Posttraumatic stress disorder following asthma attack (post-asthma attack PTSD) and psychiatric co-morbidity: The impact of alexithymia and coping

This study investigated the prevalence of post-asthma attack posttraumatic stress disorder (PTSD) and the severity of psychiatric co-morbidity among a group of college students and whether alexithymia and coping strategies would relate to health outcomes. This is a cross-sectional study in which 156 college students who had previously experienced asthma attack were recruited. They completed a demographic page, Asthma Symptom Checklist, PTSD Checklist, General Health Questionnaire-28, Toronto Alexithymia Scale and the COPE. They were also matched with 141 students without asthma. The results showed that 3% met the criteria for full-PTSD, 44% for partial and 53% for no-PTSD. There were no significant differences between the asthma and control groups in severity of psychiatric co-morbid symptoms. Path analyses showed that asthma severity was significantly correlated with PTSD and psychiatric co-morbidity. It was also correlated with alexithymia which was in turn associated with psychiatric co-morbidity but not PTSD. Coping strategies were not correlated with health outcomes. To conclude, people can develop PTSD symptoms and degrees of psychiatric co-morbid symptoms after suffering asthma attack. The severity of these symptoms relates to people\u27s perceptions of asthma severity and alexithymia. © 2012 Elsevier Ltd

Fungal plant pathogen “mutagenomics” reveals tagged and untagged mutations in Zymoseptoria tritici and identifies SSK2 as key morphogenesis and stress-responsive virulence factor

“Mutagenomics” is the combination of random mutagenesis, phenotypic screening, and whole-genome re-sequencing to uncover all tagged and untagged mutations linked with phenotypic changes in an organism. In this study, we performed a mutagenomics screen on the wheat pathogenic fungus Zymoseptoria tritici for altered morphogenetic switching and stress sensitivity phenotypes using Agrobacterium-mediated “random” T-DNA mutagenesis (ATMT). Biological screening identified four mutants which were strongly reduced in virulence on wheat. Whole genome re-sequencing defined the positions of the T-DNA insertion events and revealed several unlinked mutations potentially affecting gene functions. Remarkably, two independent reduced virulence mutant strains, with similarly altered stress sensitivities and aberrant hyphal growth phenotypes, were found to have a distinct loss of function mutations in the ZtSSK2 MAPKKK gene. One mutant strain had a direct T-DNA insertion affecting the predicted protein’s N-terminus, while the other possessed an unlinked frameshift mutation towards the C-terminus. We used genetic complementation to restore both strains’ wild-type (WT) function (virulence, morphogenesis, and stress response). We demonstrated that ZtSSK2 has a non-redundant function with ZtSTE11 in virulence through the biochemical activation of the stress-activated HOG1 MAPK pathway. Moreover, we present data suggesting that SSK2 has a unique role in activating this pathway in response to specific stresses. Finally, dual RNAseq-based transcriptome profiling of WT and SSK2 mutant strains revealed many HOG1-dependent transcriptional changes in the fungus during early infection and suggested that the host response does not discriminate between WT and mutant strains during this early phase. Together these data define new genes implicated in the virulence of the pathogen and emphasise the importance of a whole genome sequencing step in mutagenomic discovery pipelines

Anti-nausea effects and pharmacokinetics of ondansetron, maropitant and metoclopramide in a low-dose cisplatin model of nausea and vomiting in the dog: a blinded crossover study

Nausea is a subjective sensation which is difficult to measure in non-verbal species. The aims of this study were to determine the efficacy of three classes of antiemetic drugs in a novel low dose cisplatin model of nausea and vomiting and measure change in potential nausea biomarkers arginine vasopressin (AVP) and cortisol. A four period cross-over blinded study was conducted in eight healthy beagle dogs of both genders. Dogs were administered 18 mg/m2 cisplatin intravenously, followed 45 min later by a 15 min infusion of either placebo (saline) or antiemetic treatment with ondansetron (0.5 mg/kg; 5-HT3 antagonist), maropitant (1 mg/kg; NK1 antagonist) or metoclopramide (0.5 mg/kg; D2 antagonist). The number of vomits and nausea associated behaviours, scored on a visual analogue scale, were recorded every 15 min for 8 h following cisplatin administration. Plasma samples were collected to measure AVP, cortisol and antiemetic drug concentrations

Impaired Cardiac and Skeletal Muscle Energetics Following Anthracycline Therapy for Breast Cancer

Acknowledgments The fellow (Dr Gamble) recruited participants, scheduled, coordinated, and performed all clinical imaging investigations, patients skeletal muscle biopsies and venesection, conducted mitochondrial copy number analysis of muscle biopsies under supervision, analyzed all data, performed statistical analyses under supervision, and drafted this article. H. Khan and A. Rudd helped with the investigations and reviewed and contributed to this article. S. Baliga provided the healthy volunteer skeletal muscle biopsies. Dr Ross designed and developed the protocol for cardiac and skeletal muscle spectroscopy. L. Cheyne supervised muscle biopsy analyses. Drs Unger and Linke performed the skeletal muscle transmission electron microscopy and immunofluorescence confocal microscopy investigations. Dr Horgan is the study statistician. Drs Urquhart, Masannat, Elsberger, Fuller, Mustafa, and Sharma identified and recruited participants and reviewed and contributed to this article. Drs Hannah, Sharma, and Saunders contributed to the design of the study. D. Dawson (PI) designed the study, obtained funding (together with Drs Sharma and Masannat) and regulatory approvals, supervised the unfolding of the study, its analyses and revised the article drafts. Sources of Funding Tenovus Scotland G18.01, D. Dawson and Dr Sharma, Friends of Anchor 2019, Grampian National Health Service-Endowments (Drs Sharma and Masannat), British Health Foundation PG/18/35/33786 to D. Dawson funded DG salary and BHF FS/RTF/20/30009 to D. Dawson funded AR salary.Peer reviewedPublisher PD

Workshop on accounting for fishers and other stakeholders’ perceptions of the dynamics of fish stocks in ICES advice (WKAFPA)

The objective of the Workshop on accounting for fishers and other stakeholders’ perceptions of the dynamics of fish stocks in ICES advice (WKAFPA) was to identify where and how stake- holder information could be incorporated in the ICES fisheries advice process. It adopted an operational definition of the concept of perception, where perceptions result from observations, interpreted in light of experience, that can be supported by data, information and knowledge to generate evidence about them. Stakeholder information can be either structured (e.g. routinely collected information in a standardized format) or unstructured (e.g. experiential information) and either of those can inform decisions made during the production of ICES advice. Most notably, the group identified there was a need to engage with stakeholders earlier in the process, i.e. before benchmarks meetings take place and before preliminary assessment results are used as the basis to predict total allowable catches for upcoming advice (Figure 4.2). It was therefore recommended to include in the ICES process the organisation of pre-bench- mark/roadmap workshops where science and data needs of upcoming benchmarks can be iden- tified, followed by making arrangements how scientists and stakeholders can collaborate to ac- cess, prepare for use (where relevant) and document the structured and unstructured infor- mation well ahead of the benchmark meetings. It was also recommended to organise ‘sense-checking’ sessions with stakeholders when prelim- inary assessments are available but not yet used as the basis for advisory production. This would allow stakeholders and assessment scientists to verify available knowledge and data against stock perceptions and provide additional considerations relevant for the production of TAC ad- vice. Next to these two additional activities, it is recommended that communication on differ- ences in stakeholder perception or data derived perceptions are communicated within the ICES assessment reports as well as in the ICES advice in a transparent manner. Not only should dif- ferences or similarities be documented and communicated, in those cases where there are differ- ences in perception between ICES stock assessments and stakeholders, a working group, external to the assessment working groups, should evaluate these differences and describe whether these differences can be logically explained or require further investigation. This outcome of this pro- cess may potentially lead to new data collection or additional analyses suitable for input to benchmarks. Essential in this entire process is making sure the same language is spoken between scientists and stakeholders, that there are clear and transparent processes in place on how to deal with stakeholder information and communicate clearly how this information is used in the prepara- tion of ICES advice.info:eu-repo/semantics/publishedVersio

Introduction: Shakespeare's public spheres

Habermas’ sense of a “cultural Public Sphere” is a notoriously complex term and, when applied to Early Modern cultures, needs careful definition. This essay both introduces the variety of methods by which we might approach playtexts with a view to their public – auditory – impact and contributes to a debate about an audience's understanding of Shakespeare's plays. By selecting two words and their spread of use in one play, Twelfth Night, we might appreciate the potential for meaningful ambiguity latent in how we hear the language of live performance. If we search for how certain terms (in this case, the cluster of semes derived from repetitions of “fancy” and “play”), we might find at times incompatible senses, yet we get near to appreciating the range of Early Modern dramatic language

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Workshop on accounting for fishers and other stakeholders’ perceptions of the dynamics of fish stocks in ICES advice (WKAFPA)

The objective of the Workshop on accounting for fishers and other stakeholders’ perceptions of the dynamics of fish stocks in ICES advice (WKAFPA) was to identify where and how stakeholder information could be incorporated in the ICES fisheries advice process. It adopted an operational definition of the concept of perception, where perceptions result from observations, interpreted in light of experience, that can be supported by data, information and knowledge to generate evidence about them. Stakeholder information can be either structured (e.g. routinely collected information in a standardized format) or unstructured (e.g. experiential information) and either of those can inform decisions made during the production of ICES advice. Most notably, the group identified there was a need to engage with stakeholders earlier in the process, i.e. before benchmarks meetings take place and before preliminary assessment results are used as the basis to predict total allowable catches for upcoming advice (Figure 4.2). It was therefore recommended to include in the ICES process the organisation of pre-benchmark/roadmap workshops where science and data needs of upcoming benchmarks can be identified, followed by making arrangements how scientists and stakeholders can collaborate to access, prepare for use (where relevant) and document the structured and unstructured information well ahead of the benchmark meetings. It was also recommended to organise ‘sense-checking’ sessions with stakeholders when preliminary assessments are available but not yet used as the basis for advisory production. This would allow stakeholders and assessment scientists to verify available knowledge and data against stock perceptions and provide additional considerations relevant for the production of TAC advice. Next to these two additional activities, it is recommended that communication on differences in stakeholder perception or data derived perceptions are communicated within the ICES assessment reports as well as in the ICES advice in a transparent manner. Not only should differences or similarities be documented and communicated, in those cases where there are differences in perception between ICES stock assessments and stakeholders, a working group, external to the assessment working groups, should evaluate these differences and describe whether these differences can be logically explained or require further investigation. This outcome of this process may potentially lead to new data collection or additional analyses suitable for input to benchmarks. Essential in this entire process is making sure the same language is spoken between scientists and stakeholders, that there are clear and transparent processes in place on how to deal with stakeholder information and communicate clearly how this information is used in the preparation of ICES advice.Peer reviewe

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2):a multicentre observational cohort study

Background: Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Methods: Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Findings: Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively). Interpretation: In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation. Funding: The Stroke Association and the British Heart Foundation

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention