Polarized citizen preferences for the ethical allocation of scarce medical resources in 20 countries.

This is the final version. Available from SAGE Publications via the DOI in this record. Data Availability Statement: Data and code are open and available at https://github.com/ bencebago/ventilators.Objective. When medical resources are scarce, clinicians must make difficult triage decisions. When these decisions affect public trust and morale, as was the case during the COVID-19 pandemic, experts will benefit from knowing which triage metrics have citizen support. Design. We conducted an online survey in 20 countries, comparing support for 5 common metrics (prognosis, age, quality of life, past and future contribution as a health care worker) to a benchmark consisting of support for 2 no-triage mechanisms (first-come-first-served and random allocation). Results. We surveyed nationally representative samples of 1000 citizens in each of Brazil, France, Japan, and the United States and also self-selected samples from 20 countries (total N = 7599) obtained through a citizen science website (the Moral Machine). We computed the support for each metric by comparing its usability to the usability of the 2 no-triage mechanisms. We further analyzed the polarizing nature of each metric by considering its usability among participants who had a preference for no triage. In all countries, preferences were polarized, with the 2 largest groups preferring either no triage or extensive triage using all metrics. Prognosis was the least controversial metric. There was little support for giving priority to healthcare workers. Conclusions. It will be difficult to define triage guidelines that elicit public trust and approval. Given the importance of prognosis in triage protocols, it is reassuring that it is the least controversial metric. Experts will need to prepare strong arguments for other metrics if they wish to preserve public trust and morale during health crises. Highlights: We collected citizen preferences regarding triage decisions about scarce medical resources from 20 countries.We find that citizen preferences are universally polarized.Citizens either prefer no triage (random allocation or first-come-first served) or extensive triage using all common triage metrics, with "prognosis" being the least controversial.Experts will need to prepare strong arguments to preserve or elicit public trust in triage decisions

Long term time variability of cosmic rays and possible relevance to the development of life on Earth

An analysis is made of the manner in which the cosmic ray intensity at Earth has varied over its existence and its possible relevance to both the origin and the evolution of life. Much of the analysis relates to the 'high energy' cosmic rays ($E>10^{14}eV;=0.1PeV$) and their variability due to the changing proximity of the solar system to supernova remnants which are generally believed to be responsible for most cosmic rays up to PeV energies. It is pointed out that, on a statistical basis, there will have been considerable variations in the likely 100 My between the Earth's biosphere reaching reasonable stability and the onset of very elementary life. Interestingly, there is the increasingly strong possibility that PeV cosmic rays are responsible for the initiation of terrestrial lightning strokes and the possibility arises of considerable increases in the frequency of lightnings and thereby the formation of some of the complex molecules which are the 'building blocks of life'. Attention is also given to the well known generation of the oxides of nitrogen by lightning strokes which are poisonous to animal life but helpful to plant growth; here, too, the violent swings of cosmic ray intensities may have had relevance to evolutionary changes. A particular variant of the cosmic ray acceleration model, put forward by us, predicts an increase in lightning rate in the past and this has been sought in Korean historical records. Finally, the time dependence of the overall cosmic ray intensity, which manifests itself mainly at sub-10 GeV energies, has been examined. The relevance of cosmic rays to the 'global electrical circuit' points to the importance of this concept.Comment: 18 pages, 5 figures, accepted by 'Surveys in Geophysics

Intra-tumour heterogeneity is one of the main sources of inter-observer variation in scoring stromal tumour infiltrating lymphocytes in triple negative breast cancer

Stromal tumour infiltrating lymphocytes (sTILs) are a strong prognostic marker in triple negative breast cancer (TNBC). Consistency scoring sTILs is good and was excellent when an internet-based scoring aid developed by the TIL-WG was used to score cases in a reproducibility study. This study aimed to evaluate the reproducibility of sTILs assessment using this scoring aid in cases from routine practice and to explore the potential of the tool to overcome variability in scoring. Twenty-three breast pathologists scored sTILs in digitized slides of 49 TNBC biopsies using the scoring aid. Subsequently, fields of view (FOV) from each case were selected by one pathologist and scored by the group using the tool. Inter-observer agreement was good for absolute sTILs (ICC 0.634, 95% CI 0.539–0.735, p < 0.001) but was poor to fair using binary cutpoints. sTILs heterogeneity was the main contributor to disagreement. When pathologists scored the same FOV from each case, inter-observer agreement was excellent for absolute sTILs (ICC 0.798, 95% CI 0.727–0.864, p < 0.001) and good for the 20% (ICC 0.657, 95% CI 0.561–0.756, p < 0.001) and 40% (ICC 0.644, 95% CI 0.546–0.745, p < 0.001) cutpoints. However, there was a wide range of scores for many cases. Reproducibility scoring sTILs is good when the scoring aid is used. Heterogeneity is the main contributor to variance and will need to be overcome for analytic validity to be achieved

Age, Health and Life Satisfaction Among Older Europeans

In this paper we investigate how age affects the self-reported level of life satisfaction among the elderly in Europe. By using a vignette approach, we find evidence that age influences life satisfaction through two counterbalancing channels. On the one hand, controlling for the effects of all other variables, the own perceived level of life satisfaction increases with age. On the other hand, given the same true level of life satisfaction, older respondents are more likely to rank themselves as “dissatisfied” with their life than younger individuals. Detrimental health conditions and physical limitations play a crucial role in explaining scale biases in the reporting style of older individuals

Predicting for activity of second-line trastuzumab-based therapy in her2-positive advanced breast cancer

<p>Abstract</p> <p>Background</p> <p>In Her2-positive advanced breast cancer, the upfront use of trastuzumab is well established. Upon progression on first-line therapy, patients may be switched to lapatinib. Others however remain candidates for continued antibody treatment (treatment beyond progression). Here, we aimed to identify factors predicting for activity of second-line trastuzumab-based therapy.</p> <p>Methods</p> <p>Ninety-seven patients treated with > 1 line of trastuzumab-containing therapy were available for this analysis. Her2-status was determined by immunohistochemistry and re-analyzed by FISH if a score of 2+ was gained. Time to progression (TTP) on second-line therapy was defined as primary study endpoint. TTP and overall survival (OS) were estimated using the Kaplan-Meier product limit method. Multivariate analyses (Cox proportional hazards model, multinomial logistic regression) were applied in order to identify factors associated with TTP, response, OS, and incidence of brain metastases. <it>p </it>values < 0.05 were considered to indicate statistical significance.</p> <p>Results</p> <p>Median TTP on second-line trastuzumab-based therapy was 7 months (95% CI 5.74-8.26), and 8 months (95% CI 6.25-9.74) on first-line, respectively (n.s.). In the multivariate models, none of the clinical or histopthological features could reliably predict for activity of second-line trastuzumab-based treatment. OS was 43 months suggesting improved survival in patients treated with trastuzumab in multiple-lines. A significant deterioration of cardiac function was observed in three patients; 40.2% developed brain metastases while on second-line trastuzumab or thereafter.</p> <p>Conclusion</p> <p>Trastuzumab beyond progression showed considerable activity. None of the variables investigated correlated with activity of second-line therapy. In order to predict for activity of second-line trastuzumab, it appears necessary to evaluate factors known to confer trastuzumab-resistance.</p

A new species of Stenobiella Tillyard (Neuroptera, Berothidae) from Australia

Stenobiella variola sp. n., a new species of beaded lacewing (Neuroptera: Berothidae), is described and figured from south-eastern Australia. A preliminary key to Stenobiella species is presented

The evolution of socioeconomic status-related inequalities in maternal health care utilization: evidence from Zimbabwe, 1994-2011

Background: Inequalities in maternal health care are pervasive in the developing world, a fact that has led to questions about the extent of these disparities across socioeconomic groups. Despite a growing literature on maternal health across Sub-Saharan African countries, relatively little is known about the evolution of these inequalities over time for specific countries. This study sought to quantify and explain the observed differences in prenatal care use and professional delivery assistance in Zimbabwe. Methods: The empirical analysis uses four rounds of the nationwide Zimbabwe Demographic and Health Survey administered in 1994, 1999, 2005/06 and 2010/11. Two binary indicators were used as measures of maternal health care utilization; (1) the receipt of four or more antenatal care visits and (2) receiving professional delivery assistance for the most recent pregnancy. We measure inequalities in maternal health care use using the Erreygers corrected concentration index. A decomposition analysis was conducted to determine the underlying drivers of the measured disparities. Results: The computed concentration indices for professional delivery assistance and prenatal care reveal a mostly pro-rich distribution of inequalities between 1994 and 2011. Particularly, the concentration index [95% confidence interval] for the receipt of prenatal care was 0.111 [0.056, 0.171] in 2005/06 and 0.094 [0.057, 0.138] in 2010/11. For professional delivery assistance, the concentration index stood at 0.286 [0.244, 0.329] in 2005/06 and 0.324 [0.283, 0.366] in 2010/11. The pro-rich inequality was also increasing in both rural and urban areas over time. The decomposition exercise revealed that wealth, education, religion and information access were the underlying drivers of the observed inequalities in maternal health care. Conclusions: In Zimbabwe, socioeconomic disparities in maternal health care use are mostly pro-rich and have widened over time regardless of the location of residence. Overall, we established that inequalities in wealth and education are amongst the top drivers of the observed disparities in maternal health care. These findings suggest that addressing inequalities in maternal health care utilization requires coordinated public policies targeting the more poor and vulnerable segments of the population in Zimbabwe

Arbuscular Mycorrhizal Fungi and Plant Chemical Defence : Effects of Colonisation on Aboveground and Belowground Metabolomes

Arbuscular mycorrhizal fungal (AMF) colonisation of plant roots is one of the most ancient and widespread interactions in ecology, yet the systemic consequences for plant secondary chemistry remain unclear. We performed the first metabolomic investigation into the impact of AMF colonisation by Rhizophagus irregularis on the chemical defences, spanning above- and below-ground tissues, in its host-plant ragwort (Senecio jacobaea). We used a non-targeted metabolomics approach to profile, and where possible identify, compounds induced by AMF colonisation in both roots and shoots. Metabolomics analyses revealed that 33 compounds were significantly increased in the root tissue of AMF colonised plants, including seven blumenols, plant-derived compounds known to be associated with AMF colonisation. One of these was a novel structure conjugated with a malonyl-sugar and uronic acid moiety, hitherto an unreported combination. Such structural modifications of blumenols could be significant for their previously reported functional roles associated with the establishment and maintenance of AM colonisation. Pyrrolizidine alkaloids (PAs), key anti-herbivore defence compounds in ragwort, dominated the metabolomic profiles of root and shoot extracts. Analyses of the metabolomic profiles revealed an increase in four PAs in roots (but not shoots) of AMF colonised plants, with the potential to protect colonised plants from below-ground organisms