Understanding patients' experiences of the wish to hasten death: an updated and expanded systematic review and meta-ethnography

OBJECTIVES: Patients with advanced disease sometimes express a wish to hasten death (WTHD). In 2012, we published a systematic review and meta-ethnography of qualitative studies examining the experience and meaning of this phenomenon. Since then, new studies eligible for inclusion have been reported, including in Europe, a region not previously featured, and specifically in countries with different legal frameworks for euthanasia and assisted suicide. The aim of the present study was to update our previous review by including new research and to conduct a new analysis of available data on this topic. SETTING: Eligible studies originated from Australia, Canada, China, Germany, The Netherlands, Switzerland, Thailand and USA. PARTICIPANTS: Studies of patients with life-threatening conditions that had expressed the WTHD. DESIGN: The search strategy combined subject terms with free-text searching of PubMed MEDLINE, Web of Science, CINAHL and PsycInfo. The qualitative synthesis followed the methodology described by Noblit and Hare, using the 'adding to and revising the original' model for updating a meta-ethnography, proposed by France et al. Quality assessment was done using the Critical Appraisal Skills Programme checklist. RESULTS: 14 studies involving 255 participants with life-threatening illnesses were identified. Five themes emerged from the analysis: suffering (overarching theme), reasons for and meanings and functions of the WTHD and the experience of a timeline towards dying and death. In the context of advanced disease, the WTHD emerges as a reaction to physical, psychological, social and existential suffering, all of which impacts on the patient's sense of self, of dignity and meaning in life. CONCLUSIONS: The WTHD can hold different meanings for each individual-serving functions other than to communicate a genuine wish to die. Understanding the reasons for, and meanings and functions of, the WTHD is crucial for drawing up and implementing care plans to meet the needs of individual patients

Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma.

Background Glioblastoma (GBM) is one of the most aggressive and vascularized brain tumors in adults, with a median survival of 20.9 months. In newly diagnosed and recurrent GBM, bevacizumab demonstrated an increase in progression-free survival, but not in overall survival. Methods We conducted an in silico analysis of VEGF expression, in a cohort of 1082 glioma patients. Then, to determine whether appropriate bevacizumab dose adjustment could increase the anti-angiogenic response, we used in vitro and in vivo GBM models. Additionally, we analyzed VEGFA expression in tissue, serum, and plasma in a cohort of GBM patients before and during bevacizumab treatment. Results We identified that 20% of primary GBM did not express VEGFA suggesting that these patients would probably not respond to bevacizumab therapy as we proved in vitro and in vivo. We found that a specific dose of bevacizumab calculated based on VEGFA expression levels increases the response to treatment in cell culture and serum samples from mice bearing GBM tumors. Additionally, in a cohort of GBM patients, we observed a correlation of VEGFA levels in serum, but not in plasma, with bevacizumab treatment performance. Conclusions Our data suggest that bevacizumab dose adjustment could improve clinical outcomes in Glioblastoma treatment.post-print1360 K

Photoperiodic Modulation of Circadian Clock and Reproductive Axis Gene Expression in the Pre-Pubertal European Sea Bass Brain

The acquisition of reproductive competence requires the activation of the brain-pituitary-gonad (BPG) axis, which in most vertebrates, including fishes, is initiated by changes in photoperiod. In the European sea bass long-term exposure to continuous light (LL) alters the rhythm of reproductive hormones, delays spermatogenesis and reduces the incidence of precocious males. In contrast, an early shift from long to short photoperiod (AP) accelerates spermatogenesis. However, how photoperiod affects key genes in the brain to trigger the onset of puberty is still largely unknown. Here, we investigated if the integration of the light stimulus by clock proteins is sufficient to activate key genes that trigger the BPG axis in the European sea bass. We found that the clock genes clock, npas2, bmal1 and the BPG genes gnrh, kiss and kissr share conserved transcription factor frameworks in their promoters, suggesting co-regulation. Other gene promoters of the BGP axis were also predicted to be co-regulated by the same frameworks. Co-regulation was confirmed through gene expression analysis of brains from males exposed to LL or AP photoperiod compared to natural conditions: LL fish had suppressed gnrh1, kiss2, galr1b and esr1, while AP fish had stimulated npas2, gnrh1, gnrh2, kiss2, kiss1rb and galr1b compared to NP. It is concluded that fish exposed to different photoperiods present significant expression differences in some clock and reproductive axis related genes well before the first detectable endocrine and morphological responses of the BPG axis.European Community [222719 - LIFECYCLE]; Foundation for Science and Technology of Portugal (FCT) [SFRH/BPD/66742/2009, PEst-C/MAR/LA0015/2011]; Valencian Regional Goverment [Prometeo II/2014/051]; Spanish Ministry of Science and Innovation (MICINN) [CSD 2007-0002]info:eu-repo/semantics/publishedVersio

PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer

To identify a group of patients who might benefit from the addition of weekly paclitaxel to conventional anthracycline-containing chemotherapy as adjuvant therapy of node-positive operable breast cancer. The predictive value of PAM50 subtypes and the 11-gene proliferation score contained within the PAM50 assay were evaluated in 820 patients from the GEICAM/9906 randomized phase III trial comparing adjuvant FEC to FEC followed by weekly paclitaxel (FEC-P). Multivariable Cox regression analyses of the secondary endpoint of overall survival (OS) were performed to determine the significance of the interaction between treatment and the (1) PAM50 subtypes, (2) PAM50 proliferation score, and (3) clinical and pathological variables. Similar OS analyses were performed in 222 patients treated with weekly paclitaxel versus paclitaxel every 3 weeks in the CALGB/9342 and 9840 metastatic clinical trials. In GEICAM/9906, with a median follow up of 8.7 years, OS of the FEC-P arm was significantly superior compared to the FEC arm (unadjusted HR = 0.693, p = 0.013). A benefit from paclitaxel was only observed in the group of patients with a low PAM50 proliferation score (unadjusted HR = 0.23, p < 0.001; and interaction test, p = 0.006). No significant interactions between treatment and the PAM50 subtypes or the various clinical–pathological variables, including Ki-67 and histologic grade, were identified. Finally, similar OS results were obtained in the CALGB data set, although the interaction test did not reach statistical significance (p = 0.109). The PAM50 proliferation score identifies a subset of patients with a low proliferation status that may derive a larger benefit from weekly paclitaxel. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10549-013-2416-2) contains supplementary material, which is available to authorized users

Evaluación de la resiliencia de sistemas ganaderos de pequeños rumiantes de razas locales en España

Los indicadores desarrollados para evaluar la resiliencia permiten encontrar diferencias entre los ca - sos de estudio, por lo que constituyen una herramienta útil para estudiar el estado actual de su resiliencia. Sin embargo, la resiliencia es variable debido a sus características propias, lo que significa que además de las particularidades de los sistemas en su conjunto, el uso de indicadores a nivel de explotación es fundamental para evaluar su resiliencia de forma individualizada y por tanto para enten der cuáles son los puntos débiles que se deben mejorar en ellas.Agradecimientos: A los ganaderos y ganaderas que han participado en las encuestas. Trabajo financiado por RUMIRES (Proyecto PID2020-120312RA-I00 financiada por MCIN/AEI/10.13039/501100011033) y por el Gobierno de Aragón (contrato para investigadores predoctorales 2021/2024)

Impacts of use and abuse of nature in Catalona with proposal for sustainable management

This paper provides an overview of the last 40 years of use, and in many cases abuse, of the natural resources in Catalonia, a country that is representative of European countries in general, and especially those in the Mediterranean region. It analyses the use of natural resources made by mining, agriculture, livestock, logging, fishing, nature tourism, and energy production and consumption. This use results in an ecological footprint, i.e., the productive land and sea surface required to generate the consumed resources and absorb the resulting waste, which is about seven times the amount available, a very high number but very similar to other European countries. This overexploitation of natural resources has a huge impact on land and its different forms of cover, air, and water. For the last 25 years, forests and urban areas have each gained almost 3% more of the territory at the expense of agricultural land; those municipalities bordering the sea have increased their number of inhabitants and activity, and although they only occupy 6.7% of the total surface area, they account for 43.3% of the population; air quality has stabilized since the turn of the century, and there has been some improvement in the state of aquatic ecosystems, but still only 36% are in good condition, while the remainder have suffered morphological changes and different forms of nonpoint source pollution; meanwhile the biodiversity of flora and fauna remains still under threat. Environmental policies do not go far enough so there is a need for revision of the legislation related to environmental impact and the protection of natural areas, flora, and fauna. The promotion of environmental research must be accompanied by environmental education to foster a society which is more knowledgeable, has more control and influence over the decisions that deeply affect it. Indeed, nature conservation goes hand in hand with other social and economic challenges that require a more sustainable vision. Today's problems with nature derive from the current economic model, which is environmentally unsustainable in that it does not take into account environmental impacts. Lastly, we propose a series of reasonable and feasible priority measures and actions related to each use made of the country's natural resources, to the impacts they have had, and to their management, in the hope that these can contribute to improving the conservation and management of the environment and biodiversity and move towards sustainability

Habitat quality affects the condition of Luciobarbus sclateri in the Guadiamar River (SW Iberian Peninsula): Effects of disturbances by the toxic spill of the Aznalcóllar mine

This study analyzes the somatic condition of southern Iberian barbel Luciobarbus sclateri (Günther, 1868) in the Guadiamar River (SW Iberian Peninsula). This river was seriously affected by a toxic spill of about 4 million cubic meters of acidic water and 2 million cubic meters of mud rich in heavy metals. Once the spill removal works concluded, sites affected and unaffected by the accident were sampled to study its effects on the fish fauna. The ecological variables registered were related to water quality, physical state of reaches, ecological quality, resources exploited by fish, and potential intra-specific interactions. From an initial 15 ecological variables, seasonal water flow and pH explained most of the variation in barbel condition. This study shows that the Guadiamar River, 56 months after the accident, is still undergoing a recovery process where, beyond ecological variables, proximity to the affected area is the most influential factor for fish condition. © 2012 Springer Science+Business Media B.V

Gibberellin A1 Metabolism Contributes to the Control of Photoperiod-Mediated Tuberization in Potato

Some potato species require a short-day (SD) photoperiod for tuberization, a process that is negatively affected by gibberellins (GAs). Here we report the isolation of StGA3ox2, a gene encoding a GA 3-oxidase, whose expression is increased in the aerial parts and is repressed in the stolons after transfer of photoperiod-dependent potato plants to SD conditions. Over-expression of StGA3ox2 under control of constitutive or leaf-specific promoters results in taller plants which, in contrast to StGA20ox1 over-expressers previously reported, tuberize earlier under SD conditions than the controls. By contrast, StGA3ox2 tuber-specific over-expression results in non-elongated plants with slightly delayed tuber induction. Together, our experiments support that StGA3ox2 expression and gibberellin metabolism significantly contribute to the tuberization time in strictly photoperiod-dependent potato plants

Dark Energy Survey: A 2.1% measurement of the angular Baryonic Acoustic Oscillation scale at redshift zeffz_{\rm eff}=0.85 from the final dataset

We present the angular diameter distance measurement obtained with the Baryonic Acoustic Oscillation feature from galaxy clustering in the completed Dark Energy Survey, consisting of six years (Y6) of observations. We use the Y6 BAO galaxy sample, optimized for BAO science in the redshift range 0.6<$z$<1.2, with an effective redshift at $z_{\rm eff}$=0.85 and split into six tomographic bins. The sample has nearly 16 million galaxies over 4,273 square degrees. Our consensus measurement constrains the ratio of the angular distance to sound horizon scale to $D_M(z_{\rm eff})/r_d$ = 19.51$\pm$0.41 (at 68.3% confidence interval), resulting from comparing the BAO position in our data to that predicted by Planck $\Lambda$CDM via the BAO shift parameter $\alpha=(D_M/r_d)/(D_M/r_d)_{\rm Planck}$. To achieve this, the BAO shift is measured with three different methods, Angular Correlation Function (ACF), Angular Power Spectrum (APS), and Projected Correlation Function (PCF) obtaining $\alpha=$ 0.952$\pm$0.023, 0.962$\pm$0.022, and 0.955$\pm$0.020, respectively, which we combine to $\alpha=$ 0.957$\pm$0.020, including systematic errors. When compared with the $\Lambda$CDM model that best fits Planck data, this measurement is found to be 4.3% and 2.1$\sigma$ below the angular BAO scale predicted. To date, it represents the most precise angular BAO measurement at $z$>0.75 from any survey and the most precise measurement at any redshift from photometric surveys. The analysis was performed blinded to the BAO position and it is shown to be robust against analysis choices, data removal, redshift calibrations and observational systematics.Comment: Submitted to PRD, 39 pages, 12 figure