes (elimination in a few seconds) under visible-light irradiation. UV–visible spectroscopy confirmed the presence of rGO and Cu species. The size and morphology of the rGO sheets were investigated by several methods (SAXS, wide-angle XRD, SEM, and TEM). Negative UV peaks indicated light emission, which was independently verified by fluorescence. Intense plasmon peaks, with absorbances greater than 10, were observed after adding copper chloride salt. These plasmons were eliminated by a high dilution before the described catalytic tests were performed.

BackgroundSocial support is essential to promoting optimal health outcomes for women with breast cancer. However, an estimated 12% of women with breast cancer simultaneously experience intimate partner violence (IPV; physical, psychological, or sexual abuse by an intimate partner). Women who experience IPV during breast cancer may lack traditional social support, and thus seek out alternative sources of support. Online community forums, such as Reddit, can provide accessible social connections within breast cancer–specific communities. However, it is largely unknown how women with breast cancer use Reddit to describe and seek support for experiences of IPV. ObjectiveThis study aims to explore how patients with breast cancer describe toxic relationships with their partners and immediate family members on Reddit. MethodsThis exploratory, cross-sectional, topic-modeling study analyzed textual data from 96 users in the r/breastcancer subreddit in February 2023. The meaning extraction method, inclusive of principal component analysis, was used to identify underlying components. Components were subjected to sentiment analysis and summative content analysis with emergent categorical development to articulate themes. ResultsSeven themes emerged related to toxic relationships: (1) contextualizing storytelling with lymph nodes, (2) toxic behavior and venting emotions, (3) abandonment and abuse following diagnosis, (4) toxic relationships and social-related fears, (5) inner strength and navigating breast cancer over time, (6) assessing social relationships and interactions, and (7) community advice and support. Toxic relationships were commonly characterized by isolation, abandonment, and emotional abuse, which had profound emotional consequences for patients. Reddit facilitated anonymous venting about toxic relationships that helped patients cope with intense feelings and stress. Exchanging advice and support about navigating toxic relationships during breast cancer were core functions of the r/breastcancer community. ConclusionsFindings emphasized the value of Reddit as a source of social support for patients with breast cancer experiencing toxic relationships. Clinicians who understand that many patients with breast cancer experience toxic relationships and considerable psychological sequelae are better prepared to support their patients’ holistic well-being. Further investigation of Reddit as a possible resource for advice, information, and support has the potential to help inform clinical practice and subsequently, patient health outcomes.

Identifying virulence-critical genes from pathogens is often limited by functional redundancy. To rapidly interrogate the contributions of combinations of genes to a biological outcome, we have developed a multiplex, randomized CRISPR interference sequencing (MuRCiS) approach. At its center is a new method for the randomized self-assembly of CRISPR arrays from synthetic oligonucleotide pairs. When paired with PacBio long-read sequencing, MuRCiS allowed for near-comprehensive interrogation of all pairwise combinations of a group of 44 Legionella pneumophila virulence genes encoding highly conserved transmembrane proteins for their role in pathogenesis. Both amoeba and human macrophages were challenged with L. pneumophila bearing the pooled CRISPR array libraries, leading to the identification of several new virulence-critical combinations of genes. lpg2888 and lpg3000 were particularly fascinating for their apparent redundant functions during L. pneumophila human macrophage infection, while lpg3000 alone was essential for L. pneumophila virulence in the amoeban host Acanthamoeba castellanii. Thus, MuRCiS provides a method for rapid genetic examination of even large groups of redundant genes, setting the stage for application of this technology to a variety of biological contexts and organisms.

Catalysts enriched in Zinc ferrite (ZFO) were synthesized using coprecipitation and hydrothermal methods. Mixtures of crystalline nanoparticles (ZFO and α-Fe2O3, several allotropic varieties of FeO) were characterized by various techniques such as X-ray diffraction (XRD), transmission electron microscopy (TEM, SEM), N2 sorption, UV-visible spectrophotometry (UV-Vis) and X-ray photoelectron spectroscopy (XPS). After detailed characterizations, the catalytic performance of the solids (1 g/L) in the degradation of amoxicillin (AMX) (10 mg/L) as an antibiotic pollutant in water was evaluated. In addition, we used air as the oxygen source and adjusted the pH to 5.0. Consequently, the catalysts obtained via the hydrothermal method HT-ZFO had a high activity (100% of AMX removal in less than 100 min when an LED (75 W) light was used) compared to a similar mixture of oxides with graphene HT-ZFO-GO (a longer time of 150 min) that was necessary for the complete degradation of AMX. Impregnation with an aqueous solution containing 80 mg of GO obtained using Hummer’s method, reduced into RGO by an ultrasound treatment, enhances the initial reaction rate but is associated with a prolonged time for complete AMX removal (10 ppm in water) that we attribute to its spontaneous corrosion.

Abstract Background We have found disruption of expression of major transcriptional regulators of circadian rhythm in the kidneys of several mouse models of lupus nephritis. Here we define the consequence of this disturbance with respect to circadian gene expression and renal homeostatic function in a mouse model of lupus nephritis. Methods Molecular profiling of kidneys from 47 young and 41 nephritic female NZB/W F1 mice was performed at 4 hourly intervals over a 24 h period. Disruption of major circadian transcriptional regulators was confirmed by qPCR. Molecular data was normalized and analyzed for rhythmicity using RAIN analysis. Serum aldosterone and glucose and urine sodium and potassium were measured at 4 hourly intervals in pre-nephritic and nephritic mice and blood pressure was measured every 4 h. Analyses were repeated after induction of complete remission of nephritis using combination cyclophosphamide and costimulatory blockade. Results We show a profound alteration of renal circadian rhythms in mice with lupus nephritis affecting multiple renal pathways. Using Cosinor analysis we identified consequent alterations of renal homeostasis and metabolism as well as blood pressure dipper status. This circadian dysregulation was partially reversed by remission induction therapy. Conclusions Our studies indicate the role of inflammation in causing the circadian disruption and suggest that screening for loss of normal blood pressure dipping should be incorporated into LN management. The data also suggest a potential role for circadian agonists in the treatment of lupus nephritis.

Objectives To report on knowledge translation strategies and outcomes from the implementation of the early detection guidelines for cerebral palsy (CP) in a state-wide tertiary early intervention (EI) service and investigate the impact of social determinants on clinical services.Design Retrospective longitudinal cohort study.Setting The Western Australia tertiary paediatric EI service.Participants EI clinicians, consumers and children using the EI service.Outcome measures Knowledge translation strategies including consumer perspectives, clinician training and Communities of Practice (CoP) guided implementation. We measured changes in referral number and age, delivery of early detection and intervention following the implementation of the guidelines. Exposure to adverse childhood experiences (ACEs), appointment non-attendance (DNA) rates, remoteness and socioeconomic quintiles were used to measure social determinants of health using negative binomial (Incidence Rate Ratios, IRR) and logistic regression (Odds Ratios, ORs).Results Ten consumers participated in Focus Groups, 100 clinicians were trained and 22 clinicians established a monthly CoP. Referrals increased fourfold to 511 children. Corrected gestational age at referral decreased from a median of 16.1 to 5.1 months (p

Renal mononuclear phagocytes are a highly pleiotropic group of immune cells of myeloid origin that play multiple protective and pathogenic roles in tissue homeostasis, inflammation, repair, and fibrosis. Infiltration of kidneys with these cells is a hallmark of lupus nephritis and is associated with more severe disease and with increased risk of progression to end‐stage renal disease. This review presents current knowledge of the diversity of these cells and their involvement in kidney inflammation and resolution and describes how they contribute to the chronic inflammation of lupus nephritis. A better understanding of the subset heterogeneity and diverse functions of mononuclear phagocytes in the lupus nephritis kidney should provide fertile ground for the development of new therapeutic approaches that promote the differentiation and survival of protective subsets while targeting pathogenic cell subsets that cause inflammation and fibrosis.

NADPH oxidase deficiency exacerbates lupus in murine models and patients, but the mechanisms remain unknown. It is hypothesized that NADPH oxidase suppresses autoimmunity by facilitating dead cell clearance via LC3-associated phagocytosis (LAP). The absence of LAP reportedly causes an autoinflammatory syndrome in aged, nonautoimmune mice. Prior work implicated cytochrome b-245, β polypeptide (CYBB), a component of the NADPH oxidase complex, and the RUN and cysteine-rich domain-containing Beclin 1–interacting protein (RUBICON) as requisite for LAP. To test the hypothesis that NADPH oxidase deficiency exacerbates lupus via a defect in LAP, we deleted Rubicon in the B6.Sle1.Yaa and MRL.Faslpr lupus mouse models. Under this hypothesis, RUBICON deficiency should phenocopy NADPH oxidase deficiency, as both work in the same pathway. However, we observed the opposite — RUBICON deficiency resulted in reduced mortality, renal disease, and autoantibody titers to RNA-associated autoantigens. Given that our data contradict the published role for LAP in autoimmunity, we assessed whether CYBB and RUBICON are requisite for LAP. We found that LAP is not dependent on either of these 2 pathways. To our knowledge, our data reveal RUBICON as a novel regulator of SLE, possibly by a B cell–intrinsic mechanism, but do not support a role for LAP in lupus.

TNF inhibitors are widely used to treat inflammatory diseases; however, 30%–50% of treated patients develop new autoantibodies, and 0.5%–1% develop secondary autoimmune diseases, including lupus. TNF is required for formation of germinal centers (GCs), the site where high-affinity autoantibodies are often made. We found that TNF deficiency in Sle1 mice induced TH17 T cells and enhanced the production of germline encoded, T-dependent IgG anti-cardiolipin antibodies but did not induce GC formation or precipitate clinical disease. We then asked whether a second hit could restore GC formation or induce pathogenic autoimmunity in TNF-deficient mice. By using a range of immune stimuli, we found that somatically mutated autoantibodies and clinical disease can arise in the setting of TNF deficiency via extrafollicular pathways or via atypical GC-like pathways. This breach of tolerance may be due to defects in regulatory signals that modulate the negative selection of pathogenic autoreactive B cells.

Abstract Background The aim of this study is to contribute to the knowledge base on the long-term outcomes of evidence-based medical interventions used to improve gross motor function in children and adolescents with Cerebral Palsy. Method Prospective cohort study of children with Cerebral Palsy in the birth years 2000–2009 attending a tertiary level service for children with Cerebral Palsy who’s first recorded Gross Motor Function Classification System level was II. Results A total of 40 children were eligible for the study, of whom 28 (72.7%) enrolled. The Botulinum toxin A treatment for this cohort, (median and interquartile ranges) were: total number of lower limb Botulinum toxin A injections 11 (6.7, 5.5); total dose of Botulinum Toxin A per lower limb treatment 6.95 u/kg (4.5, 11); and dose of Botulinum Toxin u/kg/muscle 2.95 (2.2, 4). For all 28 subjects there was a median of 15 (8.5 to 22) Gross Motor Function Classification System level recordings: six of the 28 children (21.4%) improved from level II to level I, the remaining 22 children remained stable at level II (78.6%). In this highly treated population, the average 66 item Gross Motor Function Measure score for the 22 children in level II was 72.55, which is consistent with the mean of 68.5 reported in the original Ontario cohort. Conclusion This cohort study has confirmed that children with Cerebral Palsy, Gross Motor Function level II treated at a young age with repeated doses of Botulinum Toxin A within an integrated comprehensive service, maintain or improve their functional motor level at a later age.

Objectives In lupus nephritis the pathological diagnosis from tissue retrieved during kidney biopsy drives treatment and management. Despite recent approval of new drugs, complete remission rates remain well under aspirational levels, necessitating identification of new therapeutic targets by greater dissection of the pathways to tissue inflammation and injury. This study assessed the safety of kidney biopsies in patients with SLE enrolled in the Accelerating Medicines Partnership, a consortium formed to molecularly deconstruct nephritis.Methods 475 patients with SLE across 15 clinical sites in the USA consented to obtain tissue for research purposes during a clinically indicated kidney biopsy. Adverse events (AEs) were documented for 30 days following the procedure and were determined to be related or unrelated by all site investigators. Serious AEs were defined according to the National Institutes of Health reporting guidelines.Results 34 patients (7.2%) experienced a procedure-related AE: 30 with haematoma, 2 with jets, 1 with pain and 1 with an arteriovenous fistula. Eighteen (3.8%) experienced a serious AE requiring hospitalisation; four patients (0.8%) required a blood transfusion related to the kidney biopsy. At one site where the number of cores retrieved during the biopsy was recorded, the mean was 3.4 for those who experienced a related AE (n=9) and 3.07 for those who did not experience any AE (n=140). All related AEs resolved.Conclusions Procurement of research tissue should be considered feasible, accompanied by a complication risk likely no greater than that incurred for standard clinical purposes. In the quest for targeted treatments personalised based on molecular findings, enhanced diagnostics beyond histology will likely be required.

Preserving biodiversity and its many components is a priority of conservation science and how to efficiently allocate resources to preserve healthy populations of as many species, habitats, and ecosystems as possible. We used the U.S. Geological Survey (USGS) Gap Analysis Project (GAP) species models released in 2018, which identify predicted habitats for terrestrial vertebrates in the conterminous United States, to illustrate hotspots of biodiversity for the major taxonomic groups. This collection represents the first complete compilation of terrestrial vertebrate species models for the conterminous United States (U.S. Geological Survey (USGS), 2018a). We used the species models but not the available subspecies models; this resulted in the inclusion of 282 amphibian models, 621 bird models, 365 mammal models, and 322 reptiles in our analysis. We also used population trend information and made spatial queries to characterize species in three dimensions: geographic range (small or large), habitat breadth (narrow or wide), and population trend (decreasing vs stable or increasing). This characterization allowed us to divide the species into eight groups (A-H) with similar characteristics. Group A species (large geographic range, wide habitat breadth, and stable or increasing population trend) are species that are common now with no indication of becoming rare. Species B-H have theoretical or known characteristics that could lead them to become rare with the H species exhibiting small geographic range, narrow habitat breadth, and decreasing population trend. Finally, we evaluated the prevalence of mapped habitat on protected lands for each species, exploring the patterns of representation in the rare species groups by ecoregion. The species we identified with population and habitat use characteristics that potentially predispose them to being or becoming rare represented a large percentage of each taxon. Potentially rare species were widely distributed among ecoregions. Of the 20 ecoregions in the country, 14 have a greater number of rare species than the national average for at least one taxon. Protection of the habitat for the majority of these rare species is below that recommended (17% of available habitat) by the Convention on Biological Diversity (CBD). The Everglades ecoregion was the only ecoregion that protected more than half of its rare or potentially rare species.

Abstract Background Some interventions are developed from practice, and implemented before evidence of effect is determined, or the intervention is fully specified. An example is Namaste Care, a multi-component intervention for people with advanced dementia, delivered in care home, community, hospital and hospice settings. This paper describes the development of an intervention description, guide and training package to support implementation of Namaste Care within the context of a feasibility trial. This allows fidelity to be determined within the trial, and for intervention users to understand how similar their implementation is to that which was studied. Methods A four-stage approach: a) Collating existing intervention materials and drawing from programme theory developed from a realist review to draft an intervention description. b) Exploring readability, comprehensibility and utility with staff who had not experienced Namaste Care. c) Using modified nominal group techniques with those with Namaste Care experience to refine and prioritise the intervention implementation materials. d) Final refinement with a patient and public involvement panel. Results Eighteen nursing care home staff, one carer, one volunteer and five members of our public involvement panel were involved across the study steps. A 16-page A4 booklet was designed, with flow charts, graphics and colour coded information to ease navigation through the document. This was supplemented by infographics, and a training package. The guide describes the boundaries of the intervention and how to implement it, whilst retaining the flexible spirit of the Namaste Care intervention. Conclusions There is little attention paid to how best to specify complex interventions that have already been organically implemented in practice. This four-stage process may have utility for context specific adaptation or description of existing, but untested, interventions. A robust, agreed, intervention and implementation description should enable a high-quality future trial. If an effect is determined, flexible practice implementation should be enabled through having a clear, evidence-based guide.

Introduction The current diagnostic pathways for cognitive impairment rarely identify babies at risk before 2 years of age. Very early detection and timely targeted intervention has potential to improve outcomes for these children and support them to reach their full life potential. Early Moves aims to identify early biomarkers, including general movements (GMs), for babies at risk of cognitive impairment, allowing early intervention within critical developmental windows to enable these children to have the best possible start to life.Method and analysis Early Moves is a double-masked prospective cohort study that will recruit 3000 term and preterm babies from a secondary care setting. Early Moves will determine the diagnostic value of abnormal GMs (at writhing and fidgety age) for mild, moderate and severe cognitive delay at 2 years measured by the Bayley-4. Parents will use the Baby Moves smartphone application to video their babies’ GMs. Trained GMs assessors will be masked to any risk factors and assessors of the primary outcome will be masked to the GMs result. Automated scoring of GMs will be developed through applying machine-based learning to the data and the predictive value for an abnormal GM will be investigated. Screening algorithms for identification of children at risk of cognitive impairment, using the GM assessment (GMA), and routinely collected social and environmental profile data will be developed to allow more accurate prediction of cognitive outcome at 2 years. A cost evaluation for GMA implementation in preparation for national implementation will be undertaken including exploring the relationship between cognitive status and healthcare utilisation, medical costs, health-related quality of life and caregiver burden.Ethics and dissemination Ethics approval has been granted by the Medical Research Ethics Committee of Joondalup Health Services and the Health Service Human Research Ethics Committee (1902) of Curtin University (HRE2019-0739).Trial registration number ACTRN12619001422112.

Background: People with advanced dementia who live and die in nursing homes experience variable quality of life, care and dying. There is a need to identify appropriate, cost-effective interventions that facilitate high-quality end-of-life care provision. Objectives: To establish the feasibility and acceptability to staff and family of conducting a cluster randomised controlled trial of the Namaste Care intervention for people with advanced dementia in nursing homes. Design: The study had three phases: (1) realist review and (2) intervention refinement to inform the design of (3) a feasibility cluster randomised controlled trial with a process evaluation and economic analysis. Clusters (nursing homes) were randomised in a 3 : 1 ratio to intervention or control (usual care). The nature of the intervention meant that blinding was not possible. Setting: Nursing homes in England providing care for people with dementia. Participants: Residents with advanced dementia (assessed as having a Functional Assessment Staging Test score of 6 or 7), their informal carers and nursing home staff. Intervention: Namaste Care is a complex group intervention that provides structured personalised care in a dedicated space, focusing on enhancements to the physical environment, comfort management and sensory engagement. Main outcome measures: The two contender primary outcome measures were Comfort Assessment in Dying – End of Life Care in Dementia for quality of dying (dementia) and Quality of Life in Late Stage Dementia for quality of life. The secondary outcomes were as follows: person with dementia, sleep/activity (actigraphy), neuropsychiatric symptoms, agitation and pain; informal carers, satisfaction with care at the end of life; staff members, person-centred care assessment, satisfaction with care at the end of life and readiness for change; and other data – health economic outcomes, medication/service use and intervention activity. Results: Phase 1 (realist review; 86 papers) identified that a key intervention component was the activities enabling the development of moments of connection. In phase 2, refinement of the intervention enabled the production of a user-friendly 16-page A4 booklet. In phase 3, eight nursing homes were recruited. Two homes withdrew before the intervention commenced; four intervention and two control homes completed the study. Residents with advanced dementia (n = 32) were recruited in intervention (n = 18) and control (n = 14) homes. Informal carers (total, n = 12: intervention, n = 5; control, n = 7) and 97 staff from eight sites (intervention, n = 75; control, n = 22) were recruited over a 6-month period. Recruitment is feasible. Completion rates of the primary outcome questionnaires were high at baseline (100%) and at 4 weeks (96.8%). The Quality of Life in Late Stage Dementia was more responsive to change over 24 weeks. Even where economic data were missing, these could be collected in a full trial. The intervention was acceptable; the dose varied depending on the staffing and physical environment of each care home. Staff and informal carers reported changes for the person with dementia in two ways: increased social engagement and greater calm. No adverse events related to the intervention were reported. Conclusions: A subsequent definitive trial is feasible if there are amendments to the recruitment process, outcome measure choice and intervention specification. Future work: In a full trial, consideration is needed of the appropriate outcome measure that is sensitive to different participant responses, and of clear implementation principles for this person-centred intervention in a nursing home context. Trial registration: Current Controlled Trials ISRCTN14948133. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 6. See the NIHR Journals Library website for further project information.

To date, the treatment of immune-mediated kidney diseases has only marginally benefited from highly specific biological drugs that have demonstrated remarkable effects in many other diseases. What accounts for this disparity? In April 2016, the International Society of Nephrology held a Nexus meeting on Translational Immunology in Nephrology in Berlin, Germany, to identify and discuss hurdles that block the translational flow of target identification, and preclinical and clinical target validation in the domain of immune-mediated kidney disease. A broad panel of experts including basic scientists, translational researchers, clinical trialists, pharmaceutical industry drug developers, and representatives of the American and European regulatory authorities made recommendations on how to overcome such hurdles at all levels of the translational research process. The results of these discussions are presented here, which may serve as a roadmap for how to optimize the process of developing more innovative and effective drugs for patients with immune-mediated kidney diseases.

Abstract The goal of this study was to determine how B-cell-activating factor of the TNF family (BAFF) availability influences selection of the autoreactive B-cell repertoire in NZB/W and NZW/BXSB lupus-prone mice bearing the site-directed heavy-chain transgene 3H9 that encodes for anti-dsDNA and anti-cardiolipin (CL) autoantibodies. We used a bone marrow chimera system in which autoreactive 3H9 transgenic B cells were allowed to mature in competition with wild-type cells and could be identified by green fluorescent protein. The light-chain repertoire associated with the 3H9 heavy chain in naive and antigen-activated B-cell subsets was assessed using single-cell polymerase chain reaction. We found that deletion of autoreactive transgenic B cells occurred in the bone marrow of both strains regardless of BAFF availability, and there were only modest and physiologically non-relevant effects on the naive B-cell repertoire. BAFF inhibition had different effects on selection of the germinal center repertoire in the two strains. In the NZW/BXSB strain, BAFF inhibition phenocopied the loss of one TLR7 allele in that it influenced the selection of 3H9-encoded autoreactive B cells in the germinal center but did not prevent somatic mutation. In the NZB/W strain, BAFF inhibition did not alter the selection of 3H9-encoded B cells in the germinal center, but it influenced selection of a subset of germinal center cells into the plasma cell compartment. Our data underscore the complexity of regulation of the autoreactive B-cell repertoire by BAFF and may help to explain the heterogeneity of responses observed after BAFF inhibition in humans.

LANDFIRE (LF) National (2001) was the original product suite of the LANDFIRE program, which included Existing Vegetation Cover (EVC), Height (EVH), and Type (EVT). Subsequent refinements after feedback from data users resulted in updated products, referred to as LF 2001, that now served as LANDFIRE’s baseline datasets and are the basis for all subsequent LANDFIRE updates. These updates account for disturbances and vegetation transition changes that may not represent current vegetation conditions. Therefore, in 2016 LANDFIRE initiated the Remap prototype to determine how to undertake a national-scale remap of the LANDFIRE primary vegetation datasets. EVC, EVH, and EVT were produced (circa 2015) via modeling for ecologically variable prototyping areas in the Pacific Northwest (NW) and Grand Canyon (GC). An error analysis within the GC suggested an overall accuracy of 52% (N = 800) for EVT, and a goodness of fit of 51% (N = 38) for percent cover (continuous EVC) and 53% (N = 38) for height (continuous EVH). The prototyping effort included a new 81-class map using the National Vegetation Classification (NVC) within the NW. This paper presents a narrative of the innovative methodologies in image processing and mapping used to create the new LANDFIRE vegetation products.

In the past decade or so there has been a well-documented decline in language take-up among secondary school pupils of Years 10 and 11 in England (14-16-year-olds, also referred to as Key Stage 4 in the national curriculum for England and Wales) and there have been fewer UK-domiciled undergraduates or postgraduates studying for a languages degree (a decrease of 5.7% and 2.3%, respectively in the academic year 2005-06 by comparison with 2002-03 (CILT 2009). However, having tracked trends in language learning for over a decade and in the light of our various research initiatives, at CILT, the National Centre for Languages, we believe that there are reasons for restrained optimism about the future of the UK's national capability in languages.

Abstract Chemokines facilitate the recruitment of inflammatory cells into tissues, contributing to target organ injury in a wide range of inflammatory and autoimmune diseases. Targeting either single chemokines or chemokine receptors alters the progression of disease in animal models of rheumatoid arthritis and lupus with varying degrees of efficacy, but clinical trials in humans have been less successful. Given the redundancy of chemokine-chemokine receptor interactions, targeting of more than one chemokine may be required to inhibit active inflammatory disease. To test the effects of multiple chemokine blockade in inflammation, we generated an adenovirus expressing bovine herpesvirus 1 glycoprotein G (BHV1gG), a viral chemokine antagonist that binds to a wide spectrum of murine and human chemokines, fused to the fragment crystallizable (Fc) portion of murine immunoglobulin (IgG)2a. Administration of the adenovirus significantly inhibited thioglycollate-induced migration of polymorphonuclear leukocytes into the peritoneal cavity of BALB/c mice and reduced both clinical severity and articular damage in K/BxN serum transfer-induced arthritis. However, treatment with BHV1gG-Ig fusion protein did not prevent monocyte infiltration into the peritoneum in the thioglycollate model and did not prevent renal monocyte infiltration or nephritis in lupus-prone NZB/W mice. These observations suggest that the simultaneous inhibition of multiple chemokines by BHV1gG has the potential to interfere with acute inflammatory responses mediated by polymorphonuclear leukocytes, but is less effective in chronic inflammatory disease mediated by macrophages.