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PROVIDER: S-EPMC1954724 | biostudies-literature | 2007 Aug
REPOSITORIES: biostudies-literature
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Project description:Humans can estimate confidence in their decisions, and there is increasing interest on how this feeling of confidence regulates future behavior. Here, we investigate whether confidence in a perceptual task affects prioritizing future trials of that task, independently of task performance. To do so, we experimentally dissociated confidence from performance. Participants judged whether an array of differently colored circles was closer to blue or red, and we manipulated the mean and variability of the circles' colors across the array. We first familiarized participants with a low mean low variability condition and a high mean high variability condition, which were matched in performance despite participants being more confident in the former. Then we made participants decide in which order to complete forthcoming trials for both conditions. Crucially, prioritizing one condition was associated with being more confident in that condition compared to the other. This relationship was observed both across participants, by correlating inter-individual heterogeneity in prioritization and in confidence, and within participants, by assessing how changes in confidence with accuracy, condition and response times could predict prioritization choices. Our results suggest that confidence, above and beyond performance, guides prioritization between forthcoming tasks, strengthening the evidence for its role in regulating behavior.
| S-EPMC8443637 | biostudies-literature
Project description:Concealing information requires that adolescents manage the information that they share, which requires cognitive skills, for example, theory of mind (ToM). This study explored motivations for concealment that early adolescents (N = 90, M = 12.81 years, SD = 5.10 months, range 12-14 years, and 58% female) endorsed concealing or disclosing to friends and parents, in relation to their theory of mind. We found that adolescents broadly endorsed disclosure to both parents and friends, even when it might mean they would face consequences, be impolite (by not protecting another's feelings), or face negative identity-related emotions. We found that ToM ability was associated with a tendency to endorse being forthcoming and sharing information with both friends and parents. These findings provide new insight into how the relation between ToM and concealment may change with age, specifically how in early adolescence it may foster open communication rather than concealment as is the case in early and middle childhood.
| S-EPMC9046603 | biostudies-literature
Project description:Opioids represent an efficacious therapeutic modality for some, but not all pain states. Singular reliance on opioid therapy for pain management has limitations, and abuse potential has deleterious consequences for patient and society. Our understanding of pain biology has yielded insights and opportunities for alternatives to conventional opioid agonists. The aim is to have efficacious therapies, with acceptable side effect profiles and minimal abuse potential, which is to say an absence of reinforcing activity in the absence of a pain state. The present work provides a nonexclusive overview of current drug targets and potential future directions of research and development. We discuss channel activators and blockers, including sodium channel blockers, potassium channel activators, and calcium channel blockers; glutamate receptor-targeted agents, including N-methyl-D-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, and metabotropic receptors. Furthermore, we discuss therapeutics targeted at γ-aminobutyric acid, α2-adrenergic, and opioid receptors. We also considered antagonists of angiotensin 2 and Toll receptors and agonists/antagonists of adenosine, purine receptors, and cannabinoids. Novel targets considered are those focusing on lipid mediators and anti-inflammatory cytokines. Of interest is development of novel targeting strategies, which produce long-term alterations in pain signaling, including viral transfection and toxins. We consider issues in the development of druggable molecules, including preclinical screening. While there are examples of successful translation, mechanistically promising preclinical candidates may unexpectedly fail during clinical trials because the preclinical models may not recapitulate the particular human pain condition being addressed. Molecular target characterization can diminish the disconnect between preclinical and humans' targets, which should assist in developing nonaddictive analgesics.
| S-EPMC5679134 | biostudies-literature
Project description: Not available
| S-EPMC8986455 | biostudies-literature
Project description:The Atlantic meridional overturning circulation (AMOC) is a major tipping element in the climate system and a future collapse would have severe impacts on the climate in the North Atlantic region. In recent years weakening in circulation has been reported, but assessments by the Intergovernmental Panel on Climate Change (IPCC), based on the Climate Model Intercomparison Project (CMIP) model simulations suggest that a full collapse is unlikely within the 21st century. Tipping to an undesired state in the climate is, however, a growing concern with increasing greenhouse gas concentrations. Predictions based on observations rely on detecting early-warning signals, primarily an increase in variance (loss of resilience) and increased autocorrelation (critical slowing down), which have recently been reported for the AMOC. Here we provide statistical significance and data-driven estimators for the time of tipping. We estimate a collapse of the AMOC to occur around mid-century under the current scenario of future emissions.
| S-EPMC10368695 | biostudies-literature
Project description:Recent bursts in the incidence of large wildfires worldwide have raised concerns about the influence climate change and humans might have on future fire activity. Comparatively little is known, however, about the relative importance of these factors in shaping global fire history. Here we use fire and climate modeling, combined with land cover and population estimates, to gain a better understanding of the forces driving global fire trends. Our model successfully reproduces global fire activity record over the last millennium and reveals distinct regimes in global fire behavior. We find that during the preindustrial period, the global fire regime was strongly driven by precipitation (rather than temperature), shifting to an anthropogenic-driven regime with the Industrial Revolution. Our future projections indicate an impending shift to a temperature-driven global fire regime in the 21st century, creating an unprecedentedly fire-prone environment. These results suggest a possibility that in the future climate will play a considerably stronger role in driving global fire trends, outweighing direct human influence on fire (both ignition and suppression), a reversal from the situation during the last two centuries.
| S-EPMC2984177 | biostudies-literature
Project description:Ongoing fluctuations of intrinsic cortical networks determine the dynamic state of the brain, and influence the perception of forthcoming sensory inputs. The functional state of these networks is defined by the amplitude and phase of ongoing oscillations of neuronal populations at different frequencies. The contribution of functionally different cortical networks has yet to be elucidated, and only a clear dependence of sensory perception on prestimulus alpha oscillations has been clearly identified. Here, we combined electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) in a large sample of healthy participants to investigate how ongoing fluctuations in the activity of different cortical networks affect the perception of subsequent nociceptive stimuli. We observed that prestimulus EEG oscillations in the alpha (at bilateral central regions) and gamma (at parietal regions) bands negatively modulated the perception of subsequent stimuli. Combining information about alpha and gamma oscillations predicted subsequent perception significantly more accurately than either measure alone. In a parallel experiment, we found that prestimulus fMRI activity also modulated the perception of subsequent stimuli: perceptual ratings were higher when the BOLD signal was higher in nodes of the sensorimotor network and lower in nodes of the default mode network. Similar to what observed in the EEG data, prediction accuracy was improved when the amplitude of prestimulus BOLD signals in both networks was combined. These findings provide a comprehensive physiological basis to the idea that dynamic changes in brain state determine forthcoming behavioral outcomes. Hum Brain Mapp 37:501-514, 2016. © 2015 Wiley Periodicals, Inc.
| S-EPMC4843944 | biostudies-literature
Project description:BackgroundGlioblastoma multiforme is a CNS cancer characterized by diffuse infiltrative growth, aggressive clinical behavior and very poor prognosis. The state-of-art clinical approach to this disease consists of surgical resection followed by radiotherapy plus concurrent and adjuvant chemotherapy with temozolomide. Tumor recurrence occurs in virtually all cases, therefore, despite any treatment, the median survival is very low (14.6 months), which makes the approach to these patients a challenging clinical issue.Main bodyThe escalating costs and times required for new medications to reach the bedside make repurposing or repositioning of old drugs, when scientific bases allow their use in other pathologies, an appealing strategy. Here, we analyze a number of literature data concerning the antipsychotic chlorpromazine, the founder of the phenothiazines class of drugs, a medication widely used in the clinics for approximately 60 years. The drug exerts its effects on psychiatric patients by interfering with the dopamine receptor D2, although more recent pharmacodynamics studies ascribe chlorpromazine a series of biological effects on cancer cells, all converging in hindering also glioblastoma survival capabilities.Short conclusionsOn these bases, and assisted by the information on the well-established chlorpromazine toxicity and dosage in humans, we designed a Phase II clinical trial involving the combination of chlorpromazine with the standard treatment, temozolomide, in the adjuvant phase of the therapeutic protocol. Patients displaying hypo-methylation of the MGMT gene, and thus intrinsically resistant to temozolomide, will be enrolled. The endpoints of this study are the analysis of toxicity and clinical activity, as evaluated in terms of Progression-Free Survival, of the association of chlorpromazine with the first-line treatment for this very serious form of cancer.
| S-EPMC6995164 | biostudies-literature
Project description:The outcome of patients with relapsed/refractory classical Hodgkin lymphoma (rr-cHL) has improved considerably in recent years owing to the approval of highly active novel agents such as brentuximab vedotin and Programmed Death-1 (PD-1) inhibitors. Although no randomized trials have been conducted to provide formal proof, it is almost undisputable that the survival of these patients has been prolonged. As autologous stem-cell transplantation (SCT) remains the standard of care for second-line therapy of most patients with rr-cHL, optimization of second-line regimens with the use of brentuximab vedotin, or, in the future, checkpoint inhibitors, is promising to increase both the eligibility rate for transplant and the final outcome. The need for subsequent therapy, and especially allogeneic SCT, can be reduced with brentuximab vedotin consolidation for 1?year, while pembrolizumab is also being tested in this setting. Several other drug categories appear to be active in rr-cHL, but their development has been delayed by the appearance of brentuximab vedotin, nivolumab and pembrolizumab, which have dominated the field of rr-cHL treatment in the last 5?years. Combinations of active drugs in chemo-free approaches may further increase efficacy and hopefully reduce toxicity in rr-cHL, but are still under development.
| S-EPMC7026824 | biostudies-literature
Project description:BackgroundCognitive changes in Huntington's disease (HD) precede motor manifestations. ENROLL-HD platform includes four cognitive measures of information processing speed (IPS). Our group is eager to seek clinical markers in the life stage that is as close as possible to the age of onset (ie, the so called prodromal HD phase) because this is the best time for therapeutic interventions.ObjectivesOur study aimed to test whether cognitive scores in prodromal ENROLL-HD mutation carriers show the potential to predict the severity of motor and behavioral changes once HD became fully manifested.MethodsFrom the global ENROLL-HD cohort of 21,343 participants, we first selected a premanifest Cohort#1 (ie, subjects with Total Motor Score (TMS) <10 and Diagnostic Confidence Level (DCL) <4, N = 1.222). From this cohort, we then focused on a prodromal Cohort#2 of subjects who were ascertained to phenoconvert into manifest HD at follow-up visits (ie, subjects from 6 ≤ TMS≤9 and DCL <4 to TMS≥10 and DCL = 4, n = 206).ResultsThe main results of our study showed that low IPS before phenoconversion in Cohort#2 predicted the severity of motor and behavioral manifestations. By combining the four IPS cognitive measures (eg, the Categorical Verbal Fluency Test; Stroop Color Naming Test; Stroop Word Reading; Symbol Digit Modalities Test), we generated a Composite Cognition Score (CCS). The lower the CCS score the higher the TMS and the apathy scores in the same longitudinally followed-up patients after phenoconversion.ConclusionsCCS might represent a clinical instrument to predict the prognosis of mutation carriers who are close to manifesting HD.
| S-EPMC10982604 | biostudies-literature