Driven by technical advances and favorable regulatory measures (albeit only in some countries), the deployment of electricity generation at very small scales, or micro-generation, is shaping a new segment of the electricity system which has been called “Residential Energy Sector” or “Micro-Generation Sector”. Known as “self-production” or “self-consumption” years ago, the main objective of on-site, or demand-side, microgeneration is to provide electricity services to homes and businesses from their own plants. While the concept of avoided cost has been used in the past, a dynamic model which takes into account the different influencing factors has not been previously developed. This paper closes this gap in the literature. It proposes a dynamic, easily replicable model which contains the main factors which influence the avoided costs and facilitates the analysis of the investment decisions taken by residential prosumers. The results show that, compared to other variables, the evolution of retail prices is the most relevant factor affecting the avoided cost, suggesting that their gradual increase could lead to the substitution of plants before the end of their useful life. However, the importance of retail prices and their unknown evolution gives investment decisions on residential plants an inherent uncertain character. Therefore, a higher retail price can encourage the investment by reducing the recovery period. If the accumulated avoided cost equals the initial investment earlier, this reduces both the uncertainty (the period is shorter) and the psychological impact of a strong initial expense. Although regulatory factors (e.g., the existence of subsidies and the conditions of grid exchange) do not have a large economic impact, those factors contribute to the change in the psychological framework which future prosumers will face. In particular, they partly offset the detrimental impact of the initial upfront costs on the decision to invest, even if the revenues and other advantages offset such initial amount of investment.
- Eulogio Pleguezuelos
- Amin Del Carmen
- Eva Moreno
- Manuel V. Garnacho‐Castaño
Background This study aimed to evaluate the effects of a 15‐week telerehabilitation program and a detraining period on cardiorespiratory fitness and mechanical efficiency in patients with post‐COVID‐19 sequelae. Methods 131 patients with post‐COVID‐19 sequelae were randomly assigned to one of two groups: patients who carried out the supervised telerehabilitation program (TRG, n = 66) and a control group (CG, n = 65). An incremental cardiopulmonary exercise testing (CPET) was performed on cycle ergometer to compare cardioventilatory responses between experimental groups. Results A significant increase in the CPET duration, peak power output, and mechanical efficiency was observed in TRG compared to CG after the telerehabilitation program (p ≤ 0.001). A significant increase in the CPET duration, peak power output, and mechanical efficiency was verified at 3 months compared to the pretest and after detraining in TRG (p < 0.001). A significant increase in peak oxygen uptake (V̇O2peak) was identified after the intervention and in the detraining period compared to the pretest in both experimental groups (p < 0.001). A higher ventilatory efficiency was observed after the telerehabilitation program (p = 0.021) than in pretest only in TRG. Conclusions A 15‐week supervised home telerehabilitation program improved exercise capacity, power output, and mechanical efficiency in TRG compared to a CG. The telerehabilitation program was not more effective in improving V̇O2peak than the activities of the CG. However, ventilatory efficiency was improved only after the telerehabilitation program. The reported results after the detraining period highlight the need to maintain the rehabilitation program over time.
El consumo y la eventual evitación de noticias digitales muestra características diferenciales relacionadas con la desigualdad económica en España. Al tratarse de un sistema democrático polarizado, de acuerdo con la clasificación de Hallin y Mancini de 2004, España tiene algunos rasgos un tanto diferenciados de otros países de su entorno. De acuerdo con los datos obtenidos en una encuesta propia llevada a cabo en el primer trimestre de 2022, una cuarta parte de quienes respondieron -de forma convenientemente estratificada- aseguraron que tienen poca confianza en las noticias digitales de los medios de comunicación. De ellos, la mitad indica que la razón de evitar el consumo de noticias, al menos de forma directa -otra cosa es el consumo incidental- es la falta de credibilidad de los medios de comunicación, mayor incluso que la que atribuyen a los periodistas. Por otra parte, la clase social -es decir, los ingresos económicos, además de factores como la educación- influye en cómo se consumen las noticias. Las clases más desfavorecidas evitan más el acceso directo a los medios, pero, por razones diferentes; también lo hacen las clases altas, seguramente porque obtienen la información por otros conductos.
Aim The aim of this study was to investigate the clinical relevance of an isolated positive sonication fluid culture (SFC) in patients who underwent revision surgery of a prosthetic joint. We hypothesized that cases with a positive SFC have a higher rate of infection and prosthesis failure during follow-up compared to controls with a negative SFC. Method This retrospective multicentre observational study was performed within the European Study Group of Implant-Associated Infections (ESGIAI). All patients who underwent revision surgery of a prosthetic joint between 2013 and 2019 and had a minimum follow-up of 1 year were included. Patients with positive tissue cultures or synovial fluid cultures were excluded from the study. Results 95 cases (positive SFC) and 201 controls (negative SFC) were included. There was no difference in infection and prosthesis failure during follow-up between both groups. When solely analysing patients that were not treated with antibiotics, 16% of the cases had an infection during follow-up versus 5% of the controls (P 0.046). Conclusions Withholding antimicrobial treatment in patients with an isolated positive SFC is associated with a higher reinfection rate. Antimicrobial treatment should be considered in isolated positive SFC, especially in case of high virulent pathogens.
This study investigates whether the cognitive reappraisal strategy is influenced by the participant’s language (native/foreign) when confronting a fearful stimulus. Sixty participants with subclinical phobia of cockroaches were exposed to several phobic and neutral pictures while they used cognitive reappraisal in their native language or a foreign one. Electrodermal activity, pupil dilation, and self-reports of affective valence and arousal were collected. Results showed that participants in the foreign context were more effective at using reappraisal to reduce valence self-ratings compared to using no regulation. Also, participants in the foreign context showed greater pupil size when reappraising their emotions, compared to the non-regulation condition. Depending on the language, no differences were found for arousal self-reports or electrodermal activity when using reappraisal. These results suggest that using a foreign language could be advantageous in reducing the negative valence through reappraisal. Psychophysiological results are discussed in light of cognitive effort studies.
Archamoebae comprises free-living or endobiotic amoebiform protists that inhabit anaerobic or microaerophilic environments and possess mitochondrion-related organelles (MROs) adapted to function anaerobically. We compared in silico reconstructed MRO proteomes of eight species (six genera) and found that the common ancestor of Archamoebae possessed very few typical components of the protein translocation machinery, electron transport chain and tricarboxylic acid cycle. On the other hand, it contained a sulphate activation pathway and bacterial iron–sulphur (Fe-S) assembly system of MIS-type. The metabolic capacity of the MROs, however, varies markedly within this clade. The glycine cleavage system is widely conserved among Archamoebae, except in Entamoeba , probably owing to its role in catabolic function or one-carbon metabolism. MRO-based pyruvate metabolism was dispensed within subgroups Entamoebidae and Rhizomastixidae, whereas sulphate activation could have been lost in isolated cases of Rhizomastix libera , Mastigamoeba abducta and Endolimax sp. The MIS (Fe-S) assembly system was duplicated in the common ancestor of Mastigamoebidae and Pelomyxidae, and one of the copies took over Fe-S assembly in their MRO. In Entamoebidae and Rhizomastixidae, we hypothesize that Fe-S cluster assembly in both compartments may be facilitated by dual localization of the single system. We could not find evidence for changes in metabolic functions of the MRO in response to changes in habitat; it appears that such environmental drivers do not strongly affect MRO reduction in this group of eukaryotes.
The cultural and biological diversity of South American indigenous groups represent extremes of human variability, exhibiting one of the highest linguistic diversities alongside a remarkably low within‐population genetic variation and an extremely high inter‐population genetic differentiation. On top of that, this region has seen some of the most dramatic demographic events in human history unleashed by the European colonization of the Americas. As a result of this process, the distribution of indigenous populations has been radically changed. In this review we focus on the Tupi, the largest and most widespread linguistic family in eastern South America. Tupi are believed to have originated in southwestern Amazon, from where some of its subfamilies expanded into other parts of the Amazon and, in the case of the Tupi‐Guarani, beyond its borders. Recent evidence from archaeology, linguistics, and genetics aligns with José Brochado's Tupi Expansion model. He proposed that the gradual development of agricultural systems within the Amazon resulted in population growth and, eventually, territorial expansion. This model also supports separate Tupi Expansion branches: Tupinambá (Atlantic coast) and Guarani (south, midwest Brazil). Although being the most populous group on Brazil's Atlantic coast, which was the most affected by European colonization, the Tupi still account for roughly 20% of the country's overall indigenous population. Finally, despite its importance and more than a century of research on the Tupi and their expansion history, many key questions remain unanswered, which we attempt to summarize and explore here.
Background Galcanezumab has shown efficacy and effectiveness in the treatment of episodic and chronic migraine (CM), however, the population represented in randomized clinical trials (RCTs) differs from the population observed in real-world setting. To describe the long-term effectiveness and tolerability of galcanezumab in clinical practice in patients excluded from RCTs. Methods Multicenter prospective cohort study of consecutive patients with chronic and high-frequency episodic migraine (HFEM) with prior failure to three or more migraine preventive drugs, treated with galcanezumab and followed up for 12 months. Results We enrolled 1055 patients, aged 50 (IQR: 42–58), 82.9% female, 76.4% chronic migraine, 69% with at least one exclusion criteria for RCTs, including age > 65 (n = 121), concomitant use of onabotulinumtoxinA (n = 185), daily headache at baseline (n = 347), chronic painful syndromes (n = 206), fibromyalgia (n = 101) or treatment resistance (n = 957). The median number of prior preventive treatments was 4 (IQR: 3–5). The retention rate was 90.8%, 76.8% and 71.4% at 3, 6 and 12 months. The main reasons for treatment discontinuation were lack of effectiveness (21.1%) and inadequate tolerability (6.6%). The 30%, 50% and 75% responder rates were 62.6%, 49.8% and 24.2% between weeks 8–12; 60.9%, 48.8% and 24.6% between weeks 20–24; and 59.7%, 48.3% and 24.6% between weeks 44–48. Daily headache at baseline (OR: 0.619; 95%CI: 0.469–0.817) and patient’s age (OR: 1.016; 95%CI: 1.005–1.026) were associated with 50% response at weeks 20–24. The variables that were associated with a higher reduction of headache days between weeks 20–24 were patient’s age (0.068; 95% CI: 0.018–0.119) and headache days per month at baseline (0.451; 95% CI: 0.319–0.583), while psychiatric comorbidity (-1.587; 95% CI: -2.626—0.538) and daily headache at baseline (-2.718; 95% CI: -4.58—0.869) were associated with fewer reduction in the number of headache days between weeks 20–24. Conclusion This study provides class III evidence of effectiveness and tolerability of galcanezumab in patients with HFEM and CM with comorbidities that would result in exclusion of the pivotal RCTs. Nonetheless, the clinical results over a 12-month period were similar to the efficacy observed in randomized controlled trials. Few patients discontinued the drug due to inadequate tolerability.
Chronic urticaria (CU) is the recurring development of wheals (aka “hives” or “welts”), angioedema, or both for more than 6 weeks. Wheals and angioedema occur with no definite triggers in chronic spontaneous urticaria, and in response to known and definite physical triggers in chronic inducible urticaria. Approximately 1.4% of individuals globally will have CU during their lifetime. The itching and physical discomfort associated with CU have a profound impact on daily activities, sexual function, work or school performance, and sleep, causing significant impairment in a patient’s physical and mental quality of life. CU also places a financial burden on patients and healthcare systems. Patients should feel empowered to self-advocate to receive the best care. The voice of the patient in navigating the journey of CU diagnosis and management may improve patient–provider communication, thereby improving diagnosis and outcomes. A collaboration of patients, providers, advocacy organizations, and pharmaceutical representatives have created a patient charter to define the realistic and achievable principles of care that patients with CU should expect to receive. Principle (1): I deserve an accurate and timely diagnosis of my CU; Principle (2): I deserve access to specialty care for my CU; Principle (3): I deserve access to innovative treatments that reduce the burden of CU on my daily life; Principle (4): I deserve to be free of unnecessary treatment-related side-effects during the management of my CU; and Principle (5): I expect a holistic treatment approach to address all the components of my life impacted by CU. The stated principles may serve as a guide for healthcare providers who care for patients with CU and translate into better patient–physician communication. In addition, we urge policymakers and authors of CU treatment guidelines to consider these principles in their decision-making to ensure the goals of the patient are achievable.
Chromosome segregation relies on the correct assembly of a bipolar spindle. Spindle pole self-organization requires dynein-dependent microtubule transport along other microtubules. However, during M-phase RanGTP triggers microtubule nucleation and branching generating polarized arrays with non-astral organization in which microtubule minus ends are linked to the sides of other microtubules. This raises the question of how branched-microtubule nucleation and dynein-mediated transport cooperate to organize the spindle poles. Here, we used RanGTP-dependent microtubule aster formation in Xenopus laevis egg extract to study the interplay between these two seemingly conflicting organizing principles. Using temporally controlled perturbations of microtubule nucleation and dynein activity, we found that branched microtubules are not static but instead dynamically redistribute over time as poles self-organize. Our experimental data together with computer simulations suggest a model where dynein together with dynactin and NuMA directly pulls and move branched microtubule minus ends towards other microtubule minus ends.
Individuals with Down syndrome (DS) have a higher prevalence of obesity compared to the general population. Conventionally, this has been attributed to endocrine issues and lack of exercise. However, deficits in neural reward responses and dopaminergic disturbances in DS may be contributing factors. To investigate this, we focused on a mouse model (Ts65Dn) bearing some triplicated genes homologous to trisomy 21. Through detailed meal pattern analysis in male Ts65Dn mice, we observed an increased preference for energy-dense food, pointing towards a potential “hedonic” overeating behavior. Moreover, trisomic mice exhibited higher scores in compulsivity and inflexibility tests when limited access to energy-dense food and quinine hydrochloride adulteration were introduced, compared to euploid controls. Interestingly, when we activated prelimbic-to-nucleus accumbens projections in Ts65Dn male mice using a chemogenetic approach, impulsive and compulsive behaviors significantly decreased, shedding light on a promising intervention avenue. Our findings uncover a novel mechanism behind the vulnerability to overeating and offer potential new pathways for tackling obesity through innovative interventions.
Background: Accumulation of amyloid-β (Aβ) plaques is one of the main features of Alzheimer’s disease (AD). Physical performance has been related to dementia risk and Aβ, and it has been hypothesized as one of the mechanisms leading to greater accumulation of Aβ. Yet, no evidence synthesis has been performed in humans. Objective: To investigate the association of physical performance with Aβ in humans, including Aβ accumulation on brain, and Aβ abnormalities measured in cerebrospinal fluid (CSF) and blood. Methods: A systematic review with multilevel meta-analysis was performed from inception to June 16th, 2022. Studies were eligible if they examined the association of physical performance with Aβ levels, including the measure of physical performance as a predictor and the measure of Aβ as an outcome in humans. Results: 7 articles including 2,619 participants were included in the meta-analysis. The results showed that physical performance was not associated with accumulation of Aβ in the brain (ES = 0.01; 95% CI –0.21 to 0.24; I2 = 69.9%), in the CSF (ES = –0.28; 95% CI –0.98 to 0.41; I2 = 91.0%) or in the blood (ES = –0.19; 95% CI –0.61 to 0.24; I2 = 99.75%). Significant heterogeneity was found across the results , which posed challenges in arriving at consistent conclusions; and the limited number of studies hindered the opportunity to conduct a moderation analysis. Conclusions: The association between physical performance and Aβ is inconclusive. This uncertainly arises from the limited number of studies, study design limitations, and heterogeneity of measurement approaches. More studies are needed to determine whether physical performance is related to Aβ levels in humans.
The frontal pole is implicated in humans in whether to exploit resources versus explore alternatives. Effective connectivity, functional connectivity, and tractography were measured between six human frontal pole regions and for comparison 13 dorsolateral and dorsal prefrontal cortex regions, and the 360 cortical regions in the Human Connectome Project Multi-modal-parcellation atlas in 171 HCP participants. The frontal pole regions have effective connectivity with Dorsolateral Prefrontal Cortex regions, the Dorsal Prefrontal Cortex, both implicated in working memory; and with the orbitofrontal and anterior cingulate cortex reward/non-reward system. There is also connectivity with temporal lobe, inferior parietal, and posterior cingulate regions. Given this new connectivity evidence, and evidence from activations and damage, it is proposed that the frontal pole cortex contains autoassociation attractor networks that are normally stable in a short-term memory state, and maintain stability in the other prefrontal networks during stable exploitation of goals and strategies. However, if an input from the orbitofrontal or anterior cingulate cortex that expected reward, non-reward, or punishment is received, this destabilizes the frontal pole and thereby other prefrontal networks to enable exploration of competing alternative goals and strategies. The frontal pole connectivity with reward systems may be key in exploit versus explore.
Faced with the inaction of liberal democracies to effectively tackle global warming, many climate activists engage in forms of protests that involve committing minor criminal offences. They seek to shape official decisions on climate policies by resorting to civil disobedience. Some of these activists, rather than accepting punishment, have successfully claimed to be acting in a justified manner by invoking the necessity defence. The aim of this article is to show that, within the framework of representative democracies guided by the rule of law, the climate necessity defence must be rejected, since such protests do not meet the 'non-legal alternatives' requirement. This does not mean, however, that protesters should be punished as common offenders. Their acceptance of responsibility and political motivation should be taken into account as a mitigating factor at sentencing.
We study whether and how governments influence public opinion about immigration policies in Europe. At the European level, conflicts about policy are generally territorial in nature – that is, they involve conflicts between member states, which are represented by their governments. Distinguishing between four types of situations, depending on whether the national governments support or oppose EU policy proposals, we formulate and test hypotheses concerning the positions of incumbent and opposition voters/non-voters on four different asylum-policy proposals in 16 European countries. We test both direct effects of incumbent cues on voters' preferences, and moderating effects, where the cueing affects the way in which individual attitudes to immigration and European integration translate into specific preferences for EU asylum and immigration policies. Our results suggest that voters, indeed, follow the cues provided by their governments when forming their preferences on EU policies.
The prevalence of post-COVID-19 condition is not well defined. We describe a cohort of 244 children diagnosed with COVID-19 and followed up for 6 months, in which 4.9% of patients had persistent symptoms at 12 weeks. Anosmia was the most frequent symptom. Being female and having more than 3 symptoms in acute infection were associated with an increased risk of post-COVID.
Phenotypic variation is the phenomenon in which clonal cells display different traits even under identical environmental conditions. This plasticity is thought to be important for processes including bacterial virulence, but direct evidence for its relevance is often lacking. For instance, variation in capsule production in the human pathogen Streptococcus pneumoniae has been linked to different clinical outcomes, but the exact relationship between variation and pathogenesis is not well understood due to complex natural regulation. In this study, we use synthetic oscillatory gene regulatory networks (GRNs) based on CRISPR interference (CRISPRi) together with live cell imaging and cell tracking within microfluidics devices to mimic and test the biological function of bacterial phenotypic variation. We provide a universally applicable approach for engineering intricate GRNs using only two components: dCas9 and extended sgRNAs (ext-sgRNAs). Our findings demonstrate that variation in capsule production is beneficial for pneumococcal fitness in traits associated with pathogenesis providing conclusive evidence for this longstanding question.
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