European Association of Cardiothoracic Anesthesiology and Intensive Care (EACTAIC) Fellowship Curriculum: Second Edition

This document represents the first update of the Cardiothoracic and Vascular Anaesthesia Fellowship Curriculum of the European Association of Cardiothoracic Anaesthesiology and Intensive Care. After obtaining feedback from exit interviews with fellows in training, graduate fellows, and program directors, 2 modified online Delphi procedures with questionnaires were conducted. A consensus was reached when two-thirds of responding committee members gave green or yellow ratings on a traffic light system, and >70% indicated strong agreement or agreement on a 5-point Likert scale. The new regulations include the following: (1) more flexibility in the fellows` rotation, as long as the total number of days, rotations, and cases are completed during the training year; (2) recommendation for strict compliance with national working-time guidelines; (3) no extension of fellowship training to compensate for annual and/or sick leave, unless the required minimum number of cases and rotations are not reached; (4) interruption of fellowship training for >12 months is allowed for personal or medical reasons; (5) introduction of a checklist for quantitative assessment of standard clinical skills; (6) recommendations for a uniform structure of exit interviews; (7) possibility of a 1-month training rotation in a postanesthesia care unit instead of an intensive care unit; and (8) provided all other requirements have been met, the allowance of progression from the basic training year to the advanced fellowship training year without first passing the transesophageal echocardiography examination

Mining predicted crystal structure landscapes with high throughput crystallisation: old molecules, new insights

Organic molecules tend to close pack to form dense structures when they are crystallized from organic solvents. Porous molecular crystals defy this rule: they typically crystallize with lattice solvent in the interconnected pores. However, the design and discovery of such structures is often challenging and time consuming, in part because it is difficult to predict solvent effects on crystallization. Here, we combine crystal structure prediction (CSP) with a high-throughput crystallization screening method to accelerate the discovery of stable hydrogen-bonded frameworks. We exemplify this strategy by finding new phases of two well-studied molecules in a computationally targeted way. Specifically, we find a new porous polymorph of trimesic acid, δ-TMA, that has a guest free hexagonal pore structure, as well as three new solvent-stabilized diamondoid frameworks of adamantane-1,3,5,7-tetracarboxylic acid (ADTA)

Clinical, biochemical and genetic spectrum of 70 patients with ACAD9 deficiency: Is riboflavin supplementation effective?

Background: Mitochondrial acyl-CoA dehydrogenase family member 9 (ACAD9) is essential for the assembly of mitochondrial respiratory chain complex I. Disease causing biallelic variants in ACAD9 have been reported in individuals presenting with lactic acidosis and cardiomyopathy. Results: We describe the genetic, clinical and biochemical findings in a cohort of 70 patients, of whom 29 previously unpublished. We found 34 known and 18 previously unreported variants in ACAD9. No patients harbored biallelic loss of function mutations, indicating that this combination is unlikely to be compatible with life. Causal pathogenic variants were distributed throughout the entire gene, and there was no obvious genotype-phenotype correlation. Most of the patients presented in the first year of life. For this subgroup the survival was poor (50% not surviving the first 2 years) comparing to patients with a later presentation (more than 90% surviving 10 years). The most common clinical findings were cardiomyopathy (85%), muscular weakness (75%) and exercise intolerance (72%). Interestingly, severe intellectual deficits were only reported in one patient and

A knowledge creation framework for academia toward agroecological transformations of food systems

Industrialized agriculture, characterized by high inputs, large-scale monocultures, and confined livestock production, with a narrow focus on profit, is a major transgressor of societal and planetary boundaries. It fuels climate change, biodiversity loss, water and soil degradation, nutritional deficiencies, public health issues, cultural erosion, and socioeconomic inequalities. As early-career researchers in agricultural sciences, we are concerned about these systemic crises and recognize that participating in normative academic practices without reflection may reinforce the prevailing industrialized food system. Motivated by the dissonance between the potential impact of our work and our vision of a better future, in this paper we describe and challenge academic praxis in agricultural sciences to tackle the interconnected crises. We do this by developing a framework of two drivers of academic knowledge production, power and values, and two mechanisms, motives and relationality. We argue that in the current dominant food system, power is consolidated and hierarchical, driven by the values of growthism and reductionism, motivated by efficiency and productivism, and characterized by extractive and anthropocentric relationality. Furthermore, we highlight evidence of the negative outcomes associated with this system, including the challenges we face and may potentially contribute to as participants. We then envision transformed food systems through examples of counter-hegemonic knowledge production systems, grounded in agroecological principles, in which power is distributed and horizontal, the primary values are solidarity and holism, motives enhance sufficiency and sovereignty, and relationality is reciprocal and based on care. By examining the current system and offering examples of alternatives, we aim to help distinguish between research that upholds the statu-quo and research that fosters change. We aim to inspire ourselves and others to reconnect with our agency and contribute towards transformed knowledge systems where food systems, underpinned by the values of agroecology, are more capable of sustaining life on this planet in an equitable and just manner

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Report on the sixth blind test of organic crystal-structure prediction methods

The sixth blind test of organic crystal-structure prediction (CSP) methods has been held, with five target systems: a small nearly rigid molecule, a polymorphic former drug candidate, a chloride salt hydrate, a co-crystal, and a bulky flexible molecule. This blind test has seen substantial growth in the number of submissions, with the broad range of prediction methods giving a unique insight into the state of the art in the field. Significant progress has been seen in treating flexible molecules, usage of hierarchical approaches to ranking structures, the application of density-functional approximations, and the establishment of new workflows and "best practices" for performing CSP calculations. All of the targets, apart from a single potentially disordered Z` = 2 polymorph of the drug candidate, were predicted by at least one submission. Despite many remaining challenges, it is clear that CSP methods are becoming more applicable to a wider range of real systems, including salts, hydrates and larger flexible molecules. The results also highlight the potential for CSP calculations to complement and augment experimental studies of organic solid forms

Induction of cancer neoantigens facilitates development of clinically relevant models for the study of pancreatic cancer immunobiology

Neoantigen burden and CD8 T cell infiltrate are associated with clinical outcome in pancreatic ductal adenocarcinoma (PDAC). A shortcoming of many genetic models of PDAC is the lack of neoantigen burden and limited T cell infiltrate. The goal of the present study was to develop clinically relevant models of PDAC by inducing cancer neoantigens in KP2, a cell line derived from the KPC model of PDAC. KP2 was treated with oxaliplatin and olaparib (OXPARPi), and a resistant cell line was subsequently cloned to generate multiple genetically distinct cell lines (KP2-OXPARPi clones). Clones A and E are sensitive to immune checkpoint inhibition (ICI), exhibit relatively high T cell infiltration, and have significant upregulation of genes involved in antigen presentation, T cell differentiation, and chemokine signaling pathways. Clone B is resistant to ICI and is similar to the parental KP2 cell line in terms of relatively low T cell infiltration and no upregulation of genes involved in the pathways noted above. Tumor/normal exome sequencing and in silico neoantigen prediction confirms successful generation of cancer neoantigens in the KP2-OXPARPi clones and the relative lack of cancer neoantigens in the parental KP2 cell line. Neoantigen vaccine experiments demonstrate that a subset of candidate neoantigens are immunogenic and neoantigen synthetic long peptide vaccines can restrain Clone E tumor growth. Compared to existing models, the KP2-OXPARPi clones better capture the diverse immunobiology of human PDAC and may serve as models for future investigations in cancer immunotherapies and strategies targeting cancer neoantigens in PDAC

A recurrent mitochondrial p.Trp22Arg NDUFB3 variant causes a distinctive facial appearance, short stature and a mild biochemical and clinical phenotype

Background Isolated Complex I deficiency is the most common paediatric mitochondrial disease presentation, associated with poor prognosis and high mortality. Complex I comprises 44 structural subunits with at least 10 ancillary proteins; mutations in 29 of these have so far been associated with mitochondrial disease but there are limited genotype-phenotype correlations to guide clinicians to the correct genetic diagnosis. Methods Patients were analysed by whole-exome sequencing, targeted capture or candidate gene sequencing. Clinical phenotyping of affected individuals was performed. Results We identified a cohort of 10 patients from 8 families (7 families are of unrelated Irish ancestry) all of whom have short stature (C, p.Trp22Arg NDUFB3 variant. Two sibs presented with primary short stature without obvious metabolic dysfunction. Analysis of skeletal muscle from three patients confirmed a defect in Complex I assembly. Conclusions Our report highlights that the long-term prognosis related to the p.Trp22Arg NDUFB3 mutation can be good, even for some patients presenting in acute metabolic crisis with evidence of an isolated Complex I deficiency in muscle. Recognition of the distinctive facial features—particularly when associated with markers of mitochondrial dysfunction and/or Irish ancestry—should suggest screening for the p.Trp22Arg NDUFB3 mutation to establish a genetic diagnosis, circumventing the requirement of muscle biopsy to direct genetic investigations

The Political Economy of Productivity in Brazil

This paper explores the link between Brazil's political institutions and its disappointing productivity and growth in recent decades. Although political institutions provide the president with incentives and the instruments to pursue monetary stability and fiscal discipline they simultaneously raise the costs of achieving those very objectives. The insulation of certain expenditures from presidential discretion necessitates the use of other policy options, such as high taxation levels and cuts in unprotected expenditures, which put a drag on productivity and growth. In a context of robust checks and balances and interest group fragmentation, a state overburdened by constitutional entitlements has resorted to massive increases in taxation. The resulting environment possesses both essential elements for sustainable economic growth and distortions that conspire against its realization. While some improvements in productivity and growth have occurred in the past decade, the pace has been slow and incremental

European Association of Cardiothoracic Anesthesiology and Intensive Care Pediatric Cardiac Anesthesia Fellowship Curriculum:First Edition

International audiencePediatric cardiac anesthesia is a subspecialty of cardiac and pediatric anesthesiology dedicated to the perioperative care of patients with congenital heart disease. Members of the Congenital and Education Subcommittees of the European Association of Cardiothoracic Anaesthesiology and Intensive Care (EACTAIC) agreed on the necessity to develop an EACTAIC pediatric cardiac anesthesia fellowship curriculum. This manuscript represents a consensus on the composition and the design of the EACTAIC Pediatric Cardiac Anesthesia Fellowship program. This curriculum provides a basis for the training of future pediatric cardiac anesthesiologists by clearly defining the theoretical and practical requirements for fellows and host centers