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SUMMARY The ambient infrasonic noise field is complex due to the interference of spatially distributed infrasound sources. Microbaroms are one of the most dominant omnipresent infrasonic sources within this wavefield. These microbaroms are generated by nonlinear ocean surface wave interactions, and have a characteristic and continuous signature within the infrasound spectrum. Under noisy conditions, microbaroms can mask infrasonic signals of interest, such as infrasound from volcanoes or explosions, which limits detection and identification of such sources. This study performs an infrasonic climatology for infrasound array I23FR, using five years of data between 2015–2020. The array is located on the Kerguelen Islands, within the Southern Ocean, and is part of the International Monitoring System for the verification of the Comprehensive Nuclear-Test-Ban Treaty. The climatology analysis addresses the expected ambient noise levels, propagation paths and potential sources within the vicinity of an infrasound sensor. Time- and frequency-domain beamforming methods have been applied to analyse the infrasonic wavefield from the I23FR observations. A recently introduced method is applied to compute so-called soundscapes, to be compared with beamform results. Although the comparison indicates a disagreement in amplitude, there is a good agreement in directionality and frequency between both.

Contains fulltext : 247514.pdf (Publisher’s version ) (Closed access) Motivations shape our behaviour: the promise of reward invigorates, while in the face of punishment, we hold back. Abnormalities of motivational processing are implicated in clinical disorders characterised by excessive habits and loss of top-down control, notably substance and behavioural addictions. Striatal and frontal dopamine have been hypothesised to play complementary roles in the respective generation and control of these motivational biases. However, while dopaminergic interventions have indeed been found to modulate motivational biases, these previous pharmacological studies used regionally non-selective pharmacological agents. Here, we tested the hypothesis that frontal dopamine controls the balance between Pavlovian, bias-driven automated responding and instrumentally learned action values. Specifically, we examined whether selective enhancement of cortical dopamine either (i) enables adaptive suppression of Pavlovian control when biases are maladaptive; or (ii) non-specifically modulates the degree of bias-driven automated responding. Healthy individuals (n = 35) received the catechol-o-methyltransferase (COMT) inhibitor tolcapone in a randomised, double-blind, placebo-controlled cross-over design, and completed a motivational Go NoGo task known to elicit motivational biases. In support of hypothesis (ii), tolcapone globally decreased motivational bias. Specifically, tolcapone improved performance on trials where the bias was unhelpful, but impaired performance in bias-congruent conditions. These results indicate a non-selective role for cortical dopamine in the regulation of motivational processes underpinning top-down control over automated behaviour. The findings have direct relevance to understanding neurobiological mechanisms underpinning addiction and obsessive-compulsive disorders, as well as highlighting a potential trans-diagnostic novel mechanism to address such symptoms. 10 p.

Purpose: PCR-based detection of minimal residual disease (MRD) in neuroblastoma (NB) is presently based on NB-specific transcripts. However, the expression of these targets varies between patients and upon treatment, and only PHOX2B is truly specific. RASSF1a is methylated (RASSF1aM) in NB, and we investigated whether it can serve as a specific and stable DNA MRD marker.Patients and Methods: The RASSF1aM-specific quantitative real-time PCR was tested on control bone marrow (BM; n = 50), on 71 NB tumors, and on 159 clinical BM samples at diagnosis and at follow-up of 77 patients. Results were compared with a panel of RNA markers and correlated with prognosis.Results: RASSF1aM was present in all stage 4 and 4s tumors (n = 50) and in 86% stages 1 to 3 tumors (n = 21). The level of methylation in stage 4 NB was correlated with overall survival (P = 0.02). RASSF1aM–PCR was highly specific (only 1 amplification in 50 control samples tested in triplicate) and had a similar sensitivity as the RNA-based PCRs, as shown on clinical samples. Moreover, RASSF1aM enabled accurate quantification without need for the original tumor.Conclusions: RASSF1aM is a novel, highly specific DNA marker for MRD detection in NB, equal to PHOX2B in specificity and sensitivity, and better suitable for MRD quantification. We propose to include RASSF1aM in further prospective MRD studies in NB alongside RNA MRD markers. In addition, this assay might also be applicable for detection of circulating tumor cells in patients with other cancers withRASSF1aM such as breast or lung cancer. Clin Cancer Res; 18(3); 808–14. ©2011 AACR.

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The molecular mechanisms contributing to immune suppression in ovarian cancer are not well understood, hampering the successful application of immunotherapy. Amino acid-metabolizing enzymes are known to contribute to the immune-hostile environment of various tumors through depletion of amino acids and production of immunosuppressive metabolites. We aimed to collectively evaluate the activity of these enzymes in high-grade serous ovarian cancer patients by performing targeted metabolomics on plasma and ascites samples. Whereas no indication was found for enhanced l-arginine or l-glutamine metabolism by immunosuppressive enzymes in ovarian cancer patients, metabolism of l-tryptophan by indoleamine 2,3-dioxygenase 1 (IDO1) was significantly elevated compared to healthy controls. Moreover, high levels of l-phenylalanine- and l-tyrosine-derived metabolites associated with interleukin 4 induced 1 (IL4I1) activity were found in ovarian cancer ascites samples. While l-tryptophan is a major substrate of both IDO1 and IL4I1, only its enhanced conversion into l-kynurenine by IDO1 could be detected, despite the observed activity of IL4I1 on its other substrates. In ascites of ovarian cancer patients, metabolite levels were higher compared to those in plasma, demonstrating the value of utilizing this fluid for biomarker identification. Finally, elevated metabolism of l-phenylalanine and l-tyrosine by IL4I1 correlated with disease stage, pointing towards a potential role for IL4I1 in ovarian cancer progression.

Background Mobile health apps are promising tools to help patients with type 2 diabetes mellitus (T2DM) improve their health status and thereby achieve diabetes control and self-management. Although there is a wide array of mobile health apps for T2DM available at present, apps are not yet integrated into routine diabetes care. Acceptability and acceptance among patients with T2DM is a major challenge and prerequisite for the successful implementation of apps in diabetes care. Objective This study provides an in-depth understanding of the perceptions of patients with T2DM before use (acceptability) and after use (acceptance) regarding 4 different mobile health apps for diabetes control and self-management. Methods A descriptive qualitative research design was used in this study. Participants could choose 1 of the 4 selected apps for diabetes control and self-management (ie, Clear.bio in combination with FreeStyle Libre, mySugr, MiGuide, and Selfcare). The selection was based on a systematic analysis of the criteria for (functional) requirements regarding monitoring, data collection, provision of information, coaching, privacy, and security. To explore acceptability, 25 semistructured in-depth interviews were conducted with patients with T2DM before use. This was followed by 4 focus groups to discuss the acceptance after use. The study had a citizen science approach, that is, patients with T2DM collaborated with researchers as coresearchers. All coresearchers actively participated in the preparation of the study, data collection, and data analysis. Data were collected between April and September 2021. Thematic analysis was conducted using a deductive approach using AtlasTi9. Results In total, 25 coresearchers with T2DM participated in this study. Of them, 12 coresearchers tested Clear, 5 MiGuide, 4 mySugr, and 4 Selfcare. All coresearchers participated in semistructured interviews, and 18 of them attended focus groups. Personal health was the main driver of app use. Most coresearchers were convinced that a healthy lifestyle would improve blood glucose levels. Although most coresearchers did not expect that they need to put much effort into using the apps, the additional effort to familiarize themselves with the app use was experienced as quite high. None of the coresearchers had a health care professional who provided suggestions on using the apps. Reimbursement from insurance companies and the acceptance of apps for diabetes control and self-management by the health care system were mentioned as important facilitating conditions. Conclusions The research showed that mobile health apps provide support for diabetes control and self-management in patients with T2DM. Integrating app use in care as usual and guidelines for health care professionals are recommended. Future research is needed on how to increase the implementation of mobile health apps in current care pathways. In addition, health care professionals need to improve their digital skills, and lifelong learning is recommended.

IntroductionPositive social comparative feedback indicates to the learner that they are performing better than others. While this type feedback supports motor skill learning in some tasks, the effect of social comparative feedback on implicit motor sequence learning remains unknown. The aim of this study was to determine the effect of positive social comparative feedback on the learning of and expectancies for a motor sequence task.MethodsForty-eight individuals practiced a joystick-based sequence task and were divided into three feedback groups: CONTROL (no performance feedback), RT ONLY (response time only feedback), and RT+POS (response time plus positive social comparison). Participants attended sessions on two consecutive days: Day 1 for repetitive motor practice/skill acquisition and Day 2 for retention testing. Performance related expectancies, like perceived competence, were measured before and after motor practice on Day 1 and at retention on Day 2.ResultsWhile all groups improved with practice, the CONTROL group showed better overall performance/learning (faster response times) compared with the RT ONLY group. Despite similar response times, the RT+POS showed higher peak velocities than the RT ONLY group. Overall, the RT+POS and CONTROL demonstrated increases in perceived competence while the RT ONLY group did not.DiscussionThe results of this study suggest that feedback content is an important consideration during motor practice sessions since feedback without context (RT ONLY) may be detrimental to motor sequence learning. The results also suggest that, if providing performance related feedback during practice of a skill that relies on implicit sequence learning processes, comparative context may be necessary for enhancing expectancies and supporting.

High demands on forest for carbon storage and provision of timber and biofuel require precise and reliable estimates of the biomass, carbon and nutrient stocks in different tree compartments. Whether the fraction of biomass distributed in aboveground tree compartments and the carbon and nutrient concentrations varies systematically across trees in different canopy positions remains unclear despite its importance for understanding forest ecology. Here, we compared the distribution of biomass, carbon and nutrients from underlying carbon and nutrient concentrations between different aboveground tree compartments for 15 mature trees of European beech (Fagus sylvatica), Douglas fir (Pseudotsuga menziesii) and Scots pine (Pinus sylvestris) with dominant, intermediate and suppressed canopy position. We show that carbon concentrations were relatively constant across tree compartments while nutrient concentrations increased from stem, bark, branches towards needles. Canopy position had only minor effects on carbon and nutrient concentrations and on the distribution of biomass, carbon and nutrients between aboveground tree components. Nutrient concentrations and stochiometric results confirm that the forests were affected by high N deposition and low availability of P and base cations. Our results imply that predictions from allometric scaling theory better apply to aboveground tree components than from functional equilibrium theory. Models aiming for estimating tree and forest biomass and carbon and nutrient stocks can apply equal biomass, carbon and nutrient stocks for trees independent of canopy position as a valid assumption but testing this assumption for a broader range of species and site conditions remains recommended.

The ability to generalize previously learned information to novel situations is key for adaptive behavior. Here, we investigated the neural mechanisms underlying the ability to infer novel compositional word meanings using a novel behavioral paradigm. Participants were trained on compositional word meaning from an artificial language comprising extant stems (“good”) and novel affixes (“kla”). The meaning of the compositional words depended on the position of the novel affix (“goodkla = bad”, “klahorse = pony”). We then asked them to infer the meaning of novel compositional words (“whitekla =?”, “klacat =?”) which were either congruent or incongruent with the rule (“klawhite” is incongruent because a small version of “white” does not exist). During fMRI, participants performed a semantic priming task in which the novel words served as congruent or incongruent primes (“whitekla”) and their synonyms (“black”) served as targets. Our results show that people are able to generate novel compositional meanings on the fly, successfully inferring meanings of congruent versus incongruent words. Repetition suppression effects at target were greater when primed with congruent than incongruent words in the left inferior frontal gyrus, suggesting the novel meanings to be derived at this linguistic “building” hub. Analysis of congruent versus incongruent prime-related activity revealed a broad frontal-parietal network, including hippocampus, the brain area commonly associated with the generalization process of structural relationships. We argue that generative compositionality in language recruits a domain-general network shared with action planning, compositional vision and constructive relational memory, while the newly inferred meanings are represented in more language-specific regions.

Background Coronavirus disease 2019 (COVID-19) has been especially dangerous for elderly people. To reduce the risk of transmission from healthcare workers to elderly people, it is of utmost importance to detect possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive healthcare workers as early as possible. We aimed to determine whether the Abbott Panbio™ COVID-19 antigen detection rapid diagnostic test (Ag-RDT) could be used as an alternative to reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The second aim was to compare the cycle threshold (Ct) in RT-qPCR with the results of the Ag-RDT. Methods A prospective diagnostic evaluation of the Abbott Panbio™ COVID-19 Ag-RDT among healthcare workers across three elderly care facilities as well as home-based elderly care workers who met clinical criteria for COVID-19 during the second wave of the COVID-19 pandemic. Per healthcare worker, the first nasopharyngeal swab was obtained to perform the Ag-RDT and the second swab for RT-qPCR. A Ct-value of < 40 was interpreted as positive, ≥ 40 as negative. Results A total of 683 healthcare workers with COVID-19 symptoms were sampled for detection of SARS-CoV-2 by both Ag-RDT and RT-qPCR. Sixty-three healthcare workers (9.2%) tested positive for SARS-CoV-2 by RT-qPCR. The overall sensitivity of Ag-RDT was 81.0% sensitivity (95%CI: 69.6–88.8%) and 100% specificity (95%CI: 99.4–100%). Using a cut-off Ct-value of 32, the sensitivity increased to 92.7% (95% CI: 82.7–97.1%). Negative Ag-RDT results were moderately associated with higher Ct-values (r = 0.62) compared to positive Ag-RDT results. Conclusion The Panbio™ COVID-19 Ag-RDT can be used to quickly detect positive SARS-CoV-2 healthcare workers. Negative Ag-RDT should be confirmed by RT-qPCR. In case of severe understaffing and with careful consideration, fully vaccinated healthcare workers with Ag-RDT negative results could work with a mask pending PCR results.

Contains fulltext : 290609.pdf (Publisher’s version ) (Open Access) Genome sequencing (GS) can identify novel diagnoses for patients who remain undiagnosed after routine diagnostic procedures. We tested whether GS is a better first-tier genetic diagnostic test than current standard of care (SOC) by assessing the technical and clinical validity of GS for patients with neurodevelopmental disorders (NDD). We performed both GS and exome sequencing in 150 consecutive NDD patient-parent trios. The primary outcome was diagnostic yield, calculated from disease-causing variants affecting exonic sequence of known NDD genes. GS (30%, n = 45) and SOC (28.7%, n = 43) had similar diagnostic yield. All 43 conclusive diagnoses obtained with SOC testing were also identified by GS. SOC, however, required integration of multiple test results to obtain these diagnoses. GS yielded two more conclusive diagnoses, and four more possible diagnoses than ES-based SOC (35 vs. 31). Interestingly, these six variants detected only by GS were copy number variants (CNVs). Our data demonstrate the technical and clinical validity of GS to serve as routine first-tier genetic test for patients with NDD. Although the additional diagnostic yield from GS is limited, GS comprehensively identified all variants in a single experiment, suggesting that GS constitutes a more efficient genetic diagnostic workflow. 01 januari 2023

The sustainability of tree harvest is questioned since harvest results in increased nutrient losses which may reduce nutrient stocks in forest soils, particularly in forests on acidified and poor soils with low base saturation. We used a new forest experiment to quantify nutrient stocks and nutrient uptake rates in mature forest stands, and to assess the forest nutrient balance in relation to different forest management scenarios: clearcutting, shelterwood and thinning; and whole-tree harvest (WTH), stem-only harvest (SOH) and wood only harvest (WOH, with on-site bark stripping). Forests were dominated by trees of Fagus sylvatica, Pseudotsuga Menziesii or Pinus sylvestris, all situated on poor, acidified soils. We measured forest biomass and nutrient stocks based on destructive sampling of fifteen mature trees per species and by using new, calibrated allometric relationships. Aboveground stocks of N, P, S, K, Ca, Mg, Mn, Cu, Fe and Zn were calculated for foliage, branches, stem bark and stem wood. Annual forest growth and nutrient uptake were determined using tree ring measures and allometric relationships. Organic layer nutrient stocks and available nutrients in the mineral soil were determined following intensive soil sampling. Stands of beech, Douglas fir and Scots pine differed in aboveground biomass and nutrient stocks, with highest biomass stocks in Douglas fir. However, beech stands had the highest aboveground nutrient stocks, nutrient uptake rates and nutrient losses following harvest, followed by Scots pine. Organic layer nutrient stocks generally exceeded aboveground nutrient stocks, except for the base cations and Mn. Compared to SOH, WTH increased nutrient export between 66% (Douglas fir) up to 100% (Scots pine), while WOH decreased the nutrient export between 23% (beech) up to 41% (Douglas fir). High aboveground base cation and Mn stocks indicate potential long-term threats to forest nutrition if trees are harvested. However, in Douglas fir stands, nutrient losses through SOH may fully recover when using rotation periods of 80 years. Contrary, negative Ca balances are predicted when applying SOH in beech and Scots pine, since Ca stocks are potentially depleted within 2 final fellings. WTH poses, regardless of the species, potential threats for sustainable biomass harvest as nutrients cannot be recovered using common rotation periods. WOH conserves nutrients within the forest posing opportunities for sustainable biomass harvest. For similar temperate forest on acidified, sandy soils, we therefore recommend to limit tree harvest depending on the tree species, and to avoid WTH and consider WOH to better conserve critical nutrients required for long-term forest recovery.

The study of market power has gained a lot of attention by scholars and policy-makers since De Loecker and Eeckhout (Global market power. Working paper 24768, National Bureau of Economic Research, 2018). In their work, they show the temporal evolution of market power worldwide using detailed data from the financial statements of thousands of firms. In this paper, we propose an alternative way of estimating market power using sectoral-based data. By utilizing the aggregates observable in a series of input–output tables and by applying an estimation procedure based on entropy; indicators of market power can be derived without requiring the use of micro-data. We document a heterogeneous evolution of market power across 28 European countries and 14 manufacturing sectors between 2000 and 2014. Market power is found to be rising for several central- and East-European countries, while decreasing in multiple South- and West-European nations. Globalisation and value chain positioning are both seen to have a significantly decreasing impact on markups.

Prospective outcomes bias behavior in a “Pavlovian” manner: Reward prospect invigorates action, while punishment prospect suppresses it. Theories have posited Pavlovian biases as global action “priors” in unfamiliar or uncontrollable environments. However, this account fails to explain the strength of these biases—causing frequent action slips—even in well-known environments. We propose that Pavlovian control is additionally useful if flexibly recruited by instrumental control. Specifically, instrumental action plans might shape selective attention to reward/ punishment information and thus the input to Pavlovian control. In two eye-tracking samples (N = 35/ 64), we observed that Go/ NoGo action plans influenced when and for how long participants attended to reward/ punishment information, which in turn biased their responses in a Pavlovian manner. Participants with stronger attentional effects showed higher performance. Thus, humans appear to align Pavlovian control with their instrumental action plans, extending its role beyond action defaults to a powerful tool ensuring robust action execution.