Cenozoic evolution of the eastern Black Sea: a test of depth-dependent stretching models

Subsidence analysis of the eastern Black Sea basin suggests that the stratigraphy of this deep, extensional basin can be explained by a predominantly pure-shear stretching history. A strain-rate inversion method that assumes pure-shear extension obtains good fits between observed and predicted stratigraphy. A relatively pure-shear strain distribution is also obtained when a strain-rate inversion algorithm is applied that allows extension to vary with depth without assuming its existence or form. The timing of opening of the eastern Black Sea, which occupied a back-arc position during the closure of the Tethys Ocean, has also been a subject of intense debate; competing theories called for basin opening during the Jurassic, Cretaceous or Paleocene/Eocene. Our work suggests that extension likely continued into the early Cenozoic, in agreement with stratigraphic relationships onshore and with estimates for the timing of arc magmatism. Further basin deepening also appears to have occurred in the last 20 myr. This anomalous subsidence event is focused in the northern part of the basin and reaches its peak at 15–10 Ma. We suggest that this comparatively localized shortening is associated with the northward movement of the Arabian plate. We also explore the effects of paleowater depth and elastic thickness on the results. These parameters are controversial, particularly for deep-water basins and margins, but their estimation is a necessary step in any analysis of the tectonic subsidence record stored in stratigraphy. <br/

Socio‐economic impact classification of alien taxa (SEICAT)

1 Many alien taxa are known to cause socio‐economic impacts by affecting the different constituents of human well‐being (security; material and non‐material assets; health; social, spiritual and cultural relations; freedom of choice and action). Attempts to quantify socio‐economic impacts in monetary terms are unlikely to provide a useful basis for evaluating and comparing impacts of alien taxa because they are notoriously difficult to measure and important aspects of human well‐being are ignored. 2 Here, we propose a novel standardised method for classifying alien taxa in terms of the magnitude of their impacts on human well‐being, based on the capability approach from welfare economics. The core characteristic of this approach is that it uses changes in peoples' activities as a common metric for evaluating impacts on well‐being. 2 Impacts are assigned to one of five levels, from Minimal Concern to Massive, according to semi‐quantitative scenarios that describe the severity of the impacts. Taxa are then classified according to the highest level of deleterious impact that they have been recorded to cause on any constituent of human well‐being. The scheme also includes categories for taxa that are not evaluated, have no alien population, or are data deficient, and a method for assigning uncertainty to all the classifications. To demonstrate the utility of the system, we classified impacts of amphibians globally. These showed a variety of impacts on human well‐being, with the cane toad (Rhinella marina) scoring Major impacts. For most species, however, no studies reporting impacts on human well‐being were found, i.e. these species were data deficient. 2 The classification provides a consistent procedure for translating the broad range of measures and types of impact into ranked levels of socio‐economic impact, assigns alien taxa on the basis of the best available evidence of their documented deleterious impacts, and is applicable across taxa and at a range of spatial scales. The system was designed to align closely with the Environmental Impact Classification for Alien Taxa (EICAT) and the Red List, both of which have been adopted by the International Union of Nature Conservation (IUCN), and could therefore be readily integrated into international practices and policies

Association between Circulating Levels of C-reactive Protein and Positive and Negative Symptoms of Psychosis in Adolescents in a General Population Birth Cohort

Background Schizophrenia is associated with elevated levels of circulating C-reactive protein (CRP) and other inflammatory markers, but it is unclear whether these associations extend to psychotic symptoms occurring in adolescence in the general population. A symptom-based approach may provide important clues for apparent trans-diagnostic effect of inflammation, which is also associated with depression and other psychiatric disorders. Methods Based on data from 2421 participants from the Avon Longitudinal Study of Parents and Children birth cohort, we examined associations of serum CRP levels assessed around age 16 with ten positive and ten negative symptoms of psychosis assessed using questionnaires around age 17, using both individual symptoms and symptom dimension scores as outcomes. Regression models were adjusted for sex, body mass index, depressive symptoms, substance use, and other potential confounders. Results Most prevalent positive symptoms were paranoid ideation (4.8%), visual (4.3%) and auditory (3.5%) hallucinations. Negative symptoms were more strongly correlated with concurrent depressive symptoms (r=0.51; P < 0.001) than positive symptoms (rpb=0.19; P < 0.001). The associations of CRP with positive and negative symptom dimension scores were similar. At individual symptom level, after adjusting for potential confounders including depressive symptoms, CRP was associated with auditory hallucinations (adjusted OR = 2.22; 95% CI, 1.04–4.76) and anhedonia (adjusted OR = 1.13; 95% CI, 1.02–1.26). Conclusions Inflammation is associated with sub-clinical psychotic symptoms in young people in general population. Association of CRP with symptoms commonly shared between mood and psychotic disorders, such as auditory hallucinations and anhedonia, could be one explanation for the apparent trans-diagnostic effect of inflammation

Effects of montmorency tart cherry (L. Prunus Cerasus) consumption on nitric oxide biomarkers and exercise performance

The purpose of this study was to investigate the effects of Montmorency tart cherry juice (MC) on nitric oxide (NO) biomarkers, vascular function and exercise performance. In a randomized, double blind, placebo (PLA) – controlled, crossover study, 10 trained cyclists (mean ± SD; V̇O2peak 59.0 ± 7.0 ml/kg/min) acutely ingested 30 mL of either MC or PLA following dietary restrictions of polyphenol‐rich compounds, and completed 6 min moderate‐ and severe‐intensity cycling bouts 1.5 h post ingestion on two occasions for each experimental condition. The severe‐intensity cycling test was continued to exhaustion on one occasion and immediately followed by a 60 s all‐out sprint on the other occasion. Blood pressure, pulse wave measures, tissue oxygenation index and plasma nitrite concentration were assessed pre and 1.5 h post ingestion. Time to exhaustion was not different between conditions (P > 0.05), but peak power over the first 20 s (363 ± 42 vs. 330 ± 26 W) and total work completed during the 60 s all‐out sprint (21 ± 3 vs. 19 ± 3 kJ) were 10% higher in the MC trial compared to the PLA trial (P 0.05). These results suggest that acute supplementation with MC can lower blood pressure and improve some aspects of exercise performance, specifically end‐sprint performance, in trained cyclists

Are we defending the indefensible? Reflecting on policy and practice around ‘the border’ in plant biosecurity for tree health

Funding: UK BBSRC grant BB/L012030/1 for the project New approaches for the early detection of tree health pests and pathogens.The challenges to forest health from climate change, globalization, contemporary trade practices and new recreational patterns require effective biosecurity. We asked: How is the biosecurity border for tree health understood and enacted by state and non-state actors? What are the consequences for tree health? Semi-structured interviews (N = 10) were conducted with scientists and other relevant actors (N = 21). The border was understood variously as: a biophysical boundary, often the coast; a geopolitical boundary, usually of the European Union; the points of main inspection focus; dispersed nodes of inspection; a ‘pre-border’ outside of UK; or by the location of detection activities. A wide range of state, non-state and hybrid groups are engaged in border practices. These practices have been altered due to trade and climate changes, are subject to cost and resource priorities and reflect particular knowledge flows and the biological nature of the agents. We suggest that there is an ‘everyone’ as well as ‘everywhere’ border that demands clarification of risks, roles and responsibilities, and we offer practical recommendations. We conclude that tree health border challenges are a manifestation of wider sustainability issues that enable us to explore human–nature relationships, democratic engagement and the pursuit of more sustainable futures.Publisher PDFPeer reviewe

Tuberculin skin testing boosts interferon gamma responses to DIVA reagents in Mycobacterium bovis-Infected cattle

ABSTRACT Mycobacterium bovis BCG vaccination sensitizes cattle to bovine tuberculin, which compromises the use of the current bovine tuberculosis (TB) surveillance tests. Although the performance of a blood test (that utilizes antigens expressed by Mycobacterium bovis but not by BCG) capable of discriminating infected from vaccinated animals (DIVA interferon gamma test [DIT]) has been evaluated in naturally infected TB field reactors, there is a need to perform similar analysis in a BCG-vaccinated M. bovis -infected population. Furthermore, we explored different scenarios under which a DIT may be implemented alongside BCG vaccination: (i) serial testing to resolve potential false-positive skin test results or (ii) a standalone test to replace the single intradermal comparative cervical tuberculin (SICCT) skin test. Our results demonstrated significantly better relative test sensitivity when the DIT was evaluated in a serial test scenario. Direct comparison of pre- and post-skin test blood samples revealed that the SICCT test induced significant boosting of the gamma interferon response in M. bovis -infected animals to both the ESAT-6–CFP-10 and Rv3615c peptide cocktails that comprise the DIT, which persisted for the ESAT-6–CFP-10 reagent for at least 14 days. Importantly, no similar boosting effects were observed in noninfected BCG vaccinates, suggesting that DIVA blood testing after a recent skin test would have minimal impact on test specificity. </jats:p

Cannabidivarin is anticonvulsant in mouse and rat in vitro and in seizure models

Summary Background and purpose: Phytocannabinoids in Cannabis sativa have diverse pharmacological targets extending beyond cannabinoid receptors and several exert notable anticonvulsant effects. For the first time, we investigated the anticonvulsant profile of the phytocannabinoid cannabidivarin (CBDV) in vitro and in in vivo seizure models. Experimental approach: The effect of CBDV (1-100μM) on epileptiform local field potentials (LFPs) induced in rat hippocampal brain slices by 4-AP application or Mg2+-free conditions was assessed by in vitro multi-electrode array recordings. Additionally, the anticonvulsant profile of CBDV (50-200 mg kg-1) in vivo was investigated in four rodent seizure models: maximal electroshock (mES) and audiogenic seizures in mice, and pentylenetetrazole (PTZ) and pilocarpine-induced seizures in rat. CBDV effects in combination with commonly-used antiepileptic drugs were investigated in rat seizures. Finally, the motor side effect profile of CBDV was investigated using static beam and gripstrength assays. Key results: CDBV significantly attenuated status epilepticus-like epileptiform LFPs induced by 4-AP and Mg2+-free conditions. CBDV had significant anticonvulsant effects in mES (≥100 mg kg-1), audiogenic (≥50 mg kg-1) and PTZ-induced seizures (≥100 mg kg-1). CBDV alone had no effect against pilocarpine-induced seizures, but significantly attenuated these seizures when administered with valproate or phenobarbital at 200 mg kg-1 CBDV. CBDV had no effect on motor function. Conclusions and Implications: These results indicate that CBDV is an effective anticonvulsant across a broad range of seizure models, does not significantly affect normal motor function and therefore merits further investigation in chronic epilepsy models to justify human trials

Cannabidiol reduces seizures and associated behavioral comorbidities in a range of animal seizure and epilepsy models

Objective Epilepsy is a progressive neurological disease characterized by recurrent seizures and behavioral comorbidities. We investigated the antiseizure effect of cannabidiol (CBD), in a battery of acute seizure models. Additionally, we defined the disease-modifying potential of chronic oral administration of CBD on associated comorbidities in the reduced intensity status epilepticus-spontaneous recurrent seizure (RISE-SRS) model of temporal lobe epilepsy (TLE). Methods We evaluated the acute antiseizure effect of CBD in the maximal electroshock seizure (MES), 6 Hz psychomotor seizure, and pentylenetetrazol (PTZ) acute seizure tests, as well as the corneal kindling model of chronic seizures in mice following intraperitoneal administration. Median effective (ED50) or behavioral toxic dose (TD50) was determined in both mice and rats. Next, we tested an intravenous preparation of CBD (10 mg/kg, single dose) in a rat model of pilocarpine-induced status epilepticus. We defined the effect of chronic CBD administration (200mg/kg, orally) on spontaneous seizures, motor control, gait, and memory function in the rat RISE-SRS model of TLE. Results CBD was effective in a battery of acute seizure models in both mice and rats following intraperitoneal administration. In the pilocarpine induced status epilepticus rat model, CBD attenuated maximum seizure severity following intravenous administration, further demonstrating CBD’s acute antiseizure efficacy in this rat model. We established that oral CBD attenuated the time-dependent increase in seizure burden and improved TLE-associated motor comorbidities of epileptic rats in the RISE-SRS model without affecting gait. Chronic administration of CBD after the onset of SRS ameliorated reference memory and working memory errors of epileptic animals in a spatial learning and memory task. Significance The present study illustrates that CBD is a well-tolerated and effective antiseizure agent and illustrates a potential disease-modifying effect of CBD on both reducing seizure burden and associated comorbidities well-after the onset of symptomatic seizures in a model of TLE

Protocol for the insight study: a randomised controlled trial of single-dose tocilizumab in patients with depression and low-grade inflammation.

INTRODUCTION: Observational studies indicate a potentially causal role for interleukin 6 (IL-6), a proinflammatory cytokine, in pathogenesis of depression, but interventional studies based on patients with depression have not been conducted. Tocilizumab, anti-inflammatory drug, is a humanised monoclonal antibody that inhibits IL-6 signalling and is licensed in the UK for treatment of rheumatoid arthritis. The main objectives of this study are to test whether IL-6 contributes to the pathogenesis of depression and to examine potential mechanisms by which IL-6 affects mood and cognition. A secondary objective is to compare depressed participants with and without evidence of low-grade systemic inflammation. METHODS AND ANALYSIS: This is a proof-of-concept, randomised, parallel-group, double-blind, placebo-controlled clinical trial. Approximately 50 participants with International Classification of Diseases 10th revision (ICD-10) diagnosis of depression who have evidence of low-grade inflammation, defined as serum high-sensitivity C reactive protein (hs-CRP) level ≥3 mg/L, will receive either a single intravenous infusion of tocilizumab or normal saline. Blood samples, behavioural and cognitive measures will be collected at baseline and after infusion around day 7, 14 and 28. The primary outcome is somatic symptoms score around day 14 postinfusion. In addition, approximately, 50 depressed participants without low-grade inflammation (serum hs-CRP level <3 mg/L) will complete the same baseline assessments as the randomised cohort. ETHICS AND DISSEMINATION: The study has been approved by the South Central-Oxford B Research Ethics Committee (REC) (Reference: 18/SC/0118). Study findings will be published in peer-review journals. Findings will be also disseminated by conference/departmental presentations and by social and traditional media. TRIAL REGISTRATION NUMBER: ISRCTN16942542; Pre-results