Mediterranean springs: Keystone ecosystems and biodiversity refugia threatened by global change.

Mediterranean spring ecosystems are unique habitats at the interface between surface water and groundwater. These ecosystems support a remarkable array of biodiversity and provide important ecological functions and ecosystem services. Spring ecosystems are influenced by abiotic, biotic, and anthropogenic factors such as the lithology of their draining aquifers, their climate, and the land use of their recharge area, all of which affect the water chemistry of the aquifer and the spring discharges. One of the most relevant characteristics of spring ecosystems is the temporal stability of environmental conditions, including physicochemical features of the spring water, across seasons and years. This stability allows a wide range of species to benefit from these ecosystems (particularly during dry periods), fostering an unusually high number of endemic species. However, global change poses important threats to these freshwater ecosystems. Changes in temperature, evapotranspiration, and precipitation patterns can alter the water balance and chemistry of spring water. Eutrophication due to agricultural practices and emergent pollutants, such as pharmaceuticals, personal care products, and pesticides, is also a growing concern for the preservation of spring biodiversity. Here, we provide a synthesis of the main characteristics and functioning of Mediterranean spring ecosystems. We then describe their ecological value and biodiversity patterns and highlight the main risks these ecosystems face. Moreover, we identify existing knowledge gaps to guide future research in order to fully uncover the hidden biodiversity within these habitats and understand the main drivers that govern them. Finally, we provide a brief summary of recommended actions that should be taken to effectively manage and preserve Mediterranean spring ecosystems for future generations. Even though studies on Mediterranean spring ecosystems are still scarce, our review shows there are sufficient data to conclude that their future viability as functional ecosystems is under severe threat.

Face-to-face and online teaching experience on experimental animals and alternative methods with nursing students: a research study.

BACKGROUND: Animal models are increasingly used in Nursing science to study care approaches. Despite the scientific relevance and the ethical debate surrounding the use of experimental animals, there is a scarcity of scholarly literature exploring this topic in Nursing Schools. AIM: To evaluate perceptions and attitudes of nursing students enrolled in a Pharmacology course on the use of experimental animals and implementation of alternative methods, by comparing the experience for two academic years. An interdisciplinary collaboration has also been developed. METHODS: A descriptive cross-sectional, quantitative study was developed. Undergraduate nursing students were enrolled in the Pharmacology subject at the University of Leon (Spain). The study was carried out in the Pharmacology facilities. Students followed a two-session practical class regarding experimental animals and alternative methods in the Pharmacology course (Degree in Nursing) in two different academic years (2019-20/2020-21). At the end of the activity, they answered a questionnaire to assess their opinions on the use of experimental animals and alternative methods in Pharmacology and the 3Rs principle. RESULTS: A comparison of the students' perception with and without direct participation in the evaluation of promazine effects in mice was made. A total of 190 students participated in the teaching experience, providing high scores in all items (4-5 out of 5 points) regarding the teaching experience. Students became also aware of the advantages and disadvantages on the use of experimental animals, as well as the ethical considerations to bear in mind for their use and the need for alternative methods. CONCLUSIONS: In the students' opinion, the total replacement of animals by alternative techniques was very difficult, and they preferred to do the practice face-to-face. The alternative method designed was useful for the students to accept the employment of experimental animals in biomedical research and education, and know the legislation applied in the protection of animals.

Vitamin D receptor (VDR) expression in different molecular subtypes of canine mammary carcinoma.

BACKGROUND: The molecular-based classification of canine mammary carcinomas (CMCs) has been the focus of much current research. Both in canines and humans, the triple-negative (TN) molecular subtype of mammary cancer is defined by a lack of expression of progesterone receptor (PR), oestrogen receptor (ER) and HER2. It has a poor prognosis; no effective targeted therapy is available. Vitamin D displays anticarcinogenic properties, and the expression of its receptor (VDR) has been found in different molecular subtypes, being about 30-40 % of TN breast cancer (TNBC) positive to it. We assessed the VDR expression in the different molecular subtypes of 58 CMCs from 45 female dogs using an immunohistochemical panel for the molecular classification of included: PR, ER, HER2, cytokeratin (CK) 5, CK14, and Ki67. In addition, we studied the relationship among the molecular subtypes of CMCs and clinicopathologic parameters. RESULTS: Investigation showed VDR positivity in 45.0 % of the triple-negative CMCs (TNCMCs), 27.3 % of luminal B and 19.0 % of luminal A. Luminal A was the most molecular subtype represented of the total tumours (36.2 %), followed of TNCMCs (34.5 %), luminal B (20.7 %) and HER2-overexpression (10.3 %). Both HER2-overexpression and TNCMC subtypes were positively related to lymphatic invasion (P = 0.028), simple histologic subtype (P = 0.007), a higher histological grade (P = 0.045) and a trend to higher proliferation index (P = 0.09). CONCLUSIONS: The highest VDR expression was observed in TNCMC, being almost half of them (45 %) positive to this receptor. VDR expression was absent in HER2-overexpression tumours and low in luminal A and B molecular subtypes.

Mortality and critical conditions in COVID-19 patients at private hospitals: weekend effect?

OBJECTIVE: The aim of the study was to find factors associated with the mortality of admission to the intensive care unit (ICU) in patients with COVID-19. MATERIALS AND METHODS: Retrospective observational study with a database of 1987 patients with COVID-19 who had attended the emergency department of a private hospital network between February 2020 and April 2020 were analyzed. Clinical variables and some laboratory parameters were studied. The Charlson and Elixhauser comorbidity indices were calculated. The dependent variables were mortality and admission to the ICU. A descriptive and correlational analysis was performed. Logistic regression models and Kaplan-Meier survival curves were established. RESULTS: Positive correlations were observed between age, creatinine, and D-dimer levels, as well as with the scores obtained with the Charlson and Elixhauser indices. Differences in the levels of these parameters were also observed when analyzing variables such as mortality, sex or admission to the ICU. Mortality was associated with high creatinine and D-dimer levels and advanced age. Survival curves indicated longer survival in patients not admitted to the ICU, admitted to the hospital during the week, and in those with lower creatinine and D-dimer levels. CONCLUSIONS: Mortality in Spanish patients with COVID-19 admitted to private hospitals was associated with high creatinine and D-dimer levels and advanced age. Longer survival was obtained on weekdays. This study provides valuable information on the management and nursing care of these patients in order to optimize resources in pandemic situations.

Forest production efficiency increases with growth temperature.

Forest production efficiency (FPE) metric describes how efficiently the assimilated carbon is partitioned into plants organs (biomass production, BP) or-more generally-for the production of organic matter (net primary production, NPP). We present a global analysis of the relationship of FPE to stand-age and climate, based on a large compilation of data on gross primary production and either BP or NPP. FPE is important for both forest production and atmospheric carbon dioxide uptake. We find that FPE increases with absolute latitude, precipitation and (all else equal) with temperature. Earlier findings-FPE declining with age-are also supported by this analysis. However, the temperature effect is opposite to what would be expected based on the short-term physiological response of respiration rates to temperature, implying a top-down regulation of carbon loss, perhaps reflecting the higher carbon costs of nutrient acquisition in colder climates. Current ecosystem models do not reproduce this phenomenon. They consistently predict lower FPE in warmer climates, and are therefore likely to overestimate carbon losses in a warming climate.

A Versatile Approach to Access Trimetallic Complexes Based on Trisphosphinite Ligands.

A straightforward method for the preparation of trisphosphinite ligands in one step, using only commercially available reagents (1,1,1-tris(4-hydroxyphenyl)ethane and chlorophosphines) is described. We have made use of this approach to prepare a small family of four trisphosphinite ligands of formula [CH3C{(C6H4OR2)3], where R stands for Ph (1a), Xyl (1b, Xyl = 2,6-Me2-C6H3), iPr (1c), and Cy (1d). These polyfunctional phosphinites allowed us to investigate their coordination chemistry towards a range of late transition metal precursors. As such, we report here the isolation and full characterization of a number of Au(I), Ag(I), Cu(I), Ir(III), Rh(III) and Ru(II) homotrimetallic complexes, including the structural characterization by X-ray diffraction studies of six of these compounds. We have observed that the flexibility of these trisphosphinites enables a variety of conformations for the different trimetallic species.

Nitrate pollution reduces bryophyte diversity in Mediterranean springs.

Anthropogenic activities and intensive farming are causing nitrate pollution in groundwater bodies. These aquifers are drained by springs which, in the Mediterranean region, act as refugia for preserving biodiversity of species that need continuous water. Some springs are also used for drinking water for wild animals, livestock and humans, so if their water quality is compromised it can become a threat to public health. However, the impact of nitrate pollution on these biotic communities remains unknown. We sampled 338 assemblages of aquatic and semi-aquatic bryophytes (i.e., hygrophytic mosses and liverworts) growing in springs in a gradient of water conductivity, nitrate concentration and climate and distributed across the north-east of the Iberian Peninsula to investigate the impact of nitrate pollution on the diversity of bryophytes and moss functional traits in Mediterranean springs. Based on previous literature suggesting that increased nitrogen load decreases biodiversity in grasslands and freshwater ecosystems, we hypothesised that water nitrate pollution in springs decreases bryophyte diversity at the local and regional scales. Our results indicated that, at the local scale (spring), nitrate pollution reduced the number and the likelihood of finding a rare species in springs. Rare species were found in 4% of the springs with nitrate above 50 mg L-1 but in 32% of the springs with nitrate below 50 mg L-1. Moss, liverwort and overall bryophyte diversity were not directly affected by nitrate at the local scale but nitrate consistently decreased diversity of mosses, liverworts and rare bryophyte species at the regional scale. We also found that warmer and drier springs presented fewer bryophyte species. Our results show that the combination of nitrate pollution, increasing temperature and drought could severely threaten bryophyte diversity in Mediterranean springs. Our results indicate that the absence of rare bryophytes could be used as a bioindicator of nitrate pollution in springs.

Nutrient scarcity as a selective pressure for mast seeding.

Mast seeding is one of the most intriguing reproductive traits in nature. Despite its potential drawbacks in terms of fitness, the widespread existence of this phenomenon suggests that it should have evolutionary advantages under certain circumstances. Using a global dataset of seed production time series for 219 plant species from all of the continents, we tested whether masting behaviour appears predominantly in species with low foliar nitrogen and phosphorus concentrations when controlling for local climate and productivity. Here, we show that masting intensity is higher in species with low foliar N and P concentrations, and especially in those with imbalanced N/P ratios, and that the evolutionary history of masting behaviour has been linked to that of nutrient economy. Our results support the hypothesis that masting is stronger in species growing under limiting conditions and suggest that this reproductive behaviour might have evolved as an adaptation to nutrient limitations and imbalances.

Some comments on Bitcoin market (in)efficiency.

In this paper, we explore the (in)efficiency of the continuum Bitcoin-USD market in the period ranging from mid 2010 to early 2019. To deal with, we dynamically analyse the evolution of the self-similarity exponent of Bitcoin-USD daily returns via accurate FD4 approach by a 512 day sliding window with overlapping data. Further, we define the memory indicator by the difference between the self-similarity exponent of Bitcoin-USD series and the self-similarity index of its shuffled series. We also carry out additional analyses via FD4 approach by sliding windows of sizes equal to 64, 128, 256, and 1024 days, and also via FD algorithm for values of q equal to 1 and 2 (and sliding windows equal to 512 days). Moreover, we explored the evolution of the self-similarity exponent of actual S&P500 series via FD4 algorithm by sliding windows of sizes equal to 256 and 512 days. In all the cases, the obtained results were found to be similar to our first analysis. We conclude that the self-similarity exponent of the BTC-USD (resp., S&P500) series stands above 0.5. However, this is not due to the presence of significant memory in the series but to its underlying distribution. In fact, it holds that the self-similarity exponent of BTC-USD (resp., S&P500) series is similar or lower than the self-similarity index of a random series with the same distribution. As such, several periods with significant antipersistent memory in BTC-USD (resp., S&P500) series are distinguished.

Medicamentos genéricos, ¿equivalentes a los de referencia? ¿qué está sucediendo? / Generic drugs, equivalent to reference drugs? What is happening?

La Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) ha emitido en los últimos meses una serie de alertas sanitarias retirando del mercado diversos lotes de medicamentos genéricos que contenían el principio activo valsartán, y más recientemente al irbesartán, debido a la presencia de una impureza, la N-nitrosodimetila-mina (NDMA), una sustancia tóxica para el hígado y probablemente carcinogénica. Como consecuencia de esta situación, se ha avivado la polémica que las diferencias entre medicamentos genéricos e innovadores despierta en la opinión pública y en algunos ámbitos profesionales. Los medicamentos genéricos con-tienen los mismos principios activos y se presentan en la misma forma farmacéutica, comparten calidad, seguridad y eficacia, y están sometidos a los mismos controles que los de referencia. Sin embargo, mientras que para acreditar la eficacia y la seguridad de un medicamento de referencia es necesario realizar ensayos clínicos, los genéricos pueden hacerlo demostrando su bioequivalencia con un medicamento ya autorizado. Las alertas emitidas demuestran que el sistema de control rutinario de fármacos funciona bien, pero también ha servido para dar un aviso a las administraciones públicas, quienes deben comprender que no se puede centrar la política de medicamentos únicamente en el ahorro y en precios bajos, ya que esto muchas veces conlleva riesgos para los con-sumidores. Sin duda, deben intensificarse tan-to las regulaciones sanitarias como la farmacovigilancia, para poder identificar a tiempo este tipo de riesgos sanitarios y prevenirlos o, al menos, reducirlos

The Spanish Agency for Medicines and Health Products (AEMPS) has issued a series of health alerts in the last few months removing from the market several batches of generic medicines containing the active ingredient valsartan, and more recently irbesartan, due to the presence of an impurity, N-nitrosodimethylamine (NDMA), toxic to the liver and probably carcinogenic. As a result of this situation, the controversy that the differences between generic and innovative medicines arouse in public opinion and in some professional fields has been stoked. Generic medicines contain the same active ingredients and are presented in the same pharmaceutical form, share quality, safety and efficacy, and are subject to the same controls as the reference ones. However, while accrediting the efficacy and safety of a reference medicine requires clinical trials, generics can do so by demonstrating their bioequivalence with an already authorized medicine. The warnings issued show that the routine drug control system works well, but it has also served to give notice to public administrations, who must understand that the drug policy can not be focused solely on savings and low prices, since that this often entails risks for consumers. Undoubtedly, both sanitary regulations and pharmacovigilance must be intensified in order to identify these types of health risks in time and prevent them or, at least, reduce them

Author Correction: Unprecedented rains decimate surface microbial communities in the hyperarid core of the Atacama Desert.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

More than seventy years from a milestone in fractal geometry: Moran's theorem.

In this paper, we re-explore in detail the techniques employed in P. A. P. Moran's original proof for a key result in fractal geometry allowing the calculation of the Hausdorff dimension of attractors of iterated function systems constructed by similitudes.

Unprecedented rains decimate surface microbial communities in the hyperarid core of the Atacama Desert.

The hyperarid core of the Atacama Desert, the driest and oldest desert on Earth, has experienced a number of highly unusual rain events over the past three years, resulting in the formation of previously unrecorded hypersaline lagoons, which have lasted several months. We have systematically analyzed the evolution of the lagoons to provide quantitative field constraints of large-scale impacts of the rains on the local microbial communities. Here we show that the sudden and massive input of water in regions that have remained hyperarid for millions of years is harmful for most of the surface soil microbial species, which are exquisitely adapted to survive with meager amounts of liquid water, and quickly perish from osmotic shock when water becomes suddenly abundant. We found that only a handful of bacteria, remarkably a newly identified species of Halomonas, remain metabolically active and are still able to reproduce in the lagoons, while no archaea or eukaryotes were identified. Our results show that the already low microbial biodiversity of extreme arid regions greatly diminishes when water is supplied quickly and in great volumes. We conclude placing our findings in the context of the astrobiological exploration of Mars, a hyperarid planet that experienced catastrophic floodings in ancient times.

Burnout y engagement en estudiantes universitarios de enfermería / Burnout and engagement among university nursing students

Los universitarios se encuentran sometidos a cargas académicas prolongadas que ocuparan la mayor parte de su tiempo. La capacidad para hacer frente a estas situaciones de estrés durante su formación, dependerá ente otras cosas, de la disposición personal para afrontar las demandas académicas. Objetivo: Describir el nivel de burnout (agotamiento, cinismo y eficacia académica) y el compromiso académico a través de la variable engagement (absorción, dedicación y vigor), además de analizar las asociaciones, relaciones y predicciones entre estas variables en estudiantes de Enfermería. Material y método. Estudio descriptivo transversal en 1009 sujetos. Instrumentos de recogida de datos: Maslach Burnout Inventory y Utrech Work Engagement en versión estudiantes. Resultados: Las dimensiones del burnout y engagement correlacionan entre sí. A mayor eficacia académica menos agotamiento y cinismo y mayor puntuación en todas las dimensiones del engagement académico. El vigor y la dedicación predicen puntuaciones más altas en eficacia académica. Las mujeres se perciben con puntuaciones más bajas en cinismo y más altas en eficacia académica, absorción y dedicación. Conclusiones: Los alumnos muestran más burnout cuando manifiestan altas puntuaciones de agotamiento y cinismo y bajas en eficacia académica, además valores altos en las tres dimensiones del engagement indican alto compromiso con sus estudios. La relación entre estas variables pone de manifiesto la diferencia entre hombres y mujeres y la influencia positiva del engagement en la eficacia académica del estudiante. El fomento de engagement puede ser una oportunidad para superar las tareas académicas y para enfrentarse al mundo laboral con mayor probabilidad de éxito

University students are tasked with a protracted academic workload that occupies the greater part of their time. Their ability to cope with the stress this entails during their degree course will partly depend on their personal response to these academic demands. Objective: to describe nursing students’ level of burnout (exhaustion, cynicism and academic efficacy) and academic engagement through the variable engagement (absorption, dedication and vigour), and to analyse associations, relations and predictions between these variables. Materials and method: cross-sectional descriptive study with 1009 subjects. Data collection instruments: student versions of the Maslach Burnout Inventory and the Utrecht Work Engagement Scale. Results: the dimensions of burnout and engagement correlated with each other. The higher the score for academic efficacy, the lower the scores for exhaustion and cynicism and the higher the score in all dimensions of academic engagement. Vigour and dedication predicted higher scores for academic efficacy. Females' self-perceptions indicated lower scores for cynicism and higher scores for academic efficacy, absorption and dedication. Conclusions: students evidenced more burnout when they obtained high scores for exhaustion and cynicism and low scores for academic efficacy. In addition, high scores for the three dimensions of engagement indicated high commitment to their studies. The relationship between these variables indicates a difference between males and females and a positive influence of engagement on students' academic efficacy. Promoting engagement could help students to deal with academic tasks and enter the labour market with a greater probability of success

Vitamin D receptor expression in canine mammary gland and relationship with clinicopathological parameters and progesterone/oestrogen receptors.

The vitamin D receptor (VDR) belongs to the nuclear class II receptor family. VDR is a ligand transcription factor and mediates the actions of calcitriol, the active product of vitamin D synthesis. Nowadays, it is known that the biological actions of calcitriol include the capacity to modulate cancer features, such as proliferation and differentiation, apoptosis, angiogenesis, invasion and metastasis. VDR expression has been demonstrated in human breast cancer and vitamin D has emerged as a promising targeted therapy. We analyse the VDR expression in normal and neoplastic canine mammary tissue samples and its relationship with clinicopathological parameters and progesterone/oestrogens receptors (PR/ER). Expression of VDR, Ki67 (to evaluate the proliferation index, PI), PR and ER was assessed in 50 mammary gland tissue samples from 41 female dogs by immunohistochemistry. VDR-positive staining was found in the nuclei of both myoepithelial and luminal epithelial cell layers. VDR expression was higher in normal mammary tissue (37/37 cases, 100%) then followed by benign tumours (6/15 cases, 40%) and malignant tumours (9/34 cases, 26.5%) (P = .001). Female dogs aged ≥10 years had lower VDR expression compared with dogs younger (P = .017). Relationship between VDR and breed, number of tumours, tumour size, histologic subtype, histologic grade of malignancy, PI and PR and ER expression was not observed. Studies with more samples are necessary to further evaluate the possible role of VDR in the biological behaviour of canine mammary tumours, and to corroborate the possibility to use the dog as model for human breast cancer.

Atmospheric deposition, CO2, and change in the land carbon sink.

Concentrations of atmospheric carbon dioxide (CO2) have continued to increase whereas atmospheric deposition of sulphur and nitrogen has declined in Europe and the USA during recent decades. Using time series of flux observations from 23 forests distributed throughout Europe and the USA, and generalised mixed models, we found that forest-level net ecosystem production and gross primary production have increased by 1% annually from 1995 to 2011. Statistical models indicated that increasing atmospheric CO2 was the most important factor driving the increasing strength of carbon sinks in these forests. We also found that the reduction of sulphur deposition in Europe and the USA lead to higher recovery in ecosystem respiration than in gross primary production, thus limiting the increase of carbon sequestration. By contrast, trends in climate and nitrogen deposition did not significantly contribute to changing carbon fluxes during the studied period. Our findings support the hypothesis of a general CO2-fertilization effect on vegetation growth and suggest that, so far unknown, sulphur deposition plays a significant role in the carbon balance of forests in industrialized regions. Our results show the need to include the effects of changing atmospheric composition, beyond CO2, to assess future dynamics of carbon-climate feedbacks not currently considered in earth system/climate modelling.

Global patterns of phosphatase activity in natural soils.

Soil phosphatase levels strongly control the biotic pathways of phosphorus (P), an essential element for life, which is often limiting in terrestrial ecosystems. We investigated the influence of climatic and soil traits on phosphatase activity in terrestrial systems using metadata analysis from published studies. This is the first analysis of global measurements of phosphatase in natural soils. Our results suggest that organic P (Porg), rather than available P, is the most important P fraction in predicting phosphatase activity. Structural equation modeling using soil total nitrogen (TN), mean annual precipitation, mean annual temperature, thermal amplitude and total soil carbon as most available predictor variables explained up to 50% of the spatial variance in phosphatase activity. In this analysis, Porg could not be tested and among the rest of available variables, TN was the most important factor explaining the observed spatial gradients in phosphatase activity. On the other hand, phosphatase activity was also found to be associated with climatic conditions and soil type across different biomes worldwide. The close association among different predictors like Porg, TN and precipitation suggest that P recycling is driven by a broad scale pattern of ecosystem productivity capacity.

Near-Earth object hazardous impact: A Multi-Criteria Decision Making approach.

The impact of a near-Earth object (NEO) may release large amounts of energy and cause serious damage. Several NEO hazard studies conducted over the past few years provide forecasts, impact probabilities and assessment ratings, such as the Torino and Palermo scales. These high-risk NEO assessments involve several criteria, including impact energy, mass, and absolute magnitude. The main objective of this paper is to provide the first Multi-Criteria Decision Making (MCDM) approach to classify hazardous NEOs. Our approach applies a combination of two methods from a widely utilized decision making theory. Specifically, the Analytic Hierarchy Process (AHP) methodology is employed to determine the criteria weights, which influence the decision making, and the Technique for Order Performance by Similarity to Ideal Solution (TOPSIS) is used to obtain a ranking of alternatives (potentially hazardous NEOs). In addition, NEO datasets provided by the NASA Near-Earth Object Program are utilized. This approach allows the classification of NEOs by descending order of their TOPSIS ratio, a single quantity that contains all of the relevant information for each object.

Dysexecutive syndrome in amnesic mild cognitive impairment: a multicenter study.

BACKGROUND: Executive functions (EF) in Alzheimer's disease (AD), classically related to the prefrontal cortex, have been forgotten in mild stages, given more importance to temporal lobe associated disorders, such as memory. The study of disexecutive syndrome (DS) has been relegated to advanced stages of the disease. Our goal is to demonstrate that EF are already present in amnesic mild cognitive impairment (aMCI). Furthermore, we are interested in knowing whether poor scores in EF tests are related to the progression to AD or another kind of dementia. METHODS: We studied patients with aMCI (n = 81) and healthy controls (n = 142) from neurological departments of several centers of Basque Country with a cross-sectional design. Patients underwent a complete neuropsychological evaluation, neuroimaging testing APOE genotype and 3 year of prospective follow-up. RESULTS: In the first visit, patients with aMCI showed more alterations in tests that evaluate EF such as Stroop, trail-making and categorical verbal fluency. More alterations were also found in NPI scale (P <0.05). Stroop and Trail-Making test were not associated with the future development of AD, but fluency (p = 0.01) and apathy (p = 0.031) did. No patient developed a different kind of dementia different from AD. CONCLUSIONS: DS is a broad concept not confined to frontal lobes, and can be found in early stages of aMCI. DS impacts negatively on patient autonomy and may have prognostic value.