Projects to be realized

Este texto explora "Proyectos a realizar", de Edgardo Antonio Vigo, como paradigmas de un arte conceptual participativo con raíces en la poesía y en el juego, y sus teorías como eslabones perdidos en la comprensión actual del conceptualismo en América del Sur y su conexión con la experimentación poética. Se considera estas obras tanto dentro del marco de la experimentación conceptual en la Argentina como en relación con las obras del artista George Brecht, miembro del grupo internacional Fluxus.This text explores "Projects to Be Realized" as paradigms of a participatory conceptual art with roots in poetry and game, and his theories as missing links in current understandings of conceptualism in South America and its connection to poetic experimentation. It considers these works both within the framework of conceptual art experimentation in Argentina and in relation to the works of artist George Brecht, member of the international Fluxus group.Facultad de Bellas Arte

Projects to be realized

Este texto explora "Proyectos a realizar", de Edgardo Antonio Vigo, como paradigmas de un arte conceptual participativo con raíces en la poesía y en el juego, y sus teorías como eslabones perdidos en la comprensión actual del conceptualismo en América del Sur y su conexión con la experimentación poética. Se considera estas obras tanto dentro del marco de la experimentación conceptual en la Argentina como en relación con las obras del artista George Brecht, miembro del grupo internacional Fluxus.This text explores "Projects to Be Realized" as paradigms of a participatory conceptual art with roots in poetry and game, and his theories as missing links in current understandings of conceptualism in South America and its connection to poetic experimentation. It considers these works both within the framework of conceptual art experimentation in Argentina and in relation to the works of artist George Brecht, member of the international Fluxus group.Facultad de Bellas Arte

Sectoral Impacts of Invasive Species in the United States and Approaches to Management

Invasive species have a major effect on many sectors of the U.S. economy and on the well-being of its citizens. Their presence impacts animal and human health, military readiness, urban vegetation and infrastructure, water, energy and transportations systems, and indigenous peoples in the United States (Table 9.1). They alter bio-physical systems and cultural practices and require significant public and private expenditure for control. This chapter provides examples of the impacts to human systems and explains mechanisms of invasive species’ establishment and spread within sectors of the U.S. economy. The chapter is not intended to be comprehensive but rather to provide insight into the range and severity of impacts. Examples provide context for ongoing Federal programs and initiatives and support State and private efforts to prevent the introduction and spread of invasive species and eradicate and control established invasive species

Life experiences throughout the ifespan: What do people say (or not) about them?

Life experiences have been a topic of interest for researchers and clinicians for decades. Current knowledge is rooted in two distinct approaches, i.e., personality psychology and psychosomatics. Whereas the first is interested in ordinary life stories of nonclinical individuals, based on a more qualitative, in-depth, and person-driven approach, psychosomatics stresses negative events, mainly in clinical samples, and presents a more quantitative, general, and construct-driven approach. Consequently, available evidence is dispersed and unrelated and many basic questions remain unanswered. This study aimed to explore occurrence, developmental stage, valence, and impact of life experiences and to analyze critical answering patterns (i.e., “I don’t remember,” missingness). Through a cross-sectional retrospective design, 394 adults from the community answered the Lifetime Experiences Scale, which covers 75 life experiences organized in eight domains (i.e., school, job, health, leisure, living conditions, adverse experiences, achievements, and people and relationships). Occurrence of life experiences varied greatly, and the mean number of experiences reported was approximately 30. Regarding developmental stage, most experiences were reported in just one stage—mainly adulthood—however, some could be considered chronic. Globally, life experiences tended to be clearly rated as positive or as negative; additionally, assessed experiences were mainly appraised as positive. Moreover, participants presented their experiences as significant, rating them as high impact. Overall, critical answering patterns were not very expressive: “I don’t remember” and missing answers were below 2 and 5%, respectively, in the majority of experiences. These findings offer several important new insights, suggesting that life experiences are mainly an idiosyncratic topic.This manuscript is part of a doctoral dissertation, which had the support of the Portuguese Foundation for Science and Technology (FCT), through the PhD grant with the reference SFRH/ BD/76022/2011, funded by POPH-QREN-Typology 4.1-Advanced Training, reimbursed by the European Social Fund and national funds from State Budget. This study was conducted at Psychology Research Centre (UID/PSI/01662/2013), University of Minho, and supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Education and Science through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653).info:eu-repo/semantics/publishedVersio

Developmental expression of COE across the Metazoa supports a conserved role in neuronal cell-type specification and mesodermal development

The transcription factor COE (collier/olfactory-1/early B cell factor) is an unusual basic helix–loop–helix transcription factor as it lacks a basic domain and is maintained as a single copy gene in the genomes of all currently analysed non-vertebrate Metazoan genomes. Given the unique features of the COE gene, its proposed ancestral role in the specification of chemosensory neurons and the wealth of functional data from vertebrates and Drosophila, the evolutionary history of the COE gene can be readily investigated. We have examined the ways in which COE expression has diversified among the Metazoa by analysing its expression from representatives of four disparate invertebrate phyla: Ctenophora (Mnemiopsis leidyi); Mollusca (Haliotis asinina); Annelida (Capitella teleta and Chaetopterus) and Echinodermata (Strongylocentrotus purpuratus). In addition, we have studied COE function with knockdown experiments in S. purpuratus, which indicate that COE is likely to be involved in repressing serotonergic cell fate in the apical ganglion of dipleurula larvae. These analyses suggest that COE has played an important role in the evolution of ectodermally derived tissues (likely primarily nervous tissues) and mesodermally derived tissues. Our results provide a broad evolutionary foundation from which further studies aimed at the functional characterisation and evolution of COE can be investigated

Adult mental health provision in England : a national survey of acute day units

Background Acute Day Units (ADUs) exist in some English NHS Trusts as an alternative to psychiatric inpatient admission. However, there is a lack of information about the number, configuration, and functioning of such units, and about the extent to which additional units might reduce admissions. This cross-sectional survey and cluster analysis of ADUs aimed to identify, categorise, and describe Acute Day Units (ADUs) in England. Methods English NHS Mental Health Trusts with ADUs were identified in a mapping exercise, and a questionnaire was distributed to ADU managers. Cluster analysis was used to identify distinct models of service, and descriptive statistics are given to summarise the results of the survey questions. Results Two types of service were identified by the cluster analysis: NHS (n = 27; and voluntary sector services (n = 18). Under a third of NHS Trusts have access to ADUs. NHS services typically have multi-disciplinary staff teams, operate during office hours, offer a range of interventions (medication, physical checks, psychological interventions, group sessions, peer support), and had a median treatment period of 30 days. Voluntary sector services had mostly non-clinically qualified staff, and typically offered supportive listening on a one-off, drop-in basis. Nearly all services aim to prevent or reduce inpatient admissions. Voluntary sector services had more involvement by service users and carers in management and running of the service than NHS services. Conclusions The majority of NHS Trusts do not provide ADUs, despite their potential to reduce inpatient admissions. Further research of ADUs is required to establish their effectiveness and acceptability to service users, carers, and staff

A Model Analysis of Arterial Oxygen Desaturation during Apnea in Preterm Infants

Rapid arterial O2 desaturation during apnea in the preterm infant has obvious clinical implications but to date no adequate explanation for why it exists. Understanding the factors influencing the rate of arterial O2 desaturation during apnea () is complicated by the non-linear O2 dissociation curve, falling pulmonary O2 uptake, and by the fact that O2 desaturation is biphasic, exhibiting a rapid phase (stage 1) followed by a slower phase when severe desaturation develops (stage 2). Using a mathematical model incorporating pulmonary uptake dynamics, we found that elevated metabolic O2 consumption accelerates throughout the entire desaturation process. By contrast, the remaining factors have a restricted temporal influence: low pre-apneic alveolar causes an early onset of desaturation, but thereafter has little impact; reduced lung volume, hemoglobin content or cardiac output, accelerates during stage 1, and finally, total blood O2 capacity (blood volume and hemoglobin content) alone determines during stage 2. Preterm infants with elevated metabolic rate, respiratory depression, low lung volume, impaired cardiac reserve, anemia, or hypovolemia, are at risk for rapid and profound apneic hypoxemia. Our insights provide a basic physiological framework that may guide clinical interpretation and design of interventions for preventing sudden apneic hypoxemia

Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis (New EPOC): long-term results of a multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: The interim analysis of the multicentre New EPOC trial in patients with resectable colorectal liver metastasis showed a significant reduction in progression-free survival in patients allocated to cetuximab plus chemotherapy compared with those given chemotherapy alone. The focus of the present analysis was to assess the effect on overall survival. METHODS: New EPOC was a multicentre, open-label, randomised, controlled, phase 3 trial. Adult patients (aged ≥18 years) with KRAS wild-type (codons 12, 13, and 61) resectable or suboptimally resectable colorectal liver metastases and a WHO performance status of 0-2 were randomly assigned (1:1) to receive chemotherapy with or without cetuximab before and after liver resection. Randomisation was done centrally with minimisation factors of surgical centre, poor prognosis cancer, and previous adjuvant treatment with oxaliplatin. Chemotherapy consisted of oxaliplatin 85 mg/m2 administered intravenously over 2 h, l-folinic acid (175 mg flat dose administered intravenously over 2 h) or d,l-folinic acid (350 mg flat dose administered intravenously over 2 h), and fluorouracil bolus 400 mg/m2 administered intravenously over 5 min, followed by a 46 h infusion of fluorouracil 2400 mg/m2 repeated every 2 weeks (regimen one), or oxaliplatin 130 mg/m2 administered intravenously over 2 h and oral capecitabine 1000 mg/m2 twice daily on days 1-14 repeated every 3 weeks (regimen two). Patients who had received adjuvant oxaliplatin could receive irinotecan 180 mg/m2 intravenously over 30 min with fluorouracil instead of oxaliplatin (regimen three). Cetuximab was given intravenously, 500 mg/m2 every 2 weeks with regimen one and three or a loading dose of 400 mg/m2 followed by a weekly infusion of 250 mg/m2 with regimen two. The primary endpoint of progression-free survival was published previously. Secondary endpoints were overall survival, preoperative response, pathological resection status, and safety. Trial recruitment was halted prematurely on the advice of the Trial Steering Committee on Nov 1, 2012. All analyses (except safety) were done on the intention-to-treat population. Safety analyses included all randomly assigned patients. This trial is registered with ISRCTN, number 22944367. FINDINGS: Between Feb 26, 2007, and Oct 12, 2012, 257 eligible patients were randomly assigned to chemotherapy with cetuximab (n=129) or without cetuximab (n=128). This analysis was carried out 5 years after the last patient was recruited, as defined in the protocol, at a median follow-up of 66·7 months (IQR 58·0-77·5). Median progression-free survival was 22·2 months (95% CI 18·3-26·8) in the chemotherapy alone group and 15·5 months (13·8-19·0) in the chemotherapy plus cetuximab group (hazard ratio [HR] 1·17, 95% CI 0·87-1·56; p=0·304). Median overall survival was 81·0 months (59·6 to not reached) in the chemotherapy alone group and 55·4 months (43·5-71·5) in the chemotherapy plus cetuximab group (HR 1·45, 1·02-2·05; p=0·036). There was no significant difference in the secondary outcomes of preoperative response or pathological resection status between groups. Five deaths might have been treatment-related (one in the chemotherapy alone group and four in the chemotherapy plus cetuximab group). The most common grade 3-4 adverse events reported were: neutrophil count decreased (26 [19%] of 134 in the chemotherapy alone group vs 21 [15%] of 137 in the chemotherapy plus cetuximab group), diarrhoea (13 [10%] vs 14 [10%]), skin rash (one [1%] vs 22 [16%]), thromboembolic events (ten [7%] vs 11 [8%]), lethargy (ten [7%] vs nine [7%]), oral mucositis (three [2%] vs 14 [10%]), vomiting (seven [5%] vs seven [5%]), peripheral neuropathy (eight [6%] vs five [4%]), and pain (six [4%] vs six [4%]). INTERPRETATION: Although the addition of cetuximab to chemotherapy improves the overall survival in some studies in patients with advanced, inoperable metastatic disease, its use in the perioperative setting in patients with operable disease confers a significant disadvantage in terms of overall survival. Cetuximab should not be used in this setting. FUNDING: Cancer Research UK

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice