Psychophysical and Psychological Factors Affecting Recovery from Acute Balance Disorders

Patients with acute vestibular neuritis are traditionally investigated with caloric or rotational examination of the vestibular-ocular reflex. However, clinical outcome is poorly predicted by such vestibular reflex assessments. We hypothesised that symptomatic recovery would depend upon higher order visuo-vestibular compensatory mechanisms. Thirty-one patients were studied in the acute and recovery phases of vestibular neuritis (median 2 days and 10 weeks, respectively). Patients underwent examination of vestibulo-ocular and vestibular-perceptual responses, at threshold and supra-threshold levels. Supra-threshold stimuli (90°/s velocity step rotations) allowed quantification of vestibulo-ocular and vestibulo-perceptual time constants. Additional measures of visual dependency (rod-and-disc task), dizziness symptom load (Vertigo Symptom Scale and Dizziness Handicap Inventory) and psychological factors (including - autonomic arousal, anxiety, depression, fear of bodily sensations) were obtained. Vestibulo-perceptual and vestibulo-ocular thresholds were raised and asymmetric acutely and remained slightly elevated and asymmetric at recovery. Acutely, supra-threshold vestibulo-ocular time constants were shortened and asymmetric. In contrast, perceptual responses were reduced but notably symmetrical. At recovery, vestibulo-ocular supra-threshold responses remained abnormal but perceptual supra-threshold responses normalised. Visual dependency was significantly elevated above normals in both acute and recovery stages. Vertigo symptom recovery was significantly predicted by acute levels of visual dependency (p=0.002), autonomic anxiety (p=0.004). A number of measures were associated with vertigo symptoms at recovery, in addition to visual dependency (p=0.012) and autonomic anxiety (p<0.001), including - anxiety and depression (p<0.003), fear of body sensations (p=0.033), vestibular perceptual thresholds (p=0.017) and caloric canal paresis (p=0.001). Factor Analysis revealed a strong association between clinical outcome, visual dependency and psychological factors, all loading on a single component accounting for 59.15% of the variance. The bilateral suppression of supra-threshold vestibular perception observed acutely represents a hitherto unrecognised central adaptive ‘anti-vertiginous’ mechanism. However, poor symptomatic recovery is best predicted by increased visual dependency and psychological factors. The findings show that long term recovery from unilateral vestibular deficit is mediated by central compensatory mechanisms, including multi-sensory integration and psychological processing

Exploring open cheminformatics approaches for categorizing per-and polyfluoroalkyl substances (PFASs)

Per- and polyfluoroalkyl substances (PFASs) are a large and diverse class of chemicals of great interest due to their wide commercial applicability, as well as increasing public concern regarding their adverse impacts. A common terminology for PFASs was recommended in 2011, including broad categorization and detailed naming for many PFASs with rather simple molecular structures. Recent advancements in chemical analysis have enabled identification of a wide variety of PFASs that are not covered by this common terminology. The resulting inconsistency in categorizing and naming of PFASs is preventing efficient assimilation of reported information. This article explores how a combination of expert knowledge and cheminformatics approaches could help address this challenge in a systematic manner. First, the “splitPFAS” approach was developed to systematically subdivide PFASs (for eventual categorization) following a CnF2n+1–X–R pattern into their various parts, with a particular focus on 4 PFAS categories where X is CO, SO2, CH2 and CH2CH2. Then, the open, ontology-based “ClassyFire” approach was tested for potential applicability to categorizing and naming PFASs using five scenarios of original and simplified structures based on the “splitPFAS” output. This workflow was applied to a set of 770 PFASs from the latest OECD PFAS list. While splitPFAS categorized PFASs as intended, the ClassyFire results were mixed. These results reveal that open cheminformatics approaches have the potential to assist in categorizing PFASs in a consistent manner, while much development is needed for future systematic naming of PFASs. The “splitPFAS” tool and related code are publicly available, and include options to extend this proof-of-concept to encompass further PFASs in the future

Competitive outreach in the 21st century: Why we need conservation marketing

AbstractAddressing impacts from human activities requires the change of current practices. However, reaching a target audience about conservation issues and influencing their behaviour is not easy in a world where people are continually bombarded with information, and distractions are permanently available. Although not typically considered to be part of the conservation science toolbox, marketing techniques were designed in the commercial sector to identify and influence human preferences and behaviour by placing target audiences at the core of the marketing process. It thus seems reasonable that the same marketing principles and tools could and should be used to address pressing conservation issues. In this manuscript, we provide an introduction to the main objectives of marketing and illustrate how these can be applied to conservation and animal welfare issues. To that end we offer two examples: Project Ocean, where a major UK retailer joined forces with the Zoological Society of London to influence consumer behaviour around seafood; and Blackfish, which coupled social media with an award-winning documentary to create a discussion around the welfare of large cetaceans in captivity. Without the ability to influence human behaviour, a conservationists' role will likely be limited to that of describing the loss of biodiversity and the decline of the environment. We thus hope that conservation practitioners can embrace marketing as a fundamental component of the conservation toolbox

Discovery of os cordis in the cardiac skeleton of chimpanzees (Pan troglodytes)

© 2020, The Author(s). Cardiovascular diseases, especially idiopathic myocardial fibrosis, is one of the most significant causes of morbidity and mortality in captive great apes. This study compared the structure and morphology of 16 hearts from chimpanzees (Pan troglodytes) which were either healthy or affected by myocardial fibrosis using X-ray microtomography. In four hearts, a single, hyperdense structure was detected within the right fibrous trigone of the cardiac skeleton. High resolution scans and histopathology revealed trabecular bones in two cases, hyaline cartilage in another case and a focus of mineralised fibro-cartilaginous metaplasia with endochondral ossification in the last case. Four other animals presented with multiple foci of ectopic calcification within the walls of the great vessels. All hearts affected by marked myocardial fibrosis presented with bone or cartilage formation, and increased collagen levels in tissues adjacent to the bone/cartilage, while unaffected hearts did not present with os cordis or cartilago cordis. The presence of an os cordis has been described in some ruminants, camelids, and otters, but never in great apes. This novel research indicates that an os cordis and cartilago cordis is present in some chimpanzees, particularly those affected by myocardial fibrosis, and could influence the risk of cardiac arrhythmias and sudden death

Strengthen the European collaborative environmental research to meet European policy goals for achieving a sustainable, non-toxic environment

To meet the United Nations (UN) sustainable development goals and the European Union (EU) strategy for a non-toxic environment, water resources and ecosystems management require cost-efficient solutions for prevailing complex contamination and multiple stressor exposures. For the protection of water resources under global change conditions, specific research needs for prediction, monitoring, assessment and abatement of multiple stressors emerge with respect to maintaining human needs, biodiversity, and ecosystem services. Collaborative European research seems an ideal instrument to mobilize the required transdisciplinary scientific support and tackle the large-scale dimension and develop options required for implementation of European policies. Calls for research on minimizing society’s chemical footprints in the water–food–energy–security nexus are required. European research should be complemented with targeted national scientific funding to address specific transformation pathways and support the evaluation, demonstration and implementation of novel approaches on regional scales. The foreseeable pressure developments due to demographic, economic and climate changes require solution-oriented thinking, focusing on the assessment of sustainable abatement options and transformation pathways rather than on status evaluation. Stakeholder involvement is a key success factor in collaborative projects as it allows capturing added value, to address other levels of complexity, and find smarter solutions by synthesizing scientific evidence, integrating governance issues, and addressing transition pathways. This increases the chances of closing the value chain by implementing novel solutions. For the water quality topic, the interacting European collaborative projects SOLUTIONS, MARS and GLOBAQUA and the NORMAN network provide best practice examples for successful applied collaborative research including multi-stakeholder involvement. They provided innovative conceptual, modelling and instrumental options for future monitoring and management of chemical mixtures and multiple stressors in European water resources. Advancement of EU water framework directive-related policies has therefore become an option

Adverse outcomes in older adults attending emergency departments: a systematic review and meta-analysis of the Identification of Seniors At Risk (ISAR) screening tool

Background older adults are frequent users of emergency services and demonstrate high rates of adverse outcomes following emergency care. Objective to perform a systematic review and meta-analysis of the Identification of Seniors At Risk (ISAR) screening tool, to determine its predictive value in identifying adults ≥65 years at risk of functional decline, unplanned emergency department (ED) readmission, emergency hospitalisation or death within 180 days after index ED visit/hospitalisation. Methods a systematic literature search was conducted in PubMed, EMBASE, CINAHL, EBSCO and the Cochrane Library to identify validation and impact analysis studies of the ISAR tool. A pre-specified ISAR score of ≥2 (maximum score 6 points) was used to identify patients at high risk of adverse outcomes. A bivariate random effects model generated pooled estimates of sensitivity and specificity. Statistical heterogeneity was explored and methodological quality was assessed using validated criteria. Results thirty-two validation studies (n = 12,939) are included. At ≥2, the pooled sensitivity of the ISAR for predicting ED return, emergency hospitalisation and mortality at 6 months is 0.80 (95% confidence interval (CI) 0.70–0.87), 0.82 (95% CI 0.74–0.88) and 0.87 (95% CI 0.75–0.94), respectively, with a pooled specificity of 0.31 (95% CI 0.24–0.38), 0.32 (95% CI 0.24–0.41) and 0.35 (95% CI 0.26–0.44). Similar values are demonstrated at 30 and 90 days. Three heterogeneous impact analysis studies examined the clinical implementation of the ISAR and reported mixed findings across patient and process outcomes. Conclusion the ISAR has modest predictive accuracy and may serve as a decision-making adjunct when determining which older adults can be safely discharged

Pharmacological validation of targets regulating CD14 during macrophage differentiation

The signalling receptor for LPS, CD14, is a key marker of, and facilitator for, pro-inflammatory macrophage function. Pro-inflammatory macrophage differentiation remains a process facilitating a broad array of disease pathologies, and has recently emerged as a potential target against cytokine storm in COVID19. Here, we perform a whole-genome CRISPR screen to identify essential nodes regulating CD14 expression in myeloid cells, using the differentiation of THP-1 cells as a starting point. This strategy uncovers many known pathways required for CD14 expression and regulating macrophage differentiation while additionally providing a list of novel targets either promoting or limiting this process. To speed translation of these results, we have then taken the approach of independently validating hits from the screen using well-curated small molecules. In this manner, we identify pharmacologically tractable hits that can either increase CD14 expression on non-differentiated monocytes or prevent CD14 upregulation during macrophage differentiation. An inhibitor for one of these targets, MAP2K3, translates through to studies on primary human monocytes, where it prevents upregulation of CD14 following M-CSF induced differentiation, and pro-inflammatory cytokine production in response to LPS. Therefore, this screening cascade has rapidly identified pharmacologically tractable nodes regulating a critical disease-relevant process