A systematic review of the neural correlates of sexual minority stress: towards an intersectional minority mosaic framework with implications for a future research agenda

Background: Systemic oppression, particularly towards sexual minorities, continues to be deeply rooted in the bedrock of many societies globally. Experiences with minority stressors (e.g. discrimination, hate-crimes, internalized homonegativity, rejection sensitivity, and microaggressions or everyday indignities) have been consistently linked to adverse mental health outcomes. Elucidating the neural adaptations associated with minority stress exposure will be critical for furthering our understanding of how sexual minorities become disproportionately affected by mental health burdens. Following PRISMA-guidelines, we systematically reviewed published neuroimaging studies that compared neural dynamics among sexual minority and heterosexual populations, aggregating information pertaining to any measurement of minority stress and relevant clinical phenomena. Results: Only 1 of 13 studies eligible for inclusion examined minority stress directly, where all other studies focused on investigating the neurobiological basis of sexual orientation. In our narrative synthesis, we highlight important themes that suggest minority stress exposure may be associated with decreased activation and functional connectivity within the default-mode network (related to the sense-of-self and social cognition), and summarize preliminary evidence related to aberrant neural dynamics within the salience network (involved in threat detection and fear processing) and the central executive network (involved in executive functioning and emotion regulation). Importantly, this parallels neural adaptations commonly observed among individuals with posttraumatic stress disorder (PTSD) in the aftermath of trauma and supports the inclusion of insidious forms of trauma related to minority stress within models of PTSD. Conclusions: Taken together, minority stress may have several shared neuropsychological pathways with PTSD and stress-related disorders. Here, we outline a detailed research agenda that provides an overview of literature linking sexual minority stress to PTSD and insidious trauma, moral affect (including shame and guilt), and mental health risk/resiliency, in addition to racial, ethnic, and gender related minority stress. Finally, we propose a novel minority mosaic framework designed to inform future directions of minority stress neuroimaging research from an intersectional lens

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

Detecting forest response to droughts with global observations of vegetation water content

Droughts in a warming climate have become more common and more extreme, making understanding forest responses to water stress increasingly pressing. Analysis of water stress in trees has long focused on water potential in xylem and leaves, which influences stomatal closure and water flow through the soil-plant-atmosphere continuum. At the same time, changes of vegetation water content (VWC) are linked to a range of tree responses, including fluxes of water and carbon, mortality, flammability, and more. Unlike water potential, which requires demanding in situ measurements, VWC can be retrieved from remote sensing measurements, particularly at microwave frequencies using radar and radiometry. Here, we highlight key frontiers through which VWC has the potential to significantly increase our understanding of forest responses to water stress. To validate remote sensing observations of VWC at landscape scale and to better relate them to data assimilation model parameters, we introduce an ecosystem-scale analog of the pressure-volume curve, the non-linear relationship between average leaf or branch water potential and water content commonly used in plant hydraulics. The sources of variability in these ecosystem-scale pressure-volume curves and their relationship to forest response to water stress are discussed. We further show to what extent diel, seasonal, and decadal dynamics of VWC reflect variations in different processes relating the tree response to water stress. VWC can also be used for inferring belowground conditions-which are difficult to impossible to observe directly. Lastly, we discuss how a dedicated geostationary spaceborne observational system for VWC, when combined with existing datasets, can capture diel and seasonal water dynamics to advance the science and applications of global forest vulnerability to future droughts

Crop Updates 2000 - Weeds

This session covers thirty six papers from different authors: INTRODUCTION, Vanessa Stewart Agriculture Western Australia INTEGRATED WEED MANAGEMENT Effect of seeding density, row spacing and Trifluralin on the competitive ability of Annual Ryegrass in a minimum tillage system, David Minkey, Abul Hashem, Glen Riethmuller and Martin Harries, Agriculture Western Australia High wheat seeding rates coupled with narrow row spacing increases yield and suppresses grass, Peter Newman1 and Cameron Weeks2,1Agronomist, Elders Limited 2Mingenew/Irwin Group Resistant ryegrass management in a wheat – lupin rotation, Abul Hashem, Harmohinder S. Dhammu, Aik Cheam, David Bowran and Terry Piper, Agriculture Western Australia Integrated weed management – Will it work with my rotation? Alexandra Wallace, Agriculture Western Australia Long term herbicide resistance trial – Mingenew, Peter Newman Elders, Cameron Weeks Mingenew-Irwin Group Is two years enough? Bill Roy, Agricultural Consulting and Research Services The fate of ryegrass seed when sheep graze chaff cart heaps, Keith L. Devenish1 and Lisa J. Leaver2 1 Agriculture Western Australia, 2Curtin University of Technology, Muresk Institute of Agriculture Can blanket wiping and crop topping prevent seed set of resistant wild radish and mustard? StAbul Hashem, Harmohinder Dhammu, Vanessa Stewart, Brad Rayner and Mike Collins, Agriculture Western Australia The value of green manuring in the integrated management of ryegrass, Marta Monjardino1,2, David Pannell2, Stephen Powles1 ,1Western Australia Herbicide Resistance Initiative, 2Agricultural and Resource Economics, University of Western Australia Some ways of increasing wheat competitiveness against ryegrass,, Mike Collins Centre for Cropping Systems, Agriculture Western Australia WEED BIOLOGY Understanding and driving weed seed banks to very low levels, Sally Peltzer, Agriculture Western Australi HERBICIDE RESISTANCE Cross resistance of chlorsulfuron-resistant wild radish to imidazolinones, Abul Hashem, Harmohinder Dhammu and David Bowran, Agriculture Western Australia Investigation of suspected triazine resistant ryegrass populations for cross-resistance and multiple resistance to herbicides, Michael Walsh, Charles Boyle and Stephen Powles, Western Australian Herbicide Resistance Initiative, University of Western Australia Genetics and fitness of glyphosate resistant ryegrass, S. Powles1, P. Neve1, D. Lorraine-Colwill2, C. Preston2 ,1WAHRI, University of Western Australia 2 CRC Weed Management Systems, University of Adelaide Managing herbicide resistance – the effect of local extinction of resistance genes, Art Diggle1, Paul B. Neve2, Stephen B. Powles2 ,1Agriculture Western Australia, 2WAHRI, Faculty of Agriculture, University of Western Australia The double knock - the best strategy for conserving glyphosate susceptibility? Paul B. Neve1, Art Diggle2, Stephen B. Powles1,1WAHRI, Faculty of Agriculture, University of Western Australia, 2Agriculture Western Australia Wild radish had evolved resistance to triazines, Abul Hashem, Harmohinder S. Dhammu, David Bowran and Aik Cheam, Agriculture Western Australia Ryegrass resistance in Western Australia – where and how much? Rick Llewellyn and Stephen Powles, Western Australian Herbicide Resistance Initiative, Faculty of Agriculture, University of Western Australia Wild radish herbicide resistance survey, Michael Walsh, Ryan Duane and Stephen Powles, Western Australian Herbicide Resistance Initiative, University of Western Australia Knockdown resistance in the Western Australian wheatbelt – a proposed survey, Paul B. Neve1, Abul Hashem2, Stephen B. Powles1,1Western Australian Herbicide Resistance Initiative, University of Western Australia, 2Agriculture Western Australia Diflufenican resistant wild radish, Aik Cheam, Siew Lee, David Bowran, David Nicholson and Abul Hashem, Agriculture Western Australi Multiple resistance to triazines and diflufenican further complicates wild radish control, Aik Cheam, Siew Lee, David Bowran, David Nicholson and Abul Hashem, Agriculture Western Australia HERBICIDE TOLERANCE 25. Herbicide tolerance of lupins, Terry Piper, Weed Science Group, Agriculture Western Australia 26. Tanjil lupins will tolerate metribuzin under the right conditions, Peter Newman, Agronomist Elders Limited and Cameron Weeks, Mingenew/Irwin Group 27. Herbicide damage does not mean lower yield in Lupins, Peter Carlton, Trials Coordinator, Elders Limited 28. Herbicide tolerance of new pea varieties, Dr Terry Piper, Agriculture Western Australia 29. Herbicide tolerance of (waterlogged) wheat, Dr Terry Piper, Agriculture Western Australia 30. Wheat tolerance trials – Mingenew 1999, Peter Newman1, Cameron Weeks2 and Stewart Smith3,1Elders, Mingenew, 2Mingenew-Irwin Group,3Agriculture Western Australia ISSUES OF TRIFLURALIN USE 31. Trifluralin works better on ryegrass when no-tilling into thick wheat stubbles as granules, or mixed with limesand, Bill Crabtree, WANTFA Scientific Officer 32. Increasing trifluralin rate did not compensate for delaying incorporation, Bill Crabtree, WANTFA Scientific Officer 33. Poor emergence survey, 1999, Terry Piper, Weed Science Group, Agriculture Western Australia HERBICIDES – ISSUES AND OPTIONS 34. AFFINITY 400DF – A new herbicide with a new mode of action (Group G) for Broadleaf Weed Control in Cereals, Gordon Cumming, Technical Officer, Crop Care Australasia 35 Herbicide screening for Marshmallow, David Minkey1 and David Cameron2,1Agriculture Western Australia, 2Elders Ltd, Merredin 36. The control of Capeweed in Clearfield Production System for Canola, Mike Jackson and Scott Paton, Cyanamid Agriculture Pty Ltd 37.Effect of herbicides Tordonä 75D and Lontrelä,used for eradication of Skeleton Weed, on production of Lupins I the following seasons, John R. Peirce and Brad J. Rayner, Agriculture Western Australia INDUSTRY PROTECTION 38. Graingaurd – Opportunities for agribusiness to help protect the West Australian grains industry, Greg Shea, Executive Officer, GrainGuard Agriculture Western Australi

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Characteristics of the Earliest Cross-Neutralizing Antibody Response to HIV-1

Recent cross-sectional analyses of HIV-1+ plasmas have indicated that broadly cross-reactive neutralizing antibody responses are developed by 10%–30% of HIV-1+ subjects. The timing of the initial development of such anti-viral responses is unknown. It is also unknown whether the emergence of these responses coincides with the appearance of antibody specificities to a single or multiple regions of the viral envelope glycoprotein (Env). Here we analyzed the cross-neutralizing antibody responses in longitudinal plasmas collected soon after and up to seven years after HIV-1 infection. We find that anti-HIV-1 cross-neutralizing antibody responses first become evident on average at 2.5 years and, in rare cases, as early as 1 year following infection. If cross-neutralizing antibody responses do not develop during the first 2–3 years of infection, they most likely will not do so subsequently. Our results indicate a potential link between the development of cross-neutralizing antibody responses and specific activation markers on T cells, and with plasma viremia levels. The earliest cross-neutralizing antibody response targets a limited number of Env regions, primarily the CD4-binding site and epitopes that are not present on monomeric Env, but on the virion-associated trimeric Env form. In contrast, the neutralizing activities of plasmas from subjects that did not develop cross-neutralizing antibody responses target epitopes on monomeric gp120 other than the CD4-BS. Our study provides information that is not only relevant to better understanding the interaction of the human immune system with HIV but may guide the development of effective immunization protocols. Since antibodies to complex epitopes that are present on the virion-associated envelope spike appear to be key components of earliest cross-neutralizing activities of HIV-1+ plasmas, then emphasis should be made to elicit similar antibodies by vaccination

Cell-Cell Transmission Enables HIV-1 to Evade Inhibition by Potent CD4bs Directed Antibodies

HIV is known to spread efficiently both in a cell-free state and from cell to cell, however the relative importance of the cell-cell transmission mode in natural infection has not yet been resolved. Likewise to what extent cell-cell transmission is vulnerable to inhibition by neutralizing antibodies and entry inhibitors remains to be determined. Here we report on neutralizing antibody activity during cell-cell transmission using specifically tailored experimental strategies which enable unambiguous discrimination between the two transmission routes. We demonstrate that the activity of neutralizing monoclonal antibodies (mAbs) and entry inhibitors during cell-cell transmission varies depending on their mode of action. While gp41 directed agents remain active, CD4 binding site (CD4bs) directed inhibitors, including the potent neutralizing mAb VRC01, dramatically lose potency during cell-cell transmission. This implies that CD4bs mAbs act preferentially through blocking free virus transmission, while still allowing HIV to spread through cell-cell contacts. Thus providing a plausible explanation for how HIV maintains infectivity and rapidly escapes potent and broadly active CD4bs directed antibody responses in vivo

Implementation of an educational intervention to improve hand washing in primary schools: process evaluation within a randomised controlled trial

Background: Process evaluations are useful for understanding how interventions are implemented in trial settings. This is important for interpreting main trial results and indicating how the intervention might function beyond the trial. The purpose of this study was to examine the reach, dose, fidelity, acceptability, and sustainability of the implementation of an educational hand washing intervention in primary schools, and to explore views regarding acceptability and sustainability of the intervention. Methods: Process evaluation within a cluster randomised controlled trial, including focus groups with pupils aged 6 to 11, semi-structured interviews with teachers and external staff who coordinated the intervention delivery, and school reports and direct observations of the intervention delivery. Results: The educational package was delivered in 61.4% of schools (85.2% of intervention schools, 37.8% of control schools following completion of the trial). Teachers and pupils reacted positively to the intervention, although concerns were raised about the age-appropriateness of the resources. Teachers adapted the resources to suit their school setting and pupils. Staff coordinating the intervention delivery had limited capacity to follow up and respond to schools. Conclusions: The hand washing intervention was acceptable to schools, but its reach outside of a randomised trial, evidenced in the low proportion of schools in the control arm who received it after the trial had ended, suggests that the model of delivery may not be sustainable.Catherine R Chittleborough, Alexandra L Nicholson, Elaine Young, Sarah Bell and Rona Campbel

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer