A Large N400 but No BOLD Effect – Comparing Source Activations of Semantic Priming in Simultaneous EEG-fMRI

Numerous studies have reported neurophysiological effects of semantic priming in electroencephalography (EEG) and in functional magnetic resonance imaging (fMRI). Because of differing methodological constraints, the comparability of the observed effects remains unclear. To directly compare EEG and fMRI effects and neural sources of semantic priming, we conducted a semantic word-picture priming experiment while measuring EEG and fMRI simultaneously. The visually presented primes were pseudowords, words unrelated to the target, semantically related words and the identical names of the target. Distributed source analysis of the event-related potentials (ERPs) successfully revealed a large effect of semantic prime-target relatedness (the N400 effect), which was driven by activations in a left-temporal source region. However, no significantly differing activations between priming conditions were found in the fMRI data. Our results support the notion that, for joint interpretations of existing EEG and fMRI studies of semantic priming, we need to fully appreciate the respective methodological limitations. Second, they show that simultaneous EEG-fMRI, including ERP source localization, is a feasible and promising methodological advancement for the investigation of higher-cognitive processes. Third, they substantiate the finding that, compared to fMRI, ERPs are often more sensitive to subtle cognitive effects

Processing multiple non-adjacent dependencies: evidence from sequence learning

Processing non-adjacent dependencies is considered to be one of the hallmarks of human language. Assuming that sequence-learning tasks provide a useful way to tap natural-language-processing mechanisms, we cross-modally combined serial reaction time and artificial-grammar learning paradigms to investigate the processing of multiple nested (A(1)A(2)A(3)B(3)B(2)B(1)) and crossed dependencies (A(1)A(2)A(3)B(1)B(2)B(3)), containing either three or two dependencies. Both reaction times and prediction errors highlighted problems with processing the middle dependency in nested structures (A(1)A(2)A(3)B(3-)B(1)), reminiscent of the 'missing-verb effect' observed in English and French, but not with crossed structures (A(1)A(2)A(3)B(1-)B(3)). Prior linguistic experience did not play a major role: native speakers of German and Dutch-which permit nested and crossed dependencies, respectively-showed a similar pattern of results for sequences with three dependencies. As for sequences with two dependencies, reaction times and prediction errors were similar for both nested and crossed dependencies. The results suggest that constraints on the processing of multiple non-adjacent dependencies are determined by the specific ordering of the non-adjacent dependencies (i.e. nested or crossed), as well as the number of non-adjacent dependencies to be resolved (i. e. two or three). Furthermore, these constraints may not be specific to language but instead derive from limitations on structured sequence learning.Netherlands Organisation of Scientific Research (NWO) [446-08-014]; Max Planck Institute for Psycholinguistics; Donders Institute for Brain, Cognition and Behaviour; Fundacao para a Ciencia e Tecnologia (IBB/CBME, LA, FEDER/POCI) [PTDC/PSI-PCO/110734/2009]; Stockholm Brain Institute; Vetenskapsradet; Swedish Dyslexia Foundation; Hedlunds Stiftelse; Stockholm County Council (ALF, FoUU)info:eu-repo/semantics/publishedVersio

Evaluating coastal multifunctionality: sand nourishment strategies at decadal timescales

Globally, there is a growing societal need for multifunctional coastal climate adaptation of sandy shores in the coming decades. Sand nourishment strategies are increasingly regarded as promising nature-based approaches, as they may increase flood safety and mitigate erosion while enhancing recreational and ecological functioning. However, their multifunctional potential has not yet been assessed under diverse climate impacts at decadal scales. This study aimed to identify the effects of beach, shoreface and mega-nourishment strategies on coastal multifunctionality using a systems-based approach. We identified indicators for recreational, ecological and flood safety functions through a structured literature review, and integrated these into a process-based sand distribution model for dissipative coastal profiles. We simulated indicator states as the coastal profile responded to the nourishment strategies under five sea level rise scenarios and three erosion rates, and calculated the extent to which coastal functions and multifunctionality were supplied over six decades. We found that all three nourishment strategies could supply coastal multifunctionality to a high extent, although the drivers of this potential differed per strategy. These findings imply that sand nourishment strategies are viable approaches for multifunctional coastal climate adaption in the coming decades, that require prioritising specific coastal features and functions. While sand nourishment strategies remain high-impact interventions, they also allow for creating coastal landscapes that may not only prevent floods but also enhance the environmental and societal functions and features we desire of sandy shores worldwide.NWO17595Environmental Biolog

Health-related quality of life of patients with metastatic melanoma treated with tumor-infiltrating lymphocytes compared with ipilimumab in a randomized phase III trial

Background: This study aimed to assess health-related quality of life (HRQoL) in patients with metastatic melanoma treated with a tumor-infiltrating lymphocyte investigational medicinal product (TIL-IMP) or ipilimumab (IPI) after failure of first- or second-line treatment. Patients and methods: In a multicenter, randomized, phase III trial, patients with metastatic melanoma (unresectable stage IIIC-IV) were randomized to TIL-IMP or IPI treatment (NCT02278887). HRQoL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care (EORTC QLQ-C15-PAL), EuroQol 5D-3L (EQ-5D), and the Impact of Event Scale (IES). HRQoL outcomes were evaluated using a generalized estimating equations model. Sensitivity analyses were carried out to assess dropout assumptions. Results were interpreted for statistically and clinically significant differences. Results: Of 168 patients randomized 1 : 1, n = 143 baseline HRQoL scores (85%) were calculated. Of these, 75 (89%) were in the TIL-IMP group and 73 (87%) in the IPI group. TIL-IMP-treated patients reported higher global health status scores at week 24 compared with IPI-treated patients (78.2 versus 73.9; P &lt; 0.05) and higher emotional functioning (85.9 versus 77.9; P &lt; 0.05) scores. Patients treated with TIL-IMP had significantly lower fatigue (25.0 versus 32.4; P &lt; 0.05) and pain (13.7 versus 17.6; P &lt; 0.05) scores at week 24, but marginally higher nausea and vomiting (7.5 versus 5.2; P &lt; 0.05) symptom scores. EQ-5D scores were also higher in the TIL-IMP group (0.89 versus 0.83; P &lt; 0.05). These statistically significant differences were not considered clinically meaningful. The hypothesized higher impact of the more intensive TIL-IMP treatment compared with IPI was not observed, according to IES scores (11.8 versus 17.4; P &lt; 0.05 at 24 weeks). Sensitivity analyses showed similar results.Conclusions: Patients with metastatic melanoma treated with TIL-IMP experienced similar HRQoL compared with IPI monotherapy, with indications of better HRQoL outcomes over time. Ongoing follow-up is essential to assess longer-term HRQoL and its generalizability to a larger patient population to help guide personalized treatment decisions.</p

Discontinuation of anti-PD-1 antibody therapy in the absence of disease progression or treatment limiting toxicity : clinical outcomes in advanced melanoma

Background Programmed cell death protein 1 (PD-1) blocking monoclonal antibodies improve the overall survival of patients with advanced melanoma but the optimal duration of treatment has not been established. Patients and Methods This academic real-world cohort study investigated the outcome of 185 advanced melanoma patients who electively discontinued anti-PD-1 therapy with pembrolizumab (N=167) or nivolumab (N=18) in the absence of disease progression (PD) or treatment limiting toxicity (TLT) at 14 medical centres across Europe and Australia. Results Median time on treatment was 12months (range 0.7-43). The best objective tumour response at the time of treatment discontinuation was complete response (CR) in 117 (63%) patients, partial response (PR) in 44 (24%) patients and stable disease (SD) in 16 (9%) patients; 8 (4%) patients had no evaluable disease (NE). After a median follow-up of 18months (range 0.7-48) after treatment discontinuation, 78% of patients remained free of progression. Median time to progression was 12months (range 2-23). PD was less frequent in patients with CR (14%) compared with patients with PR (32%) and SD (50%). Six out of 19 (32%) patients who were retreated with an anti-PD-1 at the time of PD obtained a new antitumour response. Conclusions In this real-world cohort of advanced melanoma patients discontinuing anti-PD-1 therapy in the absence of TLT or PD, the duration of anti-PD-1 therapy was shorter when compared with clinical trials. In patients obtaining a CR, and being treated for >6months, the risk of relapse after treatment discontinuation was low. Patients achieving a PR or SD as best tumour response were at higher risk for progression after discontinuing therapy, and defining optimal treatment duration in such patients deserves further study. Retreatment with an anti-PD-1 at the time of progression may lead to renewed antitumour activity in some patients. Clinical trial registration NCT02673970 (https://clinicaltrials.gov/ct2/show/NCT02673970?cond=melanoma&cntry=BE&city=Jette&rank=3)Peer reviewe

DHPR activation underlies SR Ca2+ release induced by osmotic stress in isolated rat skeletal muscle fibers

Changes in skeletal muscle volume induce localized sarcoplasmic reticulum (SR) Ca2+ release (LCR) events, which are sustained for many minutes, suggesting a possible signaling role in plasticity or pathology. However, the mechanism by which cell volume influences SR Ca2+ release is uncertain. In the present study, rat flexor digitorum brevis fibers were superfused with isoosmotic Tyrode's solution before exposure to either hyperosmotic (404 mOsm) or hypoosmotic (254 mOsm) solutions, and the effects on cell volume, membrane potential (Em), and intracellular Ca2+ ([Ca2+]i) were determined. To allow comparison with previous studies, solutions were made hyperosmotic by the addition of sugars or divalent cations, or they were made hypoosmotic by reducing [NaCl]o. All hyperosmotic solutions induced a sustained decrease in cell volume, which was accompanied by membrane depolarization (by 14–18 mV; n = 40) and SR Ca2+ release. However, sugar solutions caused a global increase in [Ca2+]i, whereas solutions made hyperosmotic by the addition of divalent cations only induced LCR. Decreasing osmolarity induced an increase in cell volume and a negative shift in Em (by 15.04 ± 1.85 mV; n = 8), whereas [Ca2+]i was unaffected. However, on return to the isoosmotic solution, restoration of cell volume and Em was associated with LCR. Both global and localized SR Ca2+ release were abolished by the dihydropyridine receptor inhibitor nifedipine by sustained depolarization of the sarcolemmal or by the addition of the ryanodine receptor 1 inhibitor tetracaine. Inhibitors of the Na-K-2Cl (NKCC) cotransporter markedly inhibited the depolarization associated with hyperosmotic shrinkage and the associated SR Ca2+ release. These findings suggest (1) that the depolarization that accompanies a decrease in cell volume is the primary event leading to SR Ca2+ release, and (2) that volume-dependent regulation of the NKCC cotransporter contributes to the observed changes in Em. The differing effects of the osmotic agents can be explained by the screening of fixed charges by divalent ions

Age and gender differences in narcissism: A comprehensive study across eight measures and over 250,000 participants

Age and gender differences in narcissism have been studied often. However, considering the rich history of narcissism research accompanied by its diverging conceptualizations, little is known about age and gender differences across various narcissism measures. The present study investigated age and gender differences and their interactions across eight widely used narcissism instruments (i.e., Narcissistic Personality Inventory, Hypersensitive Narcissism Scale, Dirty Dozen, Psychological Entitlement Scale, Narcissistic Personality Disorder Symptoms from the Diagnostic and Statistical Manual of Mental Disorders, Version IV, Narcissistic Admiration and Rivalry Questionnaire-Short Form, Single-Item Narcissism Scale, and brief version of the Pathological Narcissism Inventory). The findings of Study 1 (N = 5,736) revealed heterogeneity in how strongly the measures are correlated. Some instruments loaded clearly on one of the three factors proposed by previous research (i.e., Neuroticism, Extraversion, Antagonism), while others cross-loaded across factors and in distinct ways. Cross-sectional analyses using each measure and meta-analytic results across all measures (Study 2) with a total sample of 270,029 participants suggest consistent linear age effects (random effects meta-analytic effect of r = -.104), with narcissism being highest in young adulthood. Consistent gender differences also emerged (random effects meta-analytic effect was -.079), such that men scored higher in narcissism than women. Quadratic age effects and Age × Gender effects were generally very small and inconsistent. We conclude that despite the various conceptualizations of narcissism, age and gender differences are generalizable across the eight measures used in the present study. However, their size varied based on the instrument used. We discuss the sources of this heterogeneity and the potential mechanisms for age and gender differences

A global experience‐sampling method study of well‐being during times of crisis: The CoCo project

We present a global experience-sampling method (ESM) study aimed at describing, predicting, and understanding individual differences in well-being during times of crisis such as the COVID-19 pandemic. This international ESM study is a collaborative effort of over 60 interdisciplinary researchers from around the world in the “Coping with Corona” (CoCo) project. The study comprises trait-, state-, and daily-level data of 7490 participants from over 20 countries (total ESM measurements = 207,263; total daily measurements = 73,295) collected between October 2021 and August 2022. We provide a brief overview of the theoretical background and aims of the study, present the applied methods (including a description of the study design, data collection procedures, data cleaning, and final sample), and discuss exemplary research questions to which these data can be applied. We end by inviting collaborations on the CoCo dataset