Challenges of achieving good environmental status in the Northeast Atlantic

The sustainable exploitation of marine ecosystem services is dependent on achieving and maintaining an adequate ecosystem state to prevent undue deterioration. Within the European Union, the Marine Strategy Framework Directive (MSFD) requires member states to achieve Good Environmental Status (GEnS), specified in terms of 11 descriptors. We analyzed the complexity of social-ecological factors to identify common critical issues that are likely to influence the achievement of GEnS in the Northeast Atlantic (NEA) more broadly, using three case studies. A conceptual model developed using a soft systems approach highlights the complexity of social and ecological phenomena that influence, and are likely to continue to influence, the state of ecosystems in the NEA. The development of the conceptual model raised four issues that complicate the implementation of the MSFD, the majority of which arose in the Pressures and State sections of the model: variability in the system, cumulative effects, ecosystem resilience, and conflicting policy targets. The achievement of GEnS targets for the marine environment requires the recognition and negotiation of trade-offs across a broad policy landscape involving a wide variety of stakeholders in the public and private sectors. Furthermore, potential cumulative effects may introduce uncertainty, particularly in selecting appropriate management measures. There also are endogenous pressures that society cannot control. This uncertainty is even more obvious when variability within the system, e.g., climate change, is accounted for. Also, questions related to the resilience of the affected ecosystem to specific pressures must be raised, despite a lack of current knowledge. Achieving good management and reaching GEnS require multidisciplinary assessments. The soft systems approach provides one mechanism for bringing multidisciplinary information together to look at the problems in a different light

Radiographers' knowledge, attitudes and expectations of artificial intelligence in medical imaging

Introduction: Artificial intelligence (AI) is increasingly utilised in medical imaging systems and processes, and radiographers must embrace this advancement. This study aimed to investigate perceptions, knowledge, and expectations towards integrating AI into medical imaging amongst a sample of radiographers and determine the current state of AI education within the community. Methods: A cross-sectional online quantitative study targeting radiographers based in Europe was conducted over ten weeks. Captured data included demographical information, participants’ perceptions and understanding of AI, expectations of AI and AI-related educational backgrounds. Both descriptive and inferential statistical techniques were used to analyse the obtained data. Results: A total of 96 valid responses were collected. Of these, 64% correctly identified the true definition of AI from a range of options, but fewer (37%) fully understood the difference between AI, machine learning and deep learning. The majority of participants (83%) agreed they were excited about the advancement of AI, though a level of apprehensiveness remained amongst 29%. A severe lack of education on AI was noted, with only 8% of participants having received AI teachings in their pre-registration qualification. Conclusion: Overall positive attitudes towards AI implementation were observed. The slight apprehension may stem from the lack of technical understanding of AI technologies and AI training within the community. Greater educational programs focusing on AI principles are required to help increase European radiography workforce engagement and involvement in AI technologies. Implications for practice: This study offers insight into the current perspectives of European based radiographers on AI in radiography to help facilitate the embracement of AI technology and convey the need for AI-focused education within the profession

An evaluation of information online on artificial intelligence in medical imaging

Background: Opinions seem somewhat divided when considering the effect of artificial intelligence (AI) on medical imaging. The aim of this study was to characterise viewpoints presented online relating to the impact of AI on the field of radiology and to assess who is engaging in this discourse. Methods: Two search methods were used to identify online information relating to AI and radiology. Firstly, 34 terms were searched using Google and the first two pages of results for each term were evaluated. Secondly, a Rich Search Site (RSS) feed evaluated incidental information over 3 weeks. Webpages were evaluated and categorized as having a positive, negative, balanced, or neutral viewpoint based on study criteria. Results: Of the 680 webpages identified using the Google search engine, 248 were deemed relevant and accessible. 43.2% had a positive viewpoint, 38.3% a balanced viewpoint, 15.3% a neutral viewpoint, and 3.2% a negative viewpoint. Peer-reviewed journals represented the most common webpage source (48%), followed by media (29%), commercial sources (12%), and educational sources (8%). Commercial webpages had the highest proportion of positive viewpoints (66%). Radiologists were identified as the most common author group (38.9%). The RSS feed identified 177 posts of which were relevant and accessible. 86% of posts were of media origin expressing positive viewpoints (64%). Conclusion: The overall opinion of the impact of AI on radiology presented online is a positive one. Consistency across a range of sources and author groups exists. Radiologists were significant contributors to this online discussion and the results may impact future recruitment

A decade of theory as reflected in Psychological Science (2009–2019)

The dominant belief is that science progresses by testing theories and moving towards theoretical consensus. While it’s implicitly assumed that psychology operates in this manner, critical discussions claim that the field suffers from a lack of cumulative theory. To examine this paradox, we analysed research published in Psychological Science from 2009–2019 (N = 2,225). We found mention of 359 theories in-text, most were referred to only once. Only 53.66% of all manuscripts included the word theory, and only 15.33% explicitly claimed to test predictions derived from theories. We interpret this to suggest that the majority of research published in this flagship journal is not driven by theory, nor can it be contributing to cumulative theory building. These data provide insight into the kinds of research psychologists are conducting and raises questions about the role of theory in the psychological sciences

TLR4 and NKT Cell Synergy in Immunotherapy against Visceral Leishmaniasis

NKT cells play an important role in autoimmune diseases, tumor surveillance, and infectious diseases, providing in most cases protection against infection. NKT cells are reactive to CD1d presented glycolipid antigens. They can modulate immune responses by promoting the secretion of type 1, type 2, or immune regulatory cytokines. Pathogen-derived signals to dendritic cells mediated via Toll like Receptors (TLR) can be modulated by activated invariant Natural Killer T (iNKT) cells. The terminal β-(1–4)-galactose residues of glycans can modulate host responsiveness in a T helper type-1 direction via IFN-γ and TLRs. We have attempted to develop a defined immunotherapeutic, based on the cooperative action of a TLR ligand and iNKT cell using a mouse model of visceral leishmaniasis. We evaluated the anti-Leishmania immune responses and the protective efficacy of the β-(1–4)-galactose terminal NKT cell ligand glycosphingophospholipid (GSPL) antigen of L. donovani parasites. Our results suggest that TLR4 can function as an upstream sensor for GSPL and provoke intracellular inflammatory signaling necessary for parasite killing. Treatment with GSPL was able to induce a strong effective T cell response that contributed to effective control of acute parasite burden and led to undetectable parasite persistence in the infected animals. These studies for the first time demonstrate the interactions between a TLR ligand and iNKT cell activation in visceral leishmaniasis immunotherapeutic

Nucleotide-Oligomerization-Domain-2 Affects Commensal Gut Microbiota Composition and Intracerebral Immunopathology in Acute Toxoplasma gondii Induced Murine Ileitis

Background Within one week following peroral high dose infection with Toxoplasma (T.) gondii, susceptible mice develop non-selflimiting acute ileitis due to an underlying Th1-type immunopathology. The role of the innate immune receptor nucleotide-oligomerization-domain-2 (NOD2) in mediating potential extra-intestinal inflammatory sequelae including the brain, however, has not been investigated so far. Methodology/Principal Findings Following peroral infection with 100 cysts of T. gondii strain ME49, NOD2-/- mice displayed more severe ileitis and higher small intestinal parasitic loads as compared to wildtype (WT) mice. However, systemic (i.e. splenic) levels of pro-inflammatory cytokines such as TNF-α and IFN-γ were lower in NOD2-/- mice versus WT controls at day 7 p.i. Given that the immunopathological outcome might be influenced by the intestinal microbiota composition, which is shaped by NOD2, we performed a quantitative survey of main intestinal bacterial groups by 16S rRNA analysis. Interestingly, Bifidobacteria were virtually absent in NOD2-/- but not WT mice, whereas differences in remaining bacterial species were rather subtle. Interestingly, more distinct intestinal inflammation was accompanied by higher bacterial translocation rates to extra- intestinal tissue sites such as liver, spleen, and kidneys in T. gondii infected NOD2-/- mice. Strikingly, intracerebral inflammatory foci could be observed as early as seven days following T. gondii infection irrespective of the genotype of animals, whereas NOD2-/- mice exhibited higher intracerebral parasitic loads, higher F4/80 positive macrophage and microglia numbers as well as higher IFN-γ mRNA expression levels as compared to WT control animals. Conclusion/Significance NOD2 signaling is involved in protection of mice from T. gondii induced acute ileitis. The parasite-induced Th1-type immunopathology at intestinal as well as extra-intestinal sites including the brain is modulated in a NOD2-dependent manner

Neuroadaptations in Human Chronic Alcoholics: Dysregulation of the NF-κB System

Anna Ökvist is with Karolinska Institute, Sofia Johansson is with Karolinska Institute, Alexander Kuzmin is with Karolinska Institute, Igor Bazov is with Karolinska Institute, Roxana Merino-Martinez is with Karolinska Institute, Igor Ponomarev is with UT Austin, R. Dayne Mayfield is with UT Austin, R. Adron Harris is with UT Austin, Donna Sheedy is with University of Sydney, Therese Garrick is with University of Sydney, Clive Harper is with University of Sydney, Yasmin L. Hurd is with Mount Sinai School of Medicine, Lars Terenius is with Karolinska Institute, Tomas J. Ekström is with Karolinska Institute, Georgy Bakalkin is with Karolinska Institute and Uppsala University, Tatjana Yakovleva is with Karolinska Institute and Uppsala University.Background -- Alcohol dependence and associated cognitive impairments apparently result from neuroadaptations to chronic alcohol consumption involving changes in expression of multiple genes. Here we investigated whether transcription factors of Nuclear Factor-kappaB (NF-κB) family, controlling neuronal plasticity and neurodegeneration, are involved in these adaptations in human chronic alcoholics. Methods and Findings -- Analysis of DNA-binding of NF-κB (p65/p50 heterodimer) and the p50 homodimer as well as NF-κB proteins and mRNAs was performed in postmortem human brain samples from 15 chronic alcoholics and 15 control subjects. The prefrontal cortex involved in alcohol dependence and cognition was analyzed and the motor cortex was studied for comparison. The p50 homodimer was identified as dominant κB binding factor in analyzed tissues. NF-κB and p50 homodimer DNA-binding was downregulated, levels of p65 (RELA) mRNA were attenuated, and the stoichiometry of p65/p50 proteins and respective mRNAs was altered in the prefrontal cortex of alcoholics. Comparison of a number of p50 homodimer/NF-κB target DNA sites, κB elements in 479 genes, down- or upregulated in alcoholics demonstrated that genes with κB elements were generally upregulated in alcoholics. No significant differences between alcoholics and controls were observed in the motor cortex. Conclusions -- We suggest that cycles of alcohol intoxication/withdrawal, which may initially activate NF-κB, when repeated over years downregulate RELA expression and NF-κB and p50 homodimer DNA-binding. Downregulation of the dominant p50 homodimer, a potent inhibitor of gene transcription apparently resulted in derepression of κB regulated genes. Alterations in expression of p50 homodimer/NF-κB regulated genes may contribute to neuroplastic adaptation underlying alcoholism.This work was supported by grants from the AFA Forsäkring to AK, YLH, TJE and GB, the Research Foundation of the Swedish Alcohol Retail Monopoly (SRA) and Karolinska Institutet to AK, TJE and GB, and the Swedish Science Research Council and the Swedish National Drug Policy Coordinator to GB. The Australian Brain Donor Programs NSW Tissue Resource Centre was supported by The University of Sydney, National Health and Medical Research Council of Australia, Neuroscience Institute of Schizophrenia and Allied Disorders, National Institute of Alcohol Abuse and Alcoholism and NSW Department of Health.Waggoner Center for Alcohol and Addiction Researc

Androgen Receptor Drives Cellular Senescence

The accepted androgen receptor (AR) role is to promote proliferation and survival of prostate epithelium and thus prostate cancer progression. While growth-inhibitory, tumor-suppressive AR effects have also been documented, the underlying mechanisms are poorly understood. Here, we for the first time link AR anti-cancer action with cell senescence in vitro and in vivo. First, AR-driven senescence was p53-independent. Instead, AR induced p21, which subsequently reduced ΔN isoform of p63. Second, AR activation increased reactive oxygen species (ROS) and thereby suppressed Rb phosphorylation. Both pathways were critical for senescence as was proven by p21 and Rb knock-down and by quenching ROS with N-Acetyl cysteine and p63 silencing also mimicked AR-induced senescence. The two pathways engaged in a cross-talk, likely via PML tumor suppressor, whose localization to senescence-associated chromatin foci was increased by AR activation. All these pathways contributed to growth arrest, which resolved in senescence due to concomitant lack of p53 and high mTOR activity. This is the first demonstration of senescence response caused by a nuclear hormone receptor

Examining the generalizability of research findings from archival data

This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability—for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples

Multiple Loci Are Associated with White Blood Cell Phenotypes

White blood cell (WBC) count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count—6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count—17q21; basophil count- 3p21 near RPN1 and C3orf27; lymphocyte count—6p21, 19p13 at EPS15L1; monocyte count—2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2), including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression- and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across populations of diverse ancestral backgrounds