"The missing ingredient":The patient perspective of health related quality of life in bronchiectasis: a qualitative study

Abstract Background Bronchiectasis is a heterogeneous disease which affects quality of life. Measuring symptoms and quality of life has proved challenging and research is limited by extrapolation of questionnaires and treatments from other diseases. The objective of this study was to identify the major contributors to quality of life in bronchiectasis and to evaluate existing health related quality of life questionnaires in bronchiectasis. Methods Eight adults with bronchiectasis participated in one to one semi-structured interviews. These were recorded and transcribed verbatim. Thematic analysis was used to identify core themes relevant to disease burden and impact. Participant views on current health related quality of life questionnaires were also surveyed. Results Bronchiectasis symptoms are highly individual. Core themes identified were symptom burden, symptom variation, personal measurement, quality of life and control of symptoms. Themes contributing to quality of life were: social embarrassment, sleep disturbance, anxiety and modification of daily and future activities. Evaluation of 4 existing questionnaires established their individual strengths and weaknesses. A synthesis of the participants’ perspective identified desirable characteristics to guide future tool development. Conclusions: This qualitative study has identified core themes associated with symptoms and quality of life in bronchiectasis. Current treatments and quality of life tools do not fully address or capture the burden of disease in bronchiectasis from the patients’ perspective

Evidence based medicine as science

Evidence based medicine has claimed to be science on a number of occasions but it is not clear that this status is deserved. Within philosophy of science four main theories about the nature of science are historically recognised: inductivism, falsificationism, Kuhnian paradigms and research programmes. If evidence based medicine is science knowledge claims should be derived using a process that corresponds to one of these theories. This paper analyses whether this is the case. In the first section, different theories about the nature of science are introduced. In the second section, the claim that evidence based medicine is science is reinterpreted as the claim that knowledge claims derived from randomised controlled trails and meta-analyses are science. In the third section the knowledge claims valued within evidence based medicine are considered from the perspective of inductivism, falsificationism, Kuhnian paradigms and research programmes. In the final section possible counter arguments are considered. It is argued that the knowledge claims valued by evidence based medicine are not justified using inductivism, falsificationism, Kuhnian paradigms or research programmes. If these are the main criteria for evaluating if something is science or not, evidence based medicine does not meet these criteria

ESTRO-EANO guideline on target delineation and radiotherapy details for glioblastoma

BACKGROUND AND PURPOSE Target delineation in glioblastoma is still a matter of extensive research and debate. This guideline aims to update the existing joint European consensus on delineation of the clinical target volume (CTV) in adult glioblastoma patients. MATERIAL AND METHODS The ESTRO Guidelines Committee identified 14 European experts in close interaction with the ESTRO clinical committee and EANO who discussed and analysed the body of evidence concerning contemporary glioblastoma target delineation, then took part in a two-step modified Delphi process to address open questions. RESULTS Several key issues were identified and are discussed including i) pre-treatment steps and immobilisation, ii) target delineation and the use of standard and novel imaging techniques, and iii) technical aspects of treatment including planning techniques and fractionation. Based on the EORTC recommendation focusing on the resection cavity and residual enhancing regions on T1-sequences with the addition of a reduced 15 mm margin, special situations are presented with corresponding potential adaptations depending on the specific clinical situation. CONCLUSIONS The EORTC consensus recommends a single clinical target volume definition based on postoperative contrast-enhanced T1 abnormalities, using isotropic margins without the need to cone down. A PTV margin based on the individual mask system and IGRT procedures available is advised; this should usually be no greater than 3 mm when using IGRT

Scientific discovery as a combinatorial optimisation problem: How best to navigate the landscape of possible experiments?

A considerable number of areas of bioscience, including gene and drug discovery, metabolic engineering for the biotechnological improvement of organisms, and the processes of natural and directed evolution, are best viewed in terms of a ‘landscape’ representing a large search space of possible solutions or experiments populated by a considerably smaller number of actual solutions that then emerge. This is what makes these problems ‘hard’, but as such these are to be seen as combinatorial optimisation problems that are best attacked by heuristic methods known from that field. Such landscapes, which may also represent or include multiple objectives, are effectively modelled in silico, with modern active learning algorithms such as those based on Darwinian evolution providing guidance, using existing knowledge, as to what is the ‘best’ experiment to do next. An awareness, and the application, of these methods can thereby enhance the scientific discovery process considerably. This analysis fits comfortably with an emerging epistemology that sees scientific reasoning, the search for solutions, and scientific discovery as Bayesian processes

What kind of evidence is it that Evidence-Based Medicine advocates want health care providers and consumers to pay attention to?

BACKGROUND: In 1992, Evidence-Based Medicine advocates proclaimed a "new paradigm", in which evidence from health care research is the best basis for decisions for individual patients and health systems. Hailed in New York Times Magazine in 2001 as one of the most influential ideas of the year, this approach was initially and provocatively pitted against the traditional teaching of medicine, in which the key elements of knowing for clinical purposes are understanding of basic pathophysiologic mechanisms of disease coupled with clinical experience. This paper reviews the origins, aspirations, philosophical limitations, and practical challenges of evidence-based medicine. DISCUSSION: EBM has long since evolved beyond its initial (mis)conception, that EBM might replace traditional medicine. EBM is now attempting to augment rather than replace individual clinical experience and understanding of basic disease mechanisms. EBM must continue to evolve, however, to address a number of issues including scientific underpinnings, moral stance and consequences, and practical matters of dissemination and application. For example, accelerating the transfer of research findings into clinical practice is often based on incomplete evidence from selected groups of people, who experience a marginal benefit from an expensive technology, raising issues of the generalizability of the findings, and increasing problems with how many and who can afford the new innovations in care. SUMMARY: Advocates of evidence-based medicine want clinicians and consumers to pay attention to the best findings from health care research that are both valid and ready for clinical application. Much remains to be done to reach this goal

Cross-cultural generalizability of suicide first aid actions: an analysis of agreement across expert consensus studies from a range of countries and cultures

Background A number of Delphi expert consensus studies have been carried out with different countries and cultural groups to develop guidelines on how a member of the public should provide assistance to a person who is suicidal. The present study aimed to determine whether cross-culturally generalizable suicide first aid actions are possible by comparing agreement across these Delphi studies. Methods Data on endorsement rates for items were compared across six Delphi studies. These studies involved panels of professionals and consumer advocates from English-speaking countries, professionals from Sri Lanka, professionals from Japan, professionals from India, professionals from the Philippines, and professionals and consumer advocates in refugee and immigrant mental health. Correlations were calculated between item endorsement rates across panels. Results There were 18 items that were highly endorsed across all eight of the Delphi panels and an additional 15 items highly endorsed across the panels from the three lower middle-income countries (India, Philippines and Sri Lanka). Correlations across panels in item endorsement rates were all 0.60 or above, but were higher between panels from countries that are socioeconomically similar. Conclusions There is broad agreement across the diverse expert panels about what are appropriate suicide first aid actions for members of the public, indicating that cross-cultural generalizability is possible. However, there is also some cultural specificity, indicating the need for local tailoring

Learning robotics: a review

Purpose of Review: With the growing interest for STEM/STEAM, new robotic platforms are being created with different characteristics, extras and options. There are so many diverse solutions, that it is difficult for a teacher/student to choose the ideal one. This paper intends to provide an analysis to the most common robotic platforms existent on the market. The same is happening regarding robotic events all around the world, with objectives so distinctive, and with complexity from easy to very difficult. This paper also describes some of those events which occur in many countries. Recent Findings: As the literature is showing, there has been a visible effort from schools and educators to teach robotics from very young ages, not only because robotics is the future, but also as a tool to teach STEM/STEAM areas. But as time progresses, the options for the right platforms also evolves making difficult to choose among them. Some authors opt to first choose a robotic platform and carry on from there. Others choose first a development environment and then look for which robots can be programmed from it. Summary: An actual review on learning robotics is here presented, firstly showing some literature background on history and trends of robotic platforms used in education in general, the different development environments for robotics and finishing on competitions and events. A comprehensive characterization list of robotic platforms along with robotic competitions and events is also shown

Bayesian versus frequentist statistical inference for investigating a one-off cancer cluster reported to a health department

Background. The problem of silent multiple comparisons is one of the most difficult statistical problems faced by scientists. It is a particular problem for investigating a one-off cancer cluster reported to a health department because any one of hundreds, or possibly thousands, of neighbourhoods, schools, or workplaces could have reported a cluster, which could have been for any one of several types of cancer or any one of several time periods. Methods. This paper contrasts the frequentist approach with a Bayesian approach for dealing with silent multiple comparisons in the context of a one-off cluster reported to a health department. Two published cluster investigations were re-analysed using the Dunn-Sidak method to adjust frequentist p-values and confidence intervals for silent multiple comparisons. Bayesian methods were based on the Gamma distribution. Results. Bayesian analysis with non-informative priors produced results similar to the frequentist analysis, and suggested that both clusters represented a statistical excess. In the frequentist framework, the statistical significance of both clusters was extremely sensitive to the number of silent multiple comparisons, which can only ever be a subjective "guesstimate". The Bayesian approach is also subjective: whether there is an apparent statistical excess depends on the specified prior. Conclusion. In cluster investigations, the frequentist approach is just as subjective as the Bayesian approach, but the Bayesian approach is less ambitious in that it treats the analysis as a synthesis of data and personal judgements (possibly poor ones), rather than objective reality. Bayesian analysis is (arguably) a useful tool to support complicated decision-making, because it makes the uncertainty associated with silent multiple comparisons explicit

Selective Ion Changes during Spontaneous Mitochondrial Transients in Intact Astrocytes

The bioenergetic status of cells is tightly regulated by the activity of cytosolic enzymes and mitochondrial ATP production. To adapt their metabolism to cellular energy needs, mitochondria have been shown to exhibit changes in their ionic composition as the result of changes in cytosolic ion concentrations. Individual mitochondria also exhibit spontaneous changes in their electrical potential without altering those of neighboring mitochondria. We recently reported that individual mitochondria of intact astrocytes exhibit spontaneous transient increases in their Na+ concentration. Here, we investigated whether the concentration of other ionic species were involved during mitochondrial transients. By combining fluorescence imaging methods, we performed a multiparameter study of spontaneous mitochondrial transients in intact resting astrocytes. We show that mitochondria exhibit coincident changes in their Na+ concentration, electrical potential, matrix pH and mitochondrial reactive oxygen species production during a mitochondrial transient without involving detectable changes in their Ca2+ concentration. Using widefield and total internal reflection fluorescence imaging, we found evidence for localized transient decreases in the free Mg2+ concentration accompanying mitochondrial Na+ spikes that could indicate an associated local and transient enrichment in the ATP concentration. Therefore, we propose a sequential model for mitochondrial transients involving a localized ATP microdomain that triggers a Na+-mediated mitochondrial depolarization, transiently enhancing the activity of the mitochondrial respiratory chain. Our work provides a model describing ionic changes that could support a bidirectional cytosol-to-mitochondria ionic communication