Possibilities for Farm Policy in a Trump Era

This essay addresses options for the Trump administration in promoting a modern, sustainable, and inclusive agricultural system. This essay considers what might be achieved while the Trump administration stays committed to its goals, espoused throughout the Trump campaign. The particularly relevant goals affecting the administration’s agricultural policy are shrinking government, decreasing the number of illegal immigrants, and renegotiating free trade

Blood-Brain Barrier Permeability and Long-Term Clinical and Imaging Outcomes in Cerebral Small Vessel Disease

BACKGROUND AND PURPOSE: Increased blood-brain barrier (BBB) permeability occurs in cerebral small vessel disease (SVD). It is not known if BBB changes predate progression of SVD. METHODS: We followed up patients with non-disabling lacunar or cortical stroke and BBB permeability MR imaging following their original stroke. About three years later, we assessed functional outcome (Oxford Handicap Score, OHS, poor outcome defined as 3-6), recurrent neurological events and white matter hyperintensity (WMH) progression on MRI. RESULTS: Amongst 70 patients, mean age 68 (SD±11) years, median time to clinical follow up was 39 months (IQR 30-45), median OHS was 2 (IQR 1-3); poor functional outcome was associated with higher baseline WMH score (p<0.001) and increased basal ganglia BBB permeability (p=0.046). Amongst 48 patients with follow-up MRI, WMH progression at follow-up was associated with baseline WMH (ANCOVA p<0.0001) and age (ANCOVA p=0.032). CONCLUSIONS: Further long term studies to evaluate the role of BBB dysfunction in progression of SVD are required in studies that are large enough to account for key prognostic influences such as baseline WMH and age

Reductions in radiographic progression in early RA over 25-years: changing contribution from RF in 2 multi-centre UK inception cohorts

Objectives: To assess 5-year progression of erosions and Joint Space Narrowing (JSN), and their associations with RF status in two large, multi-centre early-RA cohorts spanning 25-years. Methods: Radiographic joint damage was recorded using the Sharp/van der Heijde (SvdH) method in the Early RA Study (ERAS) 1986-2001, and the Early RA Network (ERAN) 2002-2013. Mixed-effects negative-binomial regression estimated changes in radiographic damage over 5-years, including erosions and JSN separately. Rheumatoid Factor (RF), along with age, sex and baseline markers of disease activity were controlled for. Results: 1,216 patients from ERAS and 446 from ERAN had radiographic data. Compared to ERAS, ERAN patients had a lower mean total SvdH score at baseline (ERAN=6.2 vs. ERAS=10.5, p<0.001), and mean annual rate of change (ERAN=2.5 vs. ERAS=6.9 per year, p<0.001). 74% of ERAS and 27% of ERAN patients progressed ≥5 units. Lower scores at baseline in ERAN were largely driven by reductions in JSN (ERAS=3.9 vs. ERAN=1.2, p<0.001), along with erosions (ERAS=1.9 vs. ERAN=0.8, p<0.001). RF was associated with greater progression in each cohort, but the absolute difference in mean annual rate of change for RF positive patients was substantially higher for ERAS (RF+= 8.6 vs. RF-= 5.1, p<0.001), relative to ERAN (RF+= 2.0 vs. RF-= 1.9, p=0.855). Conclusion: Radiographic progression has significantly reduced between the two cohorts, associated with lower baseline damage and other factors, including changes in early DMARD use. The impact of RF status as a prognostic marker of clinically meaningful change in radiographic progression has markedly diminished in the context of more modern treatment. This article is protected by copyright. All rights reserved

Reductions in radiographic progression in early RA over 25-years: changing contribution from RF in 2 multi-centre UK inception cohorts

Objectives: To assess 5-year progression of erosions and Joint Space Narrowing (JSN), and their associations with RF status in two large, multi-centre early-RA cohorts spanning 25-years. Methods: Radiographic joint damage was recorded using the Sharp/van der Heijde (SvdH) method in the Early RA Study (ERAS) 1986-2001, and the Early RA Network (ERAN) 2002-2013. Mixed-effects negative-binomial regression estimated changes in radiographic damage over 5-years, including erosions and JSN separately. Rheumatoid Factor (RF), along with age, sex and baseline markers of disease activity were controlled for. Results: 1,216 patients from ERAS and 446 from ERAN had radiographic data. Compared to ERAS, ERAN patients had a lower mean total SvdH score at baseline (ERAN=6.2 vs. ERAS=10.5, p<0.001), and mean annual rate of change (ERAN=2.5 vs. ERAS=6.9 per year, p<0.001). 74% of ERAS and 27% of ERAN patients progressed ≥5 units. Lower scores at baseline in ERAN were largely driven by reductions in JSN (ERAS=3.9 vs. ERAN=1.2, p<0.001), along with erosions (ERAS=1.9 vs. ERAN=0.8, p<0.001). RF was associated with greater progression in each cohort, but the absolute difference in mean annual rate of change for RF positive patients was substantially higher for ERAS (RF+= 8.6 vs. RF-= 5.1, p<0.001), relative to ERAN (RF+= 2.0 vs. RF-= 1.9, p=0.855). Conclusion: Radiographic progression has significantly reduced between the two cohorts, associated with lower baseline damage and other factors, including changes in early DMARD use. The impact of RF status as a prognostic marker of clinically meaningful change in radiographic progression has markedly diminished in the context of more modern treatment. This article is protected by copyright. All rights reserved

Beetle (Coleoptera: Scirtidae) Facilitation of Larval Mosquito Growth in Tree Hole Habitats is Linked to Multitrophic Microbial Interactions

Container-breeding mosquitoes, such as Aedes triseriatus, ingest biofilms and filter water column microorganisms directly to obtain the bulk of their nutrition. Scirtid beetles often co-occur with A. triseriatus and may facilitate the production of mosquito adults under low-resource conditions. Using molecular genetic techniques and quantitative assays, we observed changes in the dynamics and composition of bacterial and fungal communities present on leaf detritus and in the water column when scirtid beetles co-occur with A. triseriatus. Data from terminal restriction fragment polymorphism analysis indicated scirtid presence alters the structure of fungal communities in the water column but not leaf-associated fungal communities. Similar changes in leaf and water bacterial communities occurred in response to mosquito presence. In addition, we observed increased processing of leaf detritus, higher leaf-associated enzyme activity, higher bacterial productivity, and higher leaf-associated fungal biomass when scirtid beetles were present. Such shifts suggest beetle feeding facilitates mosquito production indirectly through the microbial community rather than directly through an increase in available fine particulate organic matter

Urban biodiversity : State of the science and future directions

Since the 1990s, recognition of urban biodiversity research has increased steadily. Knowledge of how ecological communities respond to urban pressures can assist in addressing global questions related to biodiversity. To assess the state of this research field in meeting this aim, we conducted a systematic review of the urban biodiversity literature published since 1990. We obtained data from 1209 studies that sampled ecological communities representing 12 taxonomic groups. While advances have been made in the field over the last 30 years, we found that urban biodiversity research has primarily been conducted in single cities within the Palearctic and Nearctic realms, within forest remnants and residential locations, and predominantly surveys plants and birds, with significant gaps in research within the Global South and little integration of multi-species and multi-trophic interactions. Sample sizes remain limited in spatial and temporal scope, but citizen science and remote sensing resources have broadened these efforts. Analytical approaches still rely on taxonomic diversity to describe urban plant and animal communities, with increasing numbers of integrated phylogenetic and trait-based analyses. Despite the implementation of nature-based solutions across the world's cities, only 5% of studies link biodiversity to ecosystem function and services, pointing to substantial gaps in our understanding of such solutions. We advocate for future research that encompasses a greater diversity of taxonomic groups and urban systems, focusing on biodiversity hotspots. Implementing such research would enable researchers to move forward in an equitable and multidisciplinary way to tackle the complex issues facing global urban biodiversity.Peer reviewe

Specialization of an Exonuclease III family enzyme in the repair of 3′ DNA lesions during base excision repair in the human pathogen Neisseria meningitidis

We have previously demonstrated that the two Exonuclease III (Xth) family members present within the obligate human pathogen Neisseria meningitidis, NApe and NExo, are important for survival under conditions of oxidative stress. Of these, only NApe possesses AP endonuclease activity, while the primary function of NExo remained unclear. We now reveal further functional specialization at the level of 3′-PO4 processing for NExo. We demonstrate that the bi-functional meningococcal glycosylases Nth and MutM can perform strand incisions at abasic sites in addition to NApe. However, no such functional redundancy exists for the 3′-phosphatase activity of NExo, and the cytotoxicity of 3′-blocking lesions is reflected in the marked sensitivity of a mutant lacking NExo to oxidative stress, compared to strains deficient in other base excision repair enzymes. A histidine residue within NExo that is responsible for its lack of AP endonuclease activity is also important for its 3′-phosphatase activity, demonstrating an evolutionary trade off in enzyme function at the single amino acid level. This specialization of two Xth enzymes for the 3′-end processing and strand-incision reactions has not previously been observed and provides a new paradigm within the prokaryotic world for separation of these critical functions during base excision repair

One-Step Preservation of Phosphoproteins and Tissue Morphology at Room Temperature for Diagnostic and Research Specimens

BACKGROUND: There is an urgent need to measure phosphorylated cell signaling proteins in cancer tissue for the individualization of molecular targeted kinase inhibitor therapy. However, phosphoproteins fluctuate rapidly following tissue procurement. Snap-freezing preserves phosphoproteins, but is unavailable in most clinics and compromises diagnostic morphology. Formalin fixation preserves tissue histomorphology, but penetrates tissue slowly, and is unsuitable for stabilizing phosphoproteins. We originated and evaluated a novel one-step biomarker and histology preservative (BHP) chemistry that stabilizes signaling protein phosphorylation and retains formalin-like tissue histomorphology with equivalent immunohistochemistry in a single paraffin block. RESULTS: Total protein yield extracted from BHP-fixed, routine paraffin-embedded mouse liver was 100% compared to snap-frozen tissue. The abundance of 14 phosphorylated proteins was found to be stable over extended fixation times in BHP fixed paraffin embedded human colon mucosa. Compared to matched snap-frozen tissue, 8 phosphoproteins were equally preserved in mouse liver, while AMPKβ1 Ser108 was slightly elevated after BHP fixation. More than 25 tissues from mouse, cat and human specimens were evaluated for preservation of histomorphology. Selected tissues were evaluated in a multi-site, independent pathology review. Tissue fixed with BHP showed equivalent preservation of cytoplasmic and membrane cytomorphology, with significantly better nuclear chromatin preservation by BHP compared to formalin. Immunohistochemical staining of 13 non-phosphorylated proteins, including estrogen receptor alpha, progesterone receptor, Ki-67 and Her2, was equal to or stronger in BHP compared to formalin. BHP demonstrated significantly improved immunohistochemical detection of phosphorylated proteins ERK Thr202/Tyr204, GSK3-α/β Ser21/Ser9, p38-MAPK Thr180/Tyr182, eIF4G Ser1108 and Acetyl-CoA Carboxylase Ser79. CONCLUSION: In a single paraffin block BHP preserved the phosphorylation state of several signaling proteins at a level comparable to snap-freezing, while maintaining the full diagnostic immunohistochemical and histomorphologic detail of formalin fixation. This new tissue fixative has the potential to greatly facilitate personalized medicine, biobanking, and phospho-proteomic research

Have Radiographic Progression Rates in Early Rheumatoid Arthritis Changed? : A Systematic Review and Meta-analysis of Long-term Cohorts

This is a pre-copyedited, author-produced version of an article accepted for publication in Rheumatology following peer review. The version of record: Lewis Carpenter, et al, ‘Have radiographic progression rates in early rheumatoid arthritis changed? A systematic review and meta-analysis of long-term cohorts’ Rheumatology, Vol. 55(6): 1053-1065, 1 June 2016, is available online at DOI: https://doi.org/10.1093/rheumatology/kew004.The objectives of this systematic review are to evaluate firstly, all published data on baseline and annual progression rates of radiographic damage from all longitudinal observational cohorts, and secondly, the association of standard clinical and laboratory parameters with long-term radiographic joint damage.MethodsA comprehensive search of the literature from 1975 to 2014, using PubMed, SCOPUS and Cochrane databases, identified a total of 28 studies that investigated long-term radiographic progression, and 41 studies investigating predictors of long-term radiographic progression. This was submitted and approved by PROSPERO in February 2014 (Registration Number: CRD42014007589).ResultsMeta-analysis indicated an overall baseline rate of 2.02%, and a yearly increase of 1.08% of maximum damage. Stratified analysis found that baseline radiographic scores did not differ significantly between cohorts recruiting patient’s pre and post 1990 (2.01% vs. 2.03%; p>0.01), however the annual rate of progression was significantly reduced in the post 1990 cohorts (0.68% vs. 1.50%; p<0.05). High levels of acute phase markers, baseline radiographic damage, anti-CCP and Rheumatoid Factor positivity remain consistently predictive of long-term radiographic joint damage. Conclusions: Critical changes in treatment practices over the last three decades are likely to explain the reduction in the long-term progression of structural joint damage. Acute phase markers and presence of Rheumatoid Factor/anti-CCP are strongly associated with increased radiographic progression.Peer reviewedFinal Accepted Versio