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The effects of climate change depend on specific local circumstances, posing a challenge for worldwide research to comprehensively encompass the diverse impacts on various local social-ecological systems. Here we use a place-specific but cross-culturally comparable protocol to document climate change indicators and impacts as locally experienced and analyze their distribution. We collected first-hand data in 48 sites inhabited by Indigenous Peoples and local communities and covering all climate zones and nature-dependent livelihoods. We documented 1,661 site-agreed reports of change corresponding to 369 indicators. Reports of change vary according to climate zone and livelihood activity. We provide compelling evidence that climate change impacts on Indigenous Peoples and local communities are ongoing, tangible, widespread, and affect multiple elements of their social-ecological systems. Beyond potentially informing contextualized adaptation plans, our results show that local reports could help identify economic and non-economic loss and damage related to climate change impacts suffered by Indigenous Peoples and local communities.

Global polls have shown that people in high-income countries generally report being more satisfied with their lives than people in low-income countries. The persistence of this correlation, and its similarity to correlations between income and life satisfaction within countries, could lead to the impression that high levels of life satisfaction can only be achieved in wealthy societies. However, global polls have typically overlooked small-scale, nonindustrialized societies, which can provide an alternative test of the consistency of this relationship. Here, we present results from a survey of 2,966 members of Indigenous Peoples and local communities among 19 globally distributed sites. We find that high average levels of life satisfaction, comparable to those of wealthy countries, are reported for numerous populations that have very low monetary incomes. Our results are consistent with the notion that human societies can support very satisfying lives for their members without necessarily requiring high degrees of monetary wealth.

Introduction In the quest to improve the understanding of climate change impacts on elements of the atmospheric, physical, and life systems, scientists are challenged by the scarcity and uneven distribution of grounded data. Through their long history of interaction with the environment, Indigenous Peoples and local communities have developed complex knowledge systems that allow them to detect impacts of climate change in the local environment. The study protocol presented here is designed 1) to inventory climate change impacts on the atmospheric, physical, and life systems based on local knowledge and 2) to test hypotheses on the global spatial, socioeconomic, and demographic distribution of reported impacts. The protocol has been developed within the framework of a project aiming to bring insights from Indigenous and local knowledge systems to climate research (https://licci.eu). Methods Data collection uses a mixed-method approach and relies on the collaboration of a team of 50 trained partners working in sites where people’s livelihood directly depend on nature. The data collection protocol consists of two steps. Step 1 includes the collection of secondary data (e.g., spatial and meteorological data) and site contextual information (e.g., village infrastructure, services). Step 1 also includes the use of 1) semi-structured interviews (n = 20-30/site) to document observations of environmental change and their drivers and 2) focus group discussions to identify consensus in the information gathered. Step 2 consist in the application of a household (n from 75 to 125) and individual survey (n from 125 to 175) using a standardized but locally adapted instrument. The survey includes information on 1) individual and household socio-demographic characteristics, 2) direct dependence on nature, 3) household’s vulnerability, and 4) individual perceptions of climate change impacts. Survey data are entered in a specifically designed database. Expected results This protocol al

L’objectiu d’aquest Treball de Final de Grau és investigar com és el perfil dels seguidors del futbol femení, sobretot en l’àmbit digital; i també l’impacte de les xarxes socials i la comunicació en els clubs de futbol femení d’Espanya i en les jugadores professionals. En aquest treball es fa una recerca teòrica per posar en context tot l’estudi, seguidament es fa una anàlisi dels seguidors del futbol femení i també de la comunicació dels clubs de futbol i l’ús de les xarxes socials, finalment s’avalua un cas d’èxit actual: Alexia Putellas, i finalment, s’extreuen les conclusions de la investigació tenint en compte tota la informació processada., The aim of this Final Degree Thesis is to investigate the profile of the followers of women's football, especially in the digital environment; and also the impact of social networks and communication in women's football clubs in Spain and in professional players. In this work, a theoretical research is carried out to put the whole study into context, followed by an analysis of the followers of women's football and also of the communication of football clubs and the use of social xarxes, finally, a current successful case is evaluated: Alexia Putellas, and finally, the conclusions of the research are drawn, taking into account all the information processed.

Introduction: In the quest to improve the understanding of climate change impacts on elements of the atmospheric, physical, and life systems, scientists are challenged by the scarcity and uneven distribution of grounded data. Through their long history of interaction with the environment, Indigenous Peoples and local communities have developed complex knowledge systems that allow them to detect impacts of climate change in the local environment. The study protocol presented here is designed 1) to inventory climate change impacts on the atmospheric, physical, and life systems based on local knowledge and 2) to test hypotheses on the global spatial, socioeconomic, and demographic distribution of reported impacts. The protocol has been developed within the framework of a project aiming to bring insights from Indigenous and local knowledge systems to climate research (https://licci.eu). Methods: Data collection uses a mixed-method approach and relies on the collaboration of a team of 50 trained partners working in sites where people's livelihood directly depend on nature. The data collection protocol consists of two steps. Step 1 includes the collection of secondary data (e.g., spatial and meteorological data) and site contextual information (e.g., village infrastructure, services). Step 1 also includes the use of 1) semi-structured interviews (n = 20-30/site) to document observations of environmental change and their drivers and 2) focus group discussions to identify consensus in the information gathered. Step 2 consist in the application of a household (n from 75 to 125) and individual survey (n from 125 to 175) using a standardized but locally adapted instrument. The survey includes information on 1) individual and household socio-demographic characteristics, 2) direct dependence on nature, 3) household's vulnerability, and 4) individual perceptions of climate change impacts. Survey data are entered in a specifically designed database. Expected results: This protocol

Background:Niemann-Pick disease Type C (NPC) is a genetic, incurable, neurodegenerative disorder. This orphan disease is most frequently caused by mutations in the NPC1 protein, resulting in intralysossomal cholesterol accumulation. NPC1 is found in neuronal cell bodies, axon terminals and synaptosomes, suggesting it plays a role in lysosomal degradation pathway and in synaptic transmission. Neuronal function is especially vulnerable to NPC1 deficiency and synaptic changes seem a key element in disease development. Currently, Miglustat (Zavesca (R)) is the only approved treatment for NPC. However, preclinical evidence showed that low-dose Efavirenz reverted synaptic defects through pharmacological activation of the enzyme CYP46. Methods:This is a single-center, phase II clinical trial to evaluate the efficacy and safety of Efavirenz in addition to standard of care in patients diagnosed with adult or late juvenile-onset NPC with cognitive impairment. All enrolled patients will be treated orally with 25 mg/d of Efavirenz for 52 weeks (1 year). Secondary objectives include evaluating clinical (neurological and neuropsychological questionnaires) and biological (imaging and biochemical biomarkers) parameters. Discussion:NPC is still an unmet medical need. Although different therapeutic approaches are under study, this is the first clinical trial (to the best of our knowledge) studying the effects of Efavirenz in adult- and late-juvenile-onset NPC. Despite the small sample size and the single-arm design, we expect the results to show Efavirenz's capacity of activating the CYP46 enzyme to compensate for NPC1 deficiency and correct synaptic changes, therefore compensating cognitive and psychiatric changes in these patients. This study may provide direct benefit to enrolled patients in terms of slowing down the disease progression.

[Background] Niemann-Pick disease Type C (NPC) is a genetic, incurable, neurodegenerative disorder. This orphan disease is most frequently caused by mutations in the NPC1 protein, resulting in intralysossomal cholesterol accumulation. NPC1 is found in neuronal cell bodies, axon terminals and synaptosomes, suggesting it plays a role in lysosomal degradation pathway and in synaptic transmission. Neuronal function is especially vulnerable to NPC1 deficiency and synaptic changes seem a key element in disease development. Currently, Miglustat (Zavesca®) is the only approved treatment for NPC. However, preclinical evidence showed that low-dose Efavirenz reverted synaptic defects through pharmacological activation of the enzyme CYP46., [Methods] This is a single-center, phase II clinical trial to evaluate the efficacy and safety of Efavirenz in addition to standard of care in patients diagnosed with adult or late juvenile-onset NPC with cognitive impairment. All enrolled patients will be treated orally with 25 mg/d of Efavirenz for 52 weeks (1 year). Secondary objectives include evaluating clinical (neurological and neuropsychological questionnaires) and biological (imaging and biochemical biomarkers) parameters., [Discussion] NPC is still an unmet medical need. Although different therapeutic approaches are under study, this is the first clinical trial (to the best of our knowledge) studying the effects of Efavirenz in adult- and late-juvenile-onset NPC. Despite the small sample size and the single-arm design, we expect the results to show Efavirenz’s capacity of activating the CYP46 enzyme to compensate for NPC1 deficiency and correct synaptic changes, therefore compensating cognitive and psychiatric changes in these patients. This study may provide direct benefit to enrolled patients in terms of slowing down the disease progression.

Altres ajuts: Acord transformatiu CRUE-CSIC, Data on the effectiveness and safety of a drug in real-world clinical practice complement the evidence from clinical trials, which are carried out in a different setting. Little has been published on the effectiveness and safety of guselkumab in the treatment of psoriasis in clinical practice. The ojective of this study was to assess the effectiveness and safety of guselkumab at 24 weeks in patients with moderate to severe plaque psoriasis in routine clinical practice. A retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis treated with guselkumab for at least 24 weeks was carried out in Spain. We studied 343 patients, 249 of whom were followed for 24 weeks. By week 24, the mean (SD) psoriasis area severity index (PASI) had decreased from 11.1 (7.3) to 1.7 (2.8) (−9.3; [−10.2;-8.4]), 85.9% of the patients had achieved PASI score of 4 or less and 77.9% a PASI score of 2 or less. In terms of relative PASI response, 59.4% of the patients achieved a PASI-90 response and 49.0% a PASI-100 response. On multivariate analysis, two factors reduced the probability of a PASI of 2 or less at 24 weeks: a BMI ≥30 (OR, 0.44; 95% CI, 0.22-0.88) and a greater previous exposure to biologic therapy (OR, 0.69; 95% CI, [0.56-0.84]). Adverse events were rare (9.9%) and led to withdrawal from treatment in only nine patients (2.6%) by the end of the follow-up period. The results of this study confirm the high efficacy and safety of guselkumab indicated by the clinical trial data. In clinical practice, the absolute PASI score appears to be a better marker of response to treatment than the relative value.

[Background] We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis., [Methods] A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy., [Results] Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93–1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018)., [Conclusions] Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events., [Clinical Trials Registration] NCT01898338.