Rates, perceptions and predictors of depression, anxiety and Post Traumatic Stress Disorder (PTSD)-like symptoms about Covid-19 in adolescents

Increasing evidence has shown that the Covid-19 outbreak, and subsequent school closures and exam cancellations that followed, has impacted adolescent mental health. The current cross-sectional study examined rates of depression, anxiety and Post Traumatic Stress Disorder (PTSD)-like symptoms about Covid-19 in adolescents and whether current or past mental health support, additional support in school, keyworker status, poorer household relationships since the outbreak of Covid-19 or reduced physical activity were associated with elevated levels of depression, anxiety or PTSD-like symptoms. Lastly, it examined perceived changes in mental health due to the Covid-19 pandemic, school closures and the cancellation of exams. A total of 899 adolescents (14-18 years) took part in the 'in isolation instead of in school' (INISS) project. Findings indicated that older adolescents, females, those who currently or previously received mental health support or additional support in school and adolescents who reported poorer relationships at home since Covid-19 were more likely to meet clinical threshold levels for their mental health. Adolescents highlighted worsening of their mental health due to Covid-19 and school closures with mixed positive and negative impact of exam cancellations. Adolescents experiencing clinical threshold levels of depression and anxiety uniquely reported worsening of their mental health since the Covid-19 pandemic, school closures and exam cancellations. Understanding the rates, perceptions and factors associated with increases in depression, anxiety and PTSD-like symptoms in adolescents during the Covid-19 pandemic will inform national policy in supporting adolescent mental health and recovery from the Covid-19 pandemic

Bifidobacterium breve MRx0004 protects against airway inflammation in a severe asthma model by suppressing both neutrophil and eosinophil lung infiltration

All authors were employees of (or in the case of MID, seconded full-time to) 4D Pharma Research Ltd while engaged in the research project. This work was supported by funding provided by 4D Pharma PLC. 4D Pharma Research Ltd owns a family of patent applications which are pending internationally which are derived from International Patent Publication No. WO2016/203223 which protect the treatment of severe asthma using MRx0004. George Grant, Angela Patterson, Imke Mulder, Seanin McCluskey and Emma Raftis are named as inventors for this patent family. The authors declare no other competing interests.Peer reviewedPublisher PD

In vivo and in vitro toxicity of cobalt in the heart

Wear debris from cobalt/chromium (Co/Cr) alloy metal-on-metal bearings in prosthetic hip replacements has created a significant internal source of cobalt exposure in these patients. Co toxicity is suspected to contribute to severe systemic adverse effects, including cardiac and CNS effects, in patients with high circulating Co concentrations. This study investigated the effects of chronic Co exposure to rats (1mg/kg i.p. CoCl2, daily, for 28 days) and Co uptake into primary adult rat cardiac fibroblasts (CFs). Co treatment was associated with accumulation into various organs of the body and significant increases in Co levels were detected in liver, kidney and heart. Echocardiography showed functional changes that correlated with compromised cardiac contractility. Fractional shortening was significantly reduced in CoCl2-treated rats following 28 days treatment compared to the control group (54.01±0.90% and 60.29±0.53% respectively), providing evidence of contractile dysfunction. Cellular studies examined uptake of CoCl2 into both CFs and 3T3 fibroblasts using inductively coupled plasma mass spectrometry (ICP-MS) to measure intracellular metal content. The range of Co uptake increased proportionally (0-50 µg/L) for the 3T3 cells, as well as for the CFs (about 0-120 µg/L) when the CoCl2 concentration in the medium was increased between 0 and 72 mg/L. Uptake of Co into CFs was significantly greater than into 3T3 cells. The greater accumulation of CoCl2 into CFs suggests Co ions in vivo could accumulate in these cells, leading to functional consequences on cardiac performance. Future work will focus on determining the underlying uptake mechanism which could have important therapeutic implications

Cobalt administration causes reduced contractility with parallel increases in TRPC6 and TRPM7 transporter protein expression in adult rat hearts

Exposure to circulating cobalt (Co2+) in patients with metal-on-metal orthopaedic hip implants has been linked to cardiotoxicity but the underlying mechanism(s) remain undefined. The aim of the current study was to examine the effects of Co2+ on the heart in vivo and specifically on cardiac fibroblasts in vitro. Adult male rats were treated with CoCl2 (1 mg/kg) for either 7 days or 28 days. Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure Co2+uptake into various organs of the body. Co2+ accumulated in the heart over time with significant levels evident after only 7 days of treatment. There was no evidence of cardiac remodelling following Co2+ treatment as assessed by heart weight:body weight and left ventricular weight:body weight. However, a decrease in fractional shortening, as measured using echocardiography, was observed after 28 days of Co2+ treatment. This was accompanied by increased protein expression of the ion transient receptor potential (TRP) channels TRPC6 and TRPM7 as assessed by quantitative immunoblotting of whole cardiac homogenates. Uptake of Co2+ specifically into rat cardiac fibroblasts was measured over 72 h and was shown to dramatically increase with increasing concentrations of applied CoCl2. Expression levels of TRPC6 and TRPM7 proteins were both significantly elevated in these cells following Co2+treatment. In conclusion, Co2+ rapidly accumulates to significant levels in the heart causing compromised contractility in the absence of any overt cardiac remodelling. TRPC6 and TRPM7 expression levels are significantly altered in the heart following Co2+ treatment and this may contribute to the Co2+-induced cardiotoxicity observed over time

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

A case study in the use of theory revision in requirements validation

Research emanating from Artificial Intelligence has throughout its history contributed to techniques and ideas in Software Engineering. We describe in this paper a case study showing the use of theory revision to the refinement of a formally specified requirements model. In a previous project we were contracted to create a precise model of the complex criteria governing the separation of aircraft profiles in Atlantic Airspace. During that work it became clear that the (automated) validation of the model was of the utmost importance, and in our current project we have used machine learning tools to provide extra support in bug identification, bug removal and maintenance of such a requirements model. In this paper we give an overview of the domain, identify a relevant learning bias which makes search for revisions tractable, and describe a systematic approach for the application of theory revision to such a model. We illustrate the approach with results of experiments where theory revisi..

Acquisition of Object-Centred Domain Models from Planning Examples

The problem of formulating knowledge bases containing action schema is a central concern in knowledge engineering for AI Planning. This paper describes LOCM, a system which carries out the automated induction of action schema from sets of example plans. Each plan is assumed to be a sound sequence of actions; each action in a plan is stated as a name and a list of objects that the action refers to. LOCM exploits the assumption that actions change the state of objects, and require objects to be in a certain state before they can be executed. The novelty of LOCM is that it can induce action schema without being provided with any information about predicates or initial, goal or intermediate state descriptions for the example action sequences. In this paper we describe the implemented LOCM algorithm, and analyse its performance by its application to the induction of domain models for several domains. To evaluate the algorithm, we used random action sequences from existing models of domains, as well as solutions to past IPC problems

Towards the Automated Debugging and Maintenance of Logic-based Requirements Models

In this paper we describe a tools environment which automates the validation and maintenance of a requirements model written in many-sorted first order logic. We focus on: a translator, that produces an executable form of the model; blame assignment functions, which input batches of mis-classified tests (i.e. training examples) and output likely faulty parts of the model; and a theory reviser, which inputs the faulty parts and examples and outputs suggested revisions to the model. In particular, we concentrate on the problems encountered when applying these tools to a real application: a requirements model containing air traffic control separation standards, operating methods and airspace information

Towards inducing HTN domain models from examples

Domain modelling for AI Planning can be a complex process especially if there is a large number of objects or actions or both to be modelled. This task can be facilitated by tools which induce operators or methods from examples. Further, large and complex domains are more easily constructed if domain languages are used which allow for hierarchical decomposition of domain components. Examples of such a decomposition are object class hierarchies and method hierarchies. This paper describes ongoing work which aims to produce algorithms which learn effective hierarchical decompositions from examples