Deep learning models for automatic tumor segmentation and total tumor volume assessment in patients with colorectal liver metastases.

BACKGROUND: We developed models for tumor segmentation to automate the assessment of total tumor volume (TTV) in patients with colorectal liver metastases (CRLM). METHODS: In this prospective cohort study, pre- and post-systemic treatment computed tomography (CT) scans of 259 patients with initially unresectable CRLM of the CAIRO5 trial (NCT02162563) were included. In total, 595 CT scans comprising 8,959 CRLM were divided into training (73%), validation (6.5%), and test sets (21%). Deep learning models were trained with ground truth segmentations of the liver and CRLM. TTV was calculated based on the CRLM segmentations. An external validation cohort was included, comprising 72 preoperative CT scans of patients with 112 resectable CRLM. Image segmentation evaluation metrics and intraclass correlation coefficient (ICC) were calculated. RESULTS: In the test set (122 CT scans), the autosegmentation models showed a global Dice similarity coefficient (DSC) of 0.96 (liver) and 0.86 (CRLM). The corresponding median per-case DSC was 0.96 (interquartile range [IQR] 0.95-0.96) and 0.80 (IQR 0.67-0.87). For tumor segmentation, the intersection-over-union, precision, and recall were 0.75, 0.89, and 0.84, respectively. An excellent agreement was observed between the reference and automatically computed TTV for the test set (ICC 0.98) and external validation cohort (ICC 0.98). In the external validation, the global DSC was 0.82 and the median per-case DSC was 0.60 (IQR 0.29-0.76) for tumor segmentation. CONCLUSIONS: Deep learning autosegmentation models were able to segment the liver and CRLM automatically and accurately in patients with initially unresectable CRLM, enabling automatic TTV assessment in such patients. RELEVANCE STATEMENT: Automatic segmentation enables the assessment of total tumor volume in patients with colorectal liver metastases, with a high potential of decreasing radiologist's workload and increasing accuracy and consistency. KEY POINTS: • Tumor response evaluation is time-consuming, manually performed, and ignores total tumor volume. • Automatic models can accurately segment tumors in patients with colorectal liver metastases. • Total tumor volume can be accurately calculated based on automatic segmentations.

Knowledge of collision modulates defensive multisensory responses to looming insects in arachnophobes.

We investigated the role of contextual knowledge in defensive responses to visual stimuli (spiders and butterflies) looming toward the hand. Human participants responded to tactile stimuli delivered to the same hand at 6 possible locations during an insect's approach. Tactile reaction times were faster when looming stimuli were closer to the hand, especially for spiders, and faster when insects loomed on a collision path than on a near-miss path. This latter finding suggests that human reactions to looming stimuli are not merely automatic reflexes but that contextual knowledge about the trajectory of looming objects is included in predicting their impact. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The role of coupled DNRA-Anammox during nitrate removal in a highly saline lake.

Nitrate (NO3-) removal from aquatic ecosystems involves several microbially mediated processes, including denitrification, dissimilatory nitrate reduction to ammonium (DNRA), and anaerobic ammonium oxidation (anammox), controlled by slight changes in environmental gradients. In addition, some of these processes (i.e. denitrification) may involve the production of undesirable compounds such as nitrous oxide (N2O), an important greenhouse gas. Saline lakes are prone to the accumulation of anthropogenic contaminants, making them highly vulnerable environments to NO3- pollution. The aim of this paper was to investigate the effect of light and oxygen on the different NO3- removal pathways under highly saline conditions. For this purpose, mesocosm experiments were performed using lacustrine, undisturbed, organic-rich sediments from the Pétrola Lake (Spain), a highly saline waterbody subject to anthropogenic NO3- pollution. The revised 15N-isotope pairing technique (15N-IPT) was used to determine NO3- sink processes. Our results demonstrate for the first time the coexistence of denitrification, DNRA, and anammox processes in a highly saline lake, and how their contribution was determined by environmental conditions (oxygen and light). DNRA, and especially denitrification to N2O, were the dominant nitrogen (N) removal pathways when oxygen and/or light were present (up to 82%). In contrast, anoxia and darkness promoted NO3- reduction by DNRA (52%), combined with N loss by anammox (28%). Our results highlight the role of coupled DNRA-anammox, which has not yet been investigated in lacustrine sediments. We conclude that anoxia and darkness favored DNRA and anammox processes over denitrification and therefore to restrict N2O emissions to the atmosphere.

KRAS A146 Mutations Are Associated With Distinct Clinical Behavior in Patients With Colorectal Liver Metastases.

Somatic KRAS mutations occur in approximately half of the patients with metastatic colorectal cancer (mCRC). Biologic tumor characteristics differ on the basis of the KRAS mutation variant. KRAS mutations are known to influence patient prognosis and are used as predictive biomarker for treatment decisions. This study examined clinical features of patients with mCRC with a somatic mutation in KRAS G12, G13, Q61, K117, or A146. METHODS: A total of 419 patients with colorectal cancer with initially unresectable liver-limited metastases, who participated in a multicenter prospective trial, were evaluated for tumor tissue KRAS mutation status. For the subgroup of patients who carried a KRAS mutation and were treated with bevacizumab and doublet or triplet chemotherapy (N = 156), pretreatment circulating tumor DNA levels were analyzed, and total tumor volume (TTV) was quantified on the pretreatment computed tomography images. RESULTS: Most patients carried a KRAS G12 mutation (N = 112), followed by mutations in G13 (N = 15), A146 (N = 12), Q61 (N = 9), and K117 (N = 5). High plasma circulating tumor DNA levels were observed for patients carrying a KRAS A146 mutation versus those with a KRAS G12 mutation, with median mutant allele frequencies of 48% versus 19%, respectively. Radiologic TTV revealed this difference to be associated with a higher tumor load in patients harboring a KRAS A146 mutation (median TTV 672 cm3 [A146] v 74 cm3 [G12], P = .036). Moreover, KRAS A146 mutation carriers showed inferior overall survival compared with patients with mutations in KRAS G12 (median 10.7 v 26.4 months; hazard ratio = 2.5; P = .003). CONCLUSION: Patients with mCRC with a KRAS A146 mutation represent a distinct molecular subgroup of patients with higher tumor burden and worse clinical outcomes, who might benefit from more intensive treatments. These results highlight the importance of testing colorectal cancer for all KRAS mutations in routine clinical care.

Thermal Ablation versus Stereotactic Ablative Body Radiotherapy to Treat Unresectable Colorectal Liver Metastases: A Comparative Analysis from the Prospective Amsterdam CORE Registry.

Thermal ablation and stereotactic ablative radiotherapy (SABR) are techniques to eradicate colorectal liver metastases (CRLM). This study compares the safety, efficacy and long-term oncological outcomes of these treatment methods. All prospectively registered patients (AmCORE registry) treated with thermal ablation or SABR alone for unresectable CRLM between 2007 and 2020 were analyzed using multivariate Cox-proportional hazard regression. In total 199 patients were included for analysis: 144 (400 CRLM) thermal ablation; 55 (69 CRLM) SABR. SABR patients were characterized by older age (p = 0.006), extrahepatic disease at diagnosis (p = 0.004) and larger tumors (p < 0.001). Thermal ablation patients were more likely to have synchronous disease, higher clinical risk scores (p = 0.030) and higher numbers of CRLMs treated (p < 0.001). Mortality was zero and morbidity low in both groups: no serious adverse events were recorded following SABR (n = 0/55) and nine (n = 9/144 [6.3%]; all CTCAE grade 3) after thermal ablation. SABR was associated with an inferior overall survival (OS) (median OS 53.0 months vs. 27.4 months; HR = 1.29, 95% CI 1.12-1.49; p = 0.003), local tumor progression-free survival (LTPFS) per-tumor (HR = 1.24, 95% CI 1.01-1.52; p = 0.044) and local control per-patient (HR = 1.57, 95% CI 1.20-2.04; p = 0.001) and per-tumor (HR = 1.89, 95% CI 1.44-2.49; p < 0.001). In this study thermal ablation was superior to SABR with regard to OS, LTPFS and local control, albeit at the cost of a limited risk of serious adverse events. Further studies are required to assess whether the worse outcomes following SABR were the effect of true differences in ablative treatment or a result of residual confounding.

Survival Benefit of Repeat Local Treatment in Patients Suffering From Early Recurrence of Colorectal Cancer Liver Metastases.

BACKGROUND: A uniform treatment strategy for patients suffering from early recurrence after local treatment of CRLM is currently lacking. The aim of this observational cohort study was to assess the potential survival benefit of repeat local treatment compared to systemic therapy in patients suffering from early recurrence of CRLM. PATIENTS AND METHODS: Patients who developed recurrent CRLM within 12 months after initial local treatment with curative intent were retrospectively identified in Amsterdam University Medical Centers between 2009-2019. Differences in overall and progression-free survival among treatment strategies were assessed using multivariable Cox regression analyses. RESULTS: A total of 135 patients were included. Median overall survival of 41 months [range 4-135] was observed in patients who received repeat local treatment, consisting of upfront or repeat local treatment after neoadjuvant systemic therapy, compared to 24 months [range 1-55] in patients subjected to systemic therapy alone (adjusted HR = 0.42 [95%-CI: 0.25-0.72]; P = .002). Prolonged progression-free survival was observed after neoadjuvant systemic therapy followed by repeat local treatment, as compared to upfront repeat local treatment in patients with recurrent CRLM within 4 months following initial local treatment of CRLM (adjusted HR = 0.36 [95%-CI: 0.15-0.86]; P = .021). CONCLUSION: Patients with early recurrence of CRLM should be considered for repeat local treatment strategies. A multimodality approach, consisting of neoadjuvant systemic therapy followed by repeat local treatment, appeared favorable in patients with recurrence within 4 months following initial local treatment of CRLM.

The Redundant Signals Effect and the Full Body Illusion: not Multisensory, but Unisensory Tactile Stimuli Are Affected by the Illusion.

During a full body illusion (FBI), participants experience a change in self-location towards a body that they see in front of them from a third-person perspective and experience touch to originate from this body. Multisensory integration is thought to underlie this illusion. In the present study we tested the redundant signals effect (RSE) as a new objective measure of the illusion that was designed to directly tap into the multisensory integration underlying the illusion. The illusion was induced by an experimenter who stroked and tapped the participant's shoulder and underarm, while participants perceived the touch on the virtual body in front of them via a head-mounted display. Participants performed a speeded detection task, responding to visual stimuli on the virtual body, to tactile stimuli on the real body and to combined (multisensory) visual and tactile stimuli. Analysis of the RSE with a race model inequality test indicated that multisensory integration took place in both the synchronous and the asynchronous condition. This surprising finding suggests that simultaneous bodily stimuli from different (visual and tactile) modalities will be transiently integrated into a multisensory representation even when no illusion is induced. Furthermore, this finding suggests that the RSE is not a suitable objective measure of body illusions. Interestingly however, responses to the unisensory tactile stimuli in the speeded detection task were found to be slower and had a larger variance in the asynchronous condition than in the synchronous condition. The implications of this finding for the literature on body representations are discussed.

The Prognostic Value of Total Tumor Volume Response Compared With RECIST1.1 in Patients With Initially Unresectable Colorectal Liver Metastases Undergoing Systemic Treatment.

Objectives: Compare total tumor volume (TTV) response after systemic treatment to Response Evaluation Criteria in Solid Tumors (RECIST1.1) and assess the prognostic value of TTV change and RECIST1.1 for recurrence-free survival (RFS) in patients with colorectal liver-only metastases (CRLM). Background: RECIST1.1 provides unidimensional criteria to evaluate tumor response to systemic therapy. Those criteria are accepted worldwide but are limited by interobserver variability and ignore potentially valuable information about TTV. Methods: Patients with initially unresectable CRLM receiving systemic treatment from the randomized, controlled CAIRO5 trial (NCT02162563) were included. TTV response was assessed using software specifically developed together with SAS analytics. Baseline and follow-up computed tomography (CT) scans were used to calculate RECIST1.1 and TTV response to systemic therapy. Different thresholds (10%, 20%, 40%) were used to define response of TTV as no standard currently exists. RFS was assessed in a subgroup of patients with secondarily resectable CRLM after induction treatment. Results: A total of 420 CT scans comprising 7820 CRLM in 210 patients were evaluated. In 30% to 50% (depending on chosen TTV threshold) of patients, discordance was observed between RECIST1.1 and TTV change. A TTV decrease of >40% was observed in 47 (22%) patients who had stable disease according to RECIST1.1. In 118 patients with secondarily resectable CRLM, RFS was shorter for patients with less than 10% TTV decrease compared with patients with more than 10% TTV decrease (P = 0.015), while RECIST1.1 was not prognostic (P = 0.821). Conclusions: TTV response assessment shows prognostic potential in the evaluation of systemic therapy response in patients with CRLM.

Availability of synchronous information in an additional sensory modality does not enhance the full body illusion.

The Full body illusion (FBI) is an illusion in which participants experience a change in self-location to a body that is perceived from a third-person perspective. The FBI is usually induced through experimenter generated stroking but can also be induced through self-generated stroking. In four experiments (three preregistered) we compared a self-generated stroking induction condition to a self-generated movement condition, where the only difference between conditions was the presence or absence of touch. We investigated whether the illusion reflects an all-or-nothing phenomenon or whether the illusion is influenced by the availability of synchronous information in an additional sensory modality. As a prerequisite, we investigated whether the FBI can also be induced using just self-generated movement in the absence of synchronous touch. Illusion strength was measured through illusion statements. Participants reported an equally strong illusion for both induction methods in Experiments 1, 2 and 3. In the third experiment, we additionally measured the time of illusion onset. Like the illusion strength measures, the illusion onset times did not differ between the two induction methods. In the fourth experiment participants only completed the self-generated movement condition. Again, they reported the FBI, demonstrating that the findings of Experiments 1, 2 and 3 were not dependent on the presence of a condition that used synchronous touch. Together, these findings confirm the hypothesis that the FBI is an all-or-nothing phenomenon and that adding additional multisensory synchronicity does not help to enhance the strength, onset time or onset probability of the illusion.

Advanced analytics and artificial intelligence in gastrointestinal cancer: a systematic review of radiomics predicting response to treatment.

PURPOSE: Advanced medical image analytics is increasingly used to predict clinical outcome in patients diagnosed with gastrointestinal tumors. This review provides an overview on the value of radiomics in predicting response to treatment in patients with gastrointestinal tumors. METHODS: A systematic review was conducted, according to PRISMA guidelines. The protocol was prospectively registered (PROSPERO: CRD42019128408). PubMed, Embase, and Cochrane databases were searched. Original studies reporting on the value of radiomics in predicting response to treatment in patients with a gastrointestinal tumor were included. A narrative synthesis of results was conducted. Results were stratified by tumor type. Quality assessment of included studies was performed, according to the radiomics quality score. RESULTS: The comprehensive literature search identified 1360 unique studies, of which 60 articles were included for analysis. In 37 studies, radiomics models and individual radiomic features showed good predictive performance for response to treatment (area under the curve or accuracy > 0.75). Various strategies to construct predictive models were used. Internal validation of predictive models was often performed, while the majority of studies lacked external validation. None of the studies reported predictive models implemented in clinical practice. CONCLUSION: Radiomics is increasingly used to predict response to treatment in patients suffering from gastrointestinal cancer. This review demonstrates its great potential to help predict response to treatment and improve patient selection and early adjustment of treatment strategy in a non-invasive manner.

Event-related brain potentials reflect predictive coding of anticipated economic change.

Research has demonstrated the importance of economic forecasts for financial decisions at the aggregate economic level. However, little is known about the psychological and neurophysiological mechanisms that economic forecasts activate at the level of individual decision-making. In the present study, we used event-related brain potentials (ERPs) to test the hypothesis that economic forecasts influence individuals' internal model of the economy and their subsequent decision behavior. Using a simple economic decision-making game, the Balloon Analogue of Risk Task (BART) and predictive messages about possible economic changes in the game before each block, we test the idea that brain potentials time-locked to decision outcomes can vary as a function of exposure to economic forecasts. Behavioural results indicate that economic forecasts influenced the amount of risk that participants were willing to take. Analyses of brain potentials indicated parametric increases of the N1, P2, P3a, and P3b amplitudes as a function of the level of risk in subsequent inflation steps in the BART. Mismatches between economic forecasts and decision outcomes in the BART (i.e., reward prediction errors) were reflected in the amplitude of the P2, P3a, and P3b, suggesting increased attentional processing of unexpected outcomes. These electrophysiological results corroborate the idea that economic messages may indeed influence people's beliefs about the economy and bias their subsequent financial decision-making. Our findings present a first important step in the development of a low-level neurophysiological model that may help to explain the self-fulfilling prophecy effect of economic news in the larger economy.

Effects of environmental tobacco smoke exposure on brain functioning in never-smoking adolescents.

INTRODUCTION: Brain functioning, as indexed by event-related potentials (ERPs) representing smoking cue reactivity, inhibitory control, and reward processing, has been found to be compromised in smokers. However, whether environmental tobacco smoke (ETS) exposure in never smokers results in similar brain changes is unknown. This question is particularly relevant during adolescence, given ongoing brain maturation and a high risk of smoking initiation. The present study tested the associations between ETS exposure and ERPs reflecting cue reactivity (P3, LPP), inhibitory control (N2, P3), and reward processing (anticipation P3 (P3), feedback-related negativity (FRN)) among never-smoking adolescents. METHODS: Eighty-four never-smoking adolescents (nonexposed = 32, exposed = 52) performed a smoking cue reactivity, a Go/NoGo, and a monetary incentive delay (MID) task while ERPs were measured. RESULTS: Exposed and nonexposed groups did not differ in ERPs reflecting smoking cue reactivity, inhibitory control, and reward processing. A negative correlation between ETS exposure and the anticipatory P3 suggests reduced anticipatory reward sensitivity for nondrug rewards with increased levels of ETS exposure. However, since this effect was not consistent across analyses, no strong conclusions can be formulated. In the current study, few participants reported high levels of ETS exposure; therefore, further study is necessary. CONCLUSIONS: Nevertheless, from this study, it can be concluded that low-to-moderate exposure to ETS during adolescence does not result in functional brain changes related to smoking cue reactivity, inhibitory control, and reward processing.

Testing the Effectiveness of a Disclosure in Activating Children's Advertising Literacy in the Context of Embedded Advertising in Vlogs.

Watching vlogs of social media influencers has become a favorite pastime for children and adolescents. For advertisers, vlogs are an excellent way to reach young viewers. As such, vlogs have become a powerful marketing tool. However, for children and adolescents it is often unclear whether a vlog contains advertising, which raises questions regarding the fairness and transparency of this type of advertising. If children do not recognize the commercial intent of in-vlog advertising, then they are unlikely to activate their advertising literacy, which may serve as a critical coping mechanism. The aim of this study was to investigate if a sponsorship disclosure stimulates children and adolescents' (7-16 years old) to activate their advertising literacy when exposed to embedded advertising in vlogs and, subsequently, if advertising literacy activation is related to children's brand attitude. Furthermore, we investigated whether the relation between exposure to a sponsorship disclosure and advertising literacy activation was moderated by children's dispositional advertising literacy and their age. An innovative aspect of the current study is that advertising literacy activation was measured in two ways: with a self-reported questionnaire and via an indirect measurement task (Advertising Literacy Activation Task). The results showed that the children who were exposed to a sponsorship disclosure did not activate their advertising literacy to a higher extent than the children who were not exposed to such a disclosure. This might be because of the high prominence of the brand in the vlog; thus children may not have needed the disclosure to realize that the vlog was sponsored and accordingly activate their advertising literacy. The results also showed that stronger attitudinal advertising literacy activation led to a more negative brand attitude. Interestingly, this effect was only found when attitudinal advertising literacy was assessed with a questionnaire and not when it was assessed with the indirect measurement task. Thus, children who were more critical toward the in-vlog advertisement through self-reporting also had a more negative brand attitude. This suggests that direct and indirect measurements of advertising literacy activation reveal different processes through which children make sense of, and are affected by, advertising.

The self-generated full body illusion is accompanied by impaired detection of somatosensory stimuli.

Research has found that body illusions may be accompanied by consequences for the real body whereby various somatosensory and homeostatic bodily functions may be impaired. These findings stem from research where an experimenter induced the body illusions. In line with advances in the domains of videogames and virtual reality where the real body is used as a controller we investigate if these consequences also accompany self-generated body illusions. In two preregistered experiments we made use of a head-mounted display set-up to induce the full body illusion (FBI) whereby touch is felt to originate from a 3PP body, and examined effects in the simple detection of supra-threshold vibrotactile stimuli presented to the participants' back and head. Results of both experiments indicate that it is possible to induce a FBI through self-stroking of the neck and that the FBI is accompanied by reduced accuracy and delayed reaction times in detection of somatosensory stimuli. In an additional preregistered control experiment the alternative explanation that a difference in motion presented in the conditions was responsible for these findings was ruled out. Our findings corroborate previous studies that have found body illusions to be accompanied by bodily consequences and further extend these findings to the domain of self-induced body illusions. These results are relevant for video games and VR setups that are geared towards virtual embodiment as they advance our understanding of the conditions and mechanisms in which bodily consequences may express themselves.

The clinical suspicion of a leaking intrathoracic esophagogastric anastomosis: the role of CT imaging.

BACKGROUND: CT imaging is the primary diagnostic approach to assess the integrity of the intrathoracic anastomosis following Ivor Lewis esophagectomy. In the postoperative setting interpretation of CT findings, such as air and fluid collections, may be challenging. Establishment of a scoring system that incorporates CT findings to diagnose anastomotic leakage could assist radiologists and surgeons in the postoperative phase. METHODS: Consecutive patients who underwent a CT scan for a clinical suspicion of postoperative anastomotic leakage following Ivor Lewis esophagectomy between 2010 and 2016 in two medical centers were retrospectively included. Scans were excluded when oral contrast was not (correctly) administered. Acquired images were randomized and independently assessed by two experienced gastrointestinal radiologists, blinded for clinical information. For this study anastomotic leakage was defined as a visible defect during endoscopy or thoracotomy. RESULTS: A total of 80 patients had 101 CT scans, resulting in 32 scans with a confirmed anastomotic leak (25 patients). After multivariable backward stepwise logistic regression, a practical 5-point scoring system was developed, which included the following CT findings: presence of extraluminal oral contrast, air collection at the anastomotic site, fluid collection at the anastomotic site, pneumothorax and loculated pleural effusion. Patients with a score of ≥3 were considered at high risk for anastomotic leakage (positive predictive value: 83.3%), patients with scores <3 were considered at low risk for anastomotic leakage (negative predictive value: 84.4%). The scoring system showed a superior diagnostic performance compared to the original CT report and blinded interpretation of two radiologists. CONCLUSIONS: Our CT-based practical scoring system enables a standardized approach in CT assessment and could facilitate early recognition of anastomotic leakage in patients after Ivor Lewis esophagectomy.

Is mindfulness associated with interpersonal forgiveness?

Using a multimethod approach, the current research tested the basic prediction that mindfulness is associated with interpersonal forgiveness. Across 5 studies, we found that mindfulness meditation, trait mindfulness, and an experimental induction of mindfulness, were positively associated with indicators of both dispositional forgiving tendencies, state levels of forgiveness regarding a past offense, and levels of perceived forgiving tendencies as rated by the romantic partner. Two studies examined the roles of perspective taking and rumination as potential mechanisms; results provided most consistent support for the role of perspective taking. The findings are discussed in light of the broader theoretical questions of when and how people forgive and how mindfulness may promote interpersonal functioning. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Activation of Mirror Neuron Regions Is Altered in Developmental Coordination Disorder (DCD)-Neurophysiological Evidence Using an Action Observation Paradigm.

Children with Developmental Coordination Disorder (DCD) have difficulty performing and learning motor skills. Automatic activation of the mirror neuron system (MNS) during action observation and its coupling to the motor output system are important neurophysiological processes that underpin observational motor learning. In the present study, we tested the hypothesis that MNS function is disrupted in children with DCD by using sensitive electroencephalography (EEG)-based measures of MNS activation during action observation. Specifically, we predicted reduced mu-suppression and coherence in DCD compared with typically developing children. Neural activation of the motor network was measured by EEG, specifically event-related desynchronization (ERD) of mu rhythms and fronto-parietal coherence. Children (15 DCD/15 controls) were tested under two task conditions: observational learning (imitation of an observed action) and detection (report a deviant movement after observation). EEG-metrics were compared between groups using linear mixed-effects models. As predicted, children with DCD showed lower levels of mu suppression and reduced modulation of coherence during the observational learning task compared with their non-DCD peers. Notably, mu suppression was reduced in DCD over the entire imitation task (repetitions, and both observation and pause intervals). Action observation can be used for the acquisition of new motor skills. This form of learning entails the transposition of the observed action to the existing internal representations of the observer's own motor system. The present neurophysiological results suggest that this process of learning is impaired in children with DCD. The results are discussed in relation to current hypotheses on mechanisms of DCD.

The neural correlates of the awe experience: Reduced default mode network activity during feelings of awe.

In the present fMRI study, we aimed to obtain insight into the key brain networks involved in the experience of awe-a complex emotion that is typically elicited by perceptually vast stimuli. Participants were presented with awe-eliciting, positive and neutral videos, while they were instructed to get fully absorbed in the scenery or to count the number of perspective changes. By using a whole-brain analysis we found that several brain regions that are considered part of the default mode network (DMN), including the frontal pole, the angular gyrus, and the posterior cingulate cortex, were more strongly activated in the absorption condition. But this was less the case when participants were watching awe videos. We suggest that while watching awe videos, participants were deeply immersed in the videos and that levels of self-reflective thought were as much reduced during the awe videos, as during the perspective counting condition. In contrast, key regions of the fronto-parietal network (FPN), including the supramarginal gyrus, the medial frontal gyrus, and the insula, were most strongly activated in the analytical condition when participants were watching awe compared to positive and neutral videos. This finding underlines the captivating, immersive, and attention-grabbing nature of awe stimuli that is considered to be responsible for reductions in self-reflective thought. Together these findings suggest that a key feature of the experience of awe is a reduced engagement in self-referential processing, in line with the subjective self-report measures (i.e., participants perceived their self to be smaller).

Renal imaging in 199 Dutch patients with Birt-Hogg-Dubé syndrome: Screening compliance and outcome.

Birt-Hogg-Dubé syndrome is associated with an increased risk for renal cell carcinoma. Surveillance is recommended, but the optimal imaging method and screening interval remain to be defined. The main aim of our study was to evaluate the outcomes of RCC surveillance to get insight in the safety of annual US in these patients. Surveillance data and medical records of 199 patients with Birt-Hogg-Dubé syndrome were collected retrospectively using medical files and a questionnaire. These patients were diagnosed in two Dutch hospitals and data were collected until June 2014. A first screening for renal cell carcinoma was performed in 172/199 patients (86%). Follow-up data were available from 121 patients. The mean follow-up period per patient was 4.2 years. Of the patients known to be under surveillance, 83% was screened at least annually and 94% at least every two years. Thirty-eight renal cell carcinomas had occurred in 23 patients. The mean age at diagnosis of the first tumour was 51. Eighteen tumours were visualized by ultrasound. Nine small tumours (7-27 mm) were visible on MRI or CT and not detected using ultrasound. Our data indicate that compliance to renal screening is relatively high. Furthermore, ultrasound might be a sensitive, cheap and widely available alternative for MRI or part of the MRIs for detecting clinically relevant renal tumours in BHD patients,but the limitations should be considered carefully. Data from larger cohorts are necessary to confirm these observations.

Application of a worry reduction intervention in a medically unexplained symptoms-analogue student-sample.

OBJECTIVE: Worry is an important perpetuating factor of Medically Unexplained Symptoms (MUS). Former research has shown that a worry postponement instruction is effective in reducing Subjective Health Complaints (SHC) in non-clinical samples. This study aimed to (1) replicate these findings in a MUS-analogue student-sample and (2) assess alexithymia as a moderator. DESIGN: The current study had an experimental design with two waves of data collection: pre- and post-intervention. MAIN OUTCOME MEASURES: A MUS-analogue student-sample consisting of 114 undergraduate students with high self-reported health worry and a minimum of two doctor visits in the previous year with no current diagnosis for a (chronic or acute) disease were instructed to register their worry frequency and duration eight times per day via an experience sampling-application on their smartphones. The intervention group additionally postponed their worries to a 30-minute period in the evening. SHC were assessed pre- and post-intervention. RESULTS: The intervention did not have an effect on worry or SHC. Alexithymia did not moderate this effect (p's > .05). CONCLUSION: Our study did not find evidence for the effectiveness of the worry reduction intervention on SHC in a MUS-analogue student-sample. This finding contributes to several previous studies that have found mixed evidence for the effectiveness of the worry reduction intervention on SHC and suggests that the worry intervention may not be effective in all cases.