An adaptive paradigm for detecting the individual duration of the preparatory period in the choice reaction time task

According to the sequential stage model, the selection and the execution of a motor response are two distinct independent processes. Here, we propose a new adaptive paradigm for identifying the individual duration of the response preparatory period based on the motor reaction time (RT) data. The results are compared using the paradigm with constant values of the preparatory period. Two groups of participants performed on either an easy (Group 1) or a hard (Group 2) response selection task with two types of stimuli based on the preparatory period parameters: (1) stimuli with a constant preparatory period duration of 0 or 1200 ms and (2) stimuli with adaptive preparatory period durations. Our analysis showed an increase in the duration of the response selection process as a function of increasing task complexity when using both paradigms with constant and adaptive values of the preparatory period duration. We conclude that the adaptive paradigm proposed in the current paper has several important advantages over the constant paradigm in terms of measuring the response accuracy while being equally efficiently in capturing other critical response parameters

Ethnicity and COVID-19 cardiovascular complications: a multi-center UK cohort

BACKGROUND: Recent reports suggest an association between ethnicity and COVID-19 mortality. In the present multi-center study, we aimed to assess the differences underlying this association, and ascertain whether ethnicity also mediates other aspects of COVID-19 like cardiovascular complications. METHODS: Data were collected from a mixed-ethnicity UK cohort of 613 patients admitted and diagnosed COVID-19 positive, across six hospitals in London during the second half of March 2020: 292 were White Caucasian ethnicity, 203 were Asian and 118 were of Afro-Caribbean ethnicity. RESULTS: Caucasian patients were older (P<0.001) and less likely to have hypertension (P=0.038), while Afro-Caribbean patients had higher prevalence of diabetes mellitus (P<0.001). Asian patients were more likely to present with venous thromboembolic disease (adj.OR=4.10, 95% CI 1.49-11.27, P=0.006). On the other hand, Afro-Caribbean had more heart failure (adj.OR=3.64, 95% CI 1.50-8.84, P=0.004) and myocardial injury (adj.OR=2.64, 95% CI 1.10-6.35, P=0.030). Importantly, our adjusted multi-variate Cox regression analysis revealed significantly higher all-cause mortality both for Asian (adj.HR=1.89, 95% CI 1.23-2.91, P=0.004) and Afro-Caribbean ethnicity (adj.HR=2.09, 95% CI 1.30-3.37, P=0.002). CONCLUSIONS: Our data show that COVID-19 may have different presentations and follow different clinical trajectories depending on the ethnicity of the affected subject. Awareness of complications more likely to arise in specific ethnicities will allow a more timely diagnosis and preventive measures for patients at risk. Due to increased mortality, individuals of Afro-Caribbean and Asian ethnicity should be considered as high-risk groups. This may have an impact on health-resource allocation and planning, definition of vulnerable groups, disease management, and the protection of healthcare workers at the frontline

High sensitivity troponin and COVID-19 outcomes

Background: Recent reports have demonstrated high troponin levels in patients affected with COVID-19. In the present study, we aimed to determine the association between admission and peak troponin levels and COVID-19 outcomes. / Methods: This was an observational multi-ethnic multi-centre study in a UK cohort of 434 patients admitted and diagnosed COVID-19 positive, across six hospitals in London, UK during the second half of March 2020. / Results: Myocardial injury, defined as positive troponin during admission was observed in 288 (66.4%) patients. Age (OR: 1.68 [1.49–1.88], p <.001), hypertension (OR: 1.81 [1.10–2.99], p =.020) and moderate chronic kidney disease (OR: 9.12 [95% CI: 4.24–19.64], p <.001) independently predicted myocardial injury. After adjustment, patients with positive peak troponin were more likely to need non-invasive and mechanical ventilation (OR: 2.40 [95% CI: 1.27–4.56], p =.007, and OR: 6.81 [95% CI: 3.40–13.62], p <.001, respectively) and urgent renal replacement therapy (OR: 4.14 [95% CI: 1.34–12.78], p =.013). With regards to events, and after adjustment, positive peak troponin levels were independently associated with acute kidney injury (OR: 6.76 [95% CI: 3.40–13.47], p <.001), venous thromboembolism (OR: 11.99 [95% CI: 3.20–44.88], p <.001), development of atrial fibrillation (OR: 10.66 [95% CI: 1.33–85.32], p =.026) and death during admission (OR: 2.40 [95% CI: 1.34–4.29], p =.003). Similar associations were observed for admission troponin. In addition, median length of stay in days was shorter for patients with negative troponin levels: 8 (5–13) negative, 14 (7–23) low-positive levels and 16 (10–23) high-positive (p <.001). / Conclusions: Admission and peak troponin appear to be predictors for cardiovascular and non-cardiovascular events and outcomes in COVID-19 patients, and their utilisation may have an impact on patient management

Ethical climate and intention to leave among critical care clinicians : an observational study in 68 intensive care units across Europe and the United States

PurposeApart from organizational issues, quality of inter-professional collaboration during ethical decision-making may affect the intention to leave one's job. To determine whether ethical climate is associated with the intention to leave after adjustment for country, ICU and clinicians characteristics.MethodsPerceptions of the ethical climate among clinicians working in 68 adult ICUs in 12 European countries and the US were measured using a self-assessment questionnaire, together with job characteristics and intent to leave as a sub-analysis of the Dispropricus study. The validated ethical decision-making climate questionnaire included seven factors: not avoiding decision-making at end-of-life (EOL), mutual respect within the interdisciplinary team, open interdisciplinary reflection, ethical awareness, self-reflective physician leadership, active decision-making at end-of-life by physicians, and involvement of nurses in EOL. Hierarchical mixed effect models were used to assess associations between these factors, and the intent to leave in clinicians within ICUs, within the different countries.ResultsOf 3610 nurses and 1137 physicians providing ICU bedside care, 63.1% and 62.9% participated, respectively. Of 2992 participating clinicians, 782 (26.1%) had intent to leave, of which 27% nurses, 24% junior and 22.7% senior physicians. After adjustment for country, ICU and clinicians characteristics, mutual respect OR 0.77 (95% CI 0.66- 0.90), open interdisciplinary reflection (OR 0.73 [95% CI 0.62-0.86]) and not avoiding EOL decisions (OR 0.87 [95% CI 0.77-0.98]) were all associated with a lower intent to leave.ConclusionThis is the first large multicenter study showing an independent association between clinicians' intent to leave and the quality of the ethical climate in the ICU. Interventions to reduce intent to leave may be most effective when they focus on improving mutual respect, interdisciplinary reflection and active decision-making at EOL

Outcome in patients perceived as receiving excessive care across different ethical climates: a prospective study in 68 intensive care units in Europe and the USA

Purpose: Whether the quality of the ethical climate in the intensive care unit (ICU) improves the identification of patients receiving excessive care and affects patient outcomes is unknown. Methods: In this prospective observational study, perceptions of excessive care (PECs) by clinicians working in 68 ICUs in Europe and the USA were collected daily during a 28-day period. The quality of the ethical climate in the ICUs was assessed via a validated questionnaire. We compared the combined endpoint (death, not at home or poor quality of life at 1 year) of patients with PECs and the time from PECs until written treatment-limitation decisions (TLDs) and death across the four climates defined via cluster analysis. Results: Of the 4747 eligible clinicians, 2992 (63%) evaluated the ethical climate in their ICU. Of the 321 and 623 patients not admitted for monitoring only in ICUs with a good (n = 12, 18%) and poor (n = 24, 35%) climate, 36 (11%) and 74 (12%), respectively were identified with PECs by at least two clinicians. Of the 35 and 71 identified patients with an available combined endpoint, 100% (95% CI 90.0–1.00) and 85.9% (75.4–92.0) (P = 0.02) attained that endpoint. The risk of death (HR 1.88, 95% CI 1.20–2.92) or receiving a written TLD (HR 2.32, CI 1.11–4.85) in patients with PECs by at least two clinicians was higher in ICUs with a good climate than in those with a poor one. The differences between ICUs with an average climate, with (n = 12, 18%) or without (n = 20, 29%) nursing involvement at the end of life, and ICUs with a poor climate were less obvious but still in favour of the former. Conclusion: Enhancing the quality of the ethical climate in the ICU may improve both the identification of patients receiving excessive care and the decision-making process at the end of life

Ethical climate and intention to leave among critical care clinicians: an observational study in 68 intensive care units across Europe and the United States

Purpose: Apart from organizational issues, quality of inter-professional collaboration during ethical decision-making may affect the intention to leave one’s job. To determine whether ethical climate is associated with the intention to leave after adjustment for country, ICU and clinicians characteristics. Methods: Perceptions of the ethical climate among clinicians working in 68 adult ICUs in 12 European countries and the US were measured using a self-assessment questionnaire, together with job characteristics and intent to leave as a sub-analysis of the Dispropricus study. The validated ethical decision-making climate questionnaire included seven factors: not avoiding decision-making at end-of-life (EOL), mutual respect within the interdisciplinary team, open interdisciplinary reflection, ethical awareness, self-reflective physician leadership, active decision-making at end-of-life by physicians, and involvement of nurses in EOL. Hierarchical mixed effect models were used to assess associations between these factors, and the intent to leave in clinicians within I

Gene-Expression Profiling Suggests Impaired Signaling via the Interferon Pathway in Cstb(-/-) Microglia

Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1, OMIM254800) is an autosomal recessive neurodegenerative disorder characterized by stimulus-sensitive and action-activated myoclonus, tonic-clonic epileptic seizures, and ataxia. Loss-of-function mutations in the gene encoding the cysteine protease inhibitor cystatin B (CSTB) underlie EPM1. The deficiency of CSTB in mice (Cstb(-/-) mice) generates a phenotype resembling the symptoms of EPM1 patients and is accompanied by microglial activation at two weeks of age and an upregulation of immune system-associated genes in the cerebellum at one month of age. To shed light on molecular pathways and processes linked to CSTB deficiency in microglia we characterized the transcriptome of cultured Cstb(-/-) mouse microglia using microarray hybridization and RNA sequencing (RNA-seq). The gene expression profiles obtained with these two techniques were in good accordance and not polarized to either pro- or anti-inflammatory status. In Cstb(-/-) microglia, altogether 184 genes were differentially expressed. Of these, 33 genes were identified by both methods. Several interferon-regulated genes were weaker expressed in Cstb(-/-) microglia compared to control. This was confirmed by quantitative real-time PCR of the transcripts Irf7 and Stat1. Subsequently, we explored the biological context of CSTB deficiency in microglia more deeply by functional enrichment and canonical pathway analysis. This uncovered a potential role for CSTB in chemotaxis, antigen-presentation, and in immune-and defense response-associated processes by altering JAK-STAT pathway signaling. These data support and expand the previously suggested involvement of inflammatory processes to the disease pathogenesis of EPM1 and connect CSTB deficiency in microglia to altered expression of interferon-regulated genes.Peer reviewe

Antimicrobial and Antioxidant Potential of Scenedesmus obliquus Microalgae in the Context of Integral Biorefinery Concept

Small-scale photobioreactors (PBRs) in the inoculum stage were designed with internal (red or green) and external white LED light as an initial step of a larger-scale installation aimed at fulfilling the integral biorefinery concept for maximum utilization of microalgal biomass in a multifunctional laboratory. The specific growth rate of Scenedesmus obliquus (Turpin) K&uuml;tzing biomass for given cultural conditions was analyzed by using MAPLE software. For the determination of total polyphenols, flavonoids, chlorophyll &ldquo;a&rdquo; and &ldquo;b&rdquo;, carotenoids and lipids, UHPLC-HRMS, ISO-20776/1, ISO-10993-5 and CUPRAC tests were carried out. Under red light growing, a higher content of polyphenols was found, while the green light favoured the flavonoid accumulation in the biomass. Chlorophylls, carotenoids and lipids were in the same order of magnitude in both samples. The dichloromethane extracts obtained from the biomass of each PBR synergistically potentiated at low concentrations (0.01&ndash;0.05 mg/mL) the antibacterial activity of penicillin, fluoroquinolones or oregano essential oil against the selected food-borne pathogens (Staphylococcus aureus, Escherichia coli and Salmonella typhimurium) without showing any in vitro cytotoxicity. Both extracts exhibited good cupric ion-reducing antioxidant capacity at concentrations above 0.042&ndash;0.08 mg/mL. The UHPLC-HRMS analysis revealed that both extracts contained long chain fatty acids and carotenoids thus explaining their antibacterial and antioxidant potential. The applied engineering approach showed a great potential to modify microalgae metabolism for the synthesis of target compounds by S. obliquus with capacity for the development of health-promoting nutraceuticals for poultry farming