Extending life for people with a terminal illness: a moral right and an expensive death? Exploring societal perspectives

BACKGROUND: Many publicly-funded health systems apply cost-benefit frameworks in response to the moral dilemma of how best to allocate scarce healthcare resources. However, implementation of recommendations based on costs and benefit calculations and subsequent challenges have led to ‘special cases’ with certain types of health benefits considered more valuable than others. Recent debate and research has focused on the relative value of life extensions for people with terminal illnesses. This research investigates societal perspectives in relation to this issue, in the UK. METHODS: Q methodology was used to elicit societal perspectives from a purposively selected sample of data-rich respondents. Participants ranked 49 statements of opinion (developed for this study), onto a grid, according to level of agreement. These ‘Q sorts’ were followed by brief interviews. Factor analysis was used to identify shared points of view (patterns of similarity between individuals’ Q sorts). RESULTS: Analysis produced a three factor solution. These rich, shared accounts can be broadly summarised as: i) ‘A population perspective – value for money, no special cases’, ii) ‘Life is precious – valuing life-extension and patient choice’, iii) ‘Valuing wider benefits and opportunity cost - the quality of life and death’. From the factor descriptions it is clear that the main philosophical positions that have long dominated debates on the just allocation of resources have a basis in public opinion. CONCLUSIONS: The existence of certain moral positions in the views of society does not ethically imply, and pragmatically cannot mean, that all are translated into policy. Our findings highlight normative tensions and the importance of critically engaging with these normative issues (in addition to the current focus on a procedural justice approach to health policy). Future research should focus on i) the extent to which these perspectives are supported in society, ii) how respondents' perspectives relate to specific resource allocation questions, and iii) the characteristics of respondents associated with each perspective

Role of Arginine 285 in the Active Site of Rhodotorula gracilis d-Amino Acid Oxidase A SITE-DIRECTED MUTAGENESIS STUDY

Abstract Arg285, one of the very few conserved residues in the active site of d-amino acid oxidases, has been mutated to lysine, glutamine, aspartate, and alanine in the enzyme from the yeast Rhodotorula gracilis (RgDAAO). The mutated proteins are all catalytically competent. Mutations of Arg285 result in an increase (≈300-fold) ofK m for the d-amino acid and in a large decrease (≈500-fold) of turnover number. Stopped-flow analysis shows that the decrease in turnover is paralleled by a similar decrease in the rate of flavin reduction (k 2), the latter still being the rate-limiting step of the reaction. In agreement with data from the protein crystal structure, loss of the guanidinium group of Arg285 in the mutated DAAOs drastically reduces the binding of several carboxylic acids (e.g. benzoate). These results highlight the importance of this active site residue in the precise substrate orientation, a main factor in this redox reaction. Furthermore, Arg285 DAAO mutants have spectral properties similar to those of the wild-type enzyme, but show a low degree of stabilization of the flavin semiquinone and a change in the redox properties of the free enzyme. From this, we can unexpectedly conclude that Arg285 in the free enzyme form is involved in the stabilization of the negative charge on the N(1)-C(2)=O locus of the isoalloxazine ring of the flavin. We also suggest that the residue undergoes a conformational change in order to bind the carboxylate portion of the substrate/ligand in the complexed enzyme

ENCONTRANDO “PISTAS”: Um percurso etnográfico multissensorial sobreposto pelo desenho, fotografia e vídeo

This is an article that investigates Farroupilha Park, located in Porto Alegre (Rio Grande do Sul), through multi-sensory ways. Based on the idea of "clues", we analyze how drawing, images, colors, sounds and strokes can help us with the ethnographic enterprise. The research involved methodical procedures based on drawing, participant observation, and audiovisual recording. Theoretical analyses followed the principles and tools of urban and visual anthropologies. This text is the result of a meeting of three researchers during the month of January 2023 and, to reconcile our presence in the field, we propose a "flow" writing, where multiple narrator voices condense perceptions of continuity and rupture about the same experience.Trata-se de um artigo que investiga conhecer em formas multissensoriais o Parque Farroupilha, localizado em Porto Alegre (Rio Grande do Sul). A partir da ideia de“pistas”, analisamos como o desenho, as imagens, as cores, os sons e os traços podem nos ajudar com o empreendimento etnográfico. Para realizar esta pesquisa, foram utilizados procedimentos metodológicos baseados em desenho, observação participante e registro audiovisual. As análises teóricas seguiram os princípios e ferramentas das antropologias urbana e visual. Este texto é fruto de um encontro de três pesquisadoras durante o mês de janeiro de 2023 e, para conciliar a nossa presença em campo, propomos uma escrita em “fluxo”, onde múltiplas vozes narradoras condensam percepções de continuidade e ruptura acerca de uma mesma experiência

Understanding repolarization in the intracardiac unipolar electrogram: A long-lasting controversy revisited

Background: The optimal way to determine repolarization time (RT) from the intracardiac unipolar electrogram (UEG) has been a topic of debate for decades. RT is typically determined by either the Wyatt method or the “alternative method,” which both consider UEG T-wave slope, but differently.Objective: To determine the optimal method to measure RT on the UEG.Methods: Seven pig hearts surrounded by an epicardial sock with 100 electrodes were Langendorff-perfused with selective cannulation of the left anterior descending (LAD) coronary artery and submersed in a torso-shaped tank containing 256 electrodes on the torso surface. Repolarization was prolonged in the non-LAD-regions by infusing dofetilide and shortened in the LAD-region using pinacidil. RT was determined by the Wyatt (tWyatt) and alternative (tAlt) methods, in both invasive (recorded with epicardial electrodes) and in non-invasive UEGs (reconstructed with electrocardiographic imaging). tWyatt and tAlt were compared to local effective refractory period (ERP).Results: With contact mapping, mean absolute error (MAE) of tWyatt and tAlt vs. ERP were 21 ms and 71 ms, respectively. Positive T-waves typically had an earlier ERP than negative T-waves, in line with theory. tWyatt -but not tAlt-shortened by local infusion of pinacidil. Similar results were found for the non-invasive UEGs (MAE of tWyatt and tAlt vs. ERP were 30 ms and 92 ms, respectively).Conclusion: The Wyatt method is the most accurate to determine RT from (non) invasive UEGs, based on novel and historical analyses. Using it to determine RT could unify and facilitate repolarization assessment and amplify its role in cardiac electrophysiology

Prevalence of Seasonal Influenza Vaccination in Chronic Obstructive Pulmonary Disease (COPD) Patients in the Balearic Islands (Spain) and Its Effect on COPD Exacerbations: A Population-Based Retrospective Cohort Study

To determine the prevalence of influenza vaccination in chronic obstructive pulmonary disease (COPD) patients and its effect on COPD exacerbations, we conducted a retrospective population-based cohort study analyzing real-life data. We included all registered COPD patients ?40 years old using respiratory medication during the study period (2012?2013). Influenza vaccination during the 2012/2013 campaign was the parameter studied. Moderate and severe exacerbations during 2013 were the dependent outcome variables. Logistic regression adjusting for age, gender, concomitant asthma diagnosis, COPD severity, smoking status, number of moderate and severe exacerbations the previous year, and comorbidities was performed, and 59.6% of the patients received seasonal influenza vaccination. The percentage of patients with exacerbations was higher among those vaccinated. Influenza vaccination had a statistically significantly negative (non-protective) crude effect favoring the risk of severe exacerbations: OR: 1.20 (95% CI; 1.05?1.37). This association diminished and lost statistical significance after adjustment: aOR: 0.93 (95% CI; 0.74?1.18). The protective effect in the analysis restricted to the epidemic period was not significant: aOR: 0.82 (95% CI; 0.58?1.16). We concluded that prevalence of influenza vaccination was suboptimal. In contrast with most of the available evidence, our results did not support a protective effect of influenza vaccination on the risk of admission for COPD exacerbation

The association between preoperative body composition and aerobic fitness in patients scheduled for colorectal surgery

AIM: Although cardiopulmonary exercise testing (CPET) is considered the gold standard, a preoperative abdominal CT scan might also provide information concerning preoperative aerobic fitness for risk assessment. This study aimed to investigate the association between preoperative CT‐scan‐derived body composition variables and preoperative CPET variables of aerobic fitness in colorectal surgery. METHOD: In this retrospective cohort study, CT images at level L3 were analysed for skeletal muscle mass, skeletal muscle radiation attenuation, visceral adipose tissue (VAT) mass and subcutaneous adipose tissue mass. Regression analyses were performed to investigate the relation between CT‐scan‐derived body composition variables, CPET‐derived aerobic fitness and other preoperative patient‐related variables. Logistic regression analysis was performed to predict a preoperative anaerobic threshold (AT) ≤ 11.1 ml/kg/min as cut‐off for having a high risk for postoperative complications. RESULTS: Data from 78 patients (45 men; mean [SD] age 74.5 [6.4 years]) were analysed. A correlation coefficient of 0.55 was observed between absolute AT and skeletal muscle mass index. Absolute AT (R (2) of 51.1%) was lower in patients with a lower skeletal muscle mass index, together with higher age, lower body mass and higher American Society of Anesthesiologists (ASA) score. Higher ASA score (odds ratio 5.64; P = 0.033) and higher VAT mass (odds ratio 1.02; P = 0.036) were associated with an increased risk of an AT ≤ 11.1 ml/kg/min. CONCLUSION: Body composition variables from the preoperative CT scan were moderately associated with preoperative CPET‐derived aerobic fitness. Higher ASA score and higher VAT mass were associated with an increased risk of an AT ≤ 11.1 ml/kg/min

In situ modification of nanostructure configuration through the manipulation of hydrogen bonded amphiphile self-association

Herein, we report the synthesis of a novel amphiphilic salt containing a number of hydrogen bond donating (HBD) and accepting (HBA) functionalities. This amphiphile has been shown to self-associate via hydrogen bond formation in a DMSO solution, confirmed through a combination of NMR, UV-Vis and dynamic light scattering and supported by X-ray diffraction studies. The combination of different HBD and HBA functionalities within the amphiphile structure gives rise to a variety of competitive, self-associative hydrogen bonding modes that result in the formation of ‘frustrated’ hydrogen bonded nanostructures. These nanostructures can be altered through the addition of competitive HBD arrays and/or HBA anionic guests. The addition of these competitive species modifies the type of self-associative hydrogen bonding modes present between the amphiphilic molecules, triggering the in situ formation of novel hydrogen bonded nanostructures

Benefits and harm of systemic steroids for short- and long-term use in rhinitis and rhinosinusitis : an EAACI position paper

Correction: Volume: 10 Issue: 1 Article Number: 38 DOI: 10.1186/s13601-020-00343-w Published: SEP 28 2020Because of the inflammatory mechanisms of most chronic upper airway diseases such as rhinitis and chronic rhinosinusitis, systemic steroids have been used for their treatment for decades. However, it has been very well documented that-potentially severe-side-effects can occur with the accumulation of systemic steroid courses over the years. A consensus document summarizing the benefits of systemic steroids for each upper airway disease type, as well as highlighting the potential harms of this treatment is currently lacking. Therefore, a panel of international experts in the field of Rhinology reviewed the available literature with the aim of providing recommendations for the use of systemic steroids in treating upper airway disease.Peer reviewe