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Despite good intentions, people often fail to cross the “intention–behavior gap,” especially when goal achievement requires repeated action. To bridge this gap, the formation of automatized routines may be crucial. However, people may differ in the tendency to switch from goal-directed toward habitual control. To shed light on why some people succeed in forming routines while others struggle, the present study related the automatization of a novel, daily routine to individual differences in white-matter connectivity in corticostriatal networks that have been implicated in goal-directed and habitual control. Seventy-seven participants underwent diffusion-weighted imaging and formed the daily routine of taking a (placebo) pill for 3 weeks. Pill intake was measured by electronic pill boxes, and participants filled out a daily online questionnaire on the subjective automaticity of this behavior. Automatization of pill intake was negatively related to striatal (mainly caudate) connectivity with frontal goal-directed and cognitive control regions, namely, ventromedial pFC and anterior cingulate gyrus. Furthermore, daily pill intake was positively related to individual differences in striatal (mainly caudate) connectivity with cognitive control regions, including dorsolateral and anterior pFC. Therefore, strong control networks may be relevant for implementing a new routine but may not benefit its automatization. We also show that habit tendency (assessed with an outcome-devaluation task), conscientiousness, and daily life regularity were positively related to routine automatization. This translational study moves the field of habit research forward by relating self-reported routine automatization to individual differences in performance on an experimental habit measure and to brain connectivity.

People often have good intentions but fail to adhere to them. Implementation intentions, a form of strategic planning, can help people to close this intention–behavior gap. Their effectiveness has been proposed to depend on the mental formation of a stimulus–response association between a trigger and target behavior, thereby creating an “instant habit.” If implementation intentions do indeed lead to reliance on habitual control, then this may come at the cost of reduced behavioral flexibility. Furthermore, we would expect a shift from recruitment of corticostriatal brain regions implicated in goal-directed control toward habit regions. To test these ideas, we performed a fMRI study in which participants received instrumental training supported by either implementation or goal intentions, followed by an outcome revaluation to test reliance on habitual versus goal-directed control. We found that implementation intentions led to increased efficiency early in training, as reflected by higher accuracy, faster RTs, and decreased anterior caudate engagement. However, implementation intentions did not reduce behavioral flexibility when goals changed during the test phase, nor did it affect the underlying corticostriatal pathways. In addition, this study showed that “slips of action” toward devalued outcomes are associated with reduced activity in brain regions implicated in goal-directed control (ventromedial prefrontal cortex and lateral orbitofrontal cortex) and increased activity of the fronto-parietal salience network (including the insula, dorsal anterior cingulate cortex, and SMA). In conclusion, our behavioral and neuroimaging findings suggest that strategic if–then planning does not lead to a shift from goal-directed toward habitual control.

The differential impact of rural versus urban residence on mental health remains a controversial topic that requires more in-depth investigations. This calls for a valid and easy measure to assess the degree of urbanisation. The purpose of the present study was to determine the utility of a single-item self-report measure (SIDU) as a tool to classify areas along the rural-urban continuum. The validity of the SIDU was assessed by comparing its scores (1–7) to a commonly used objective surrogate measure of the degree of urbanisation (i.e. surrounding address density, SAD) in two independent older adult samples (A: N = 36, 65+; B: N = 121, 55+). SIDU scores approximated SAD scores, with r = .77 to 0.82, (A), and r = .79 to 0.83 (B). A SIDU threshold score of 6 most accurately distinguished extremely urbanised areas from other areas. Altogether, our findings suggest that SIDU scores could be used as proxy of SAD. Since self-report leaves room for the consideration of additional aspects that confer an urban settlement, this single-item scale may be even more comprehensive, and circumvents the collection and handling of highly sensitive location data when the primary goal is solely to distinguish urbanisation subgroups.

Within the aging population, the frequency of cancer is increasing dramatically. In addition, multiple genetic and environmental factors lead to common multifactorial diseases, including cardiovascular disease, chronic kidney disease, chronic obstructive pulmonary disease, and metabolic-associated fatty liver disease. In recent years, there has been a growing awareness of the connection between cancer and multifactorial diseases, as well as how one can affect the other, resulting in a vicious cycle. Although the exact mechanistic explanations behind this remain to be fully explored, some progress has been made in uncovering the common pathologic mechanisms. In this review, we focus on the nature of the link between cancer and common multifactorial conditions, as well as specific shared mechanisms, some of which may represent either preventive or therapeutic targets. Rather than organ-specific interactions, we herein focus on the shared mechanisms among the multifactorial diseases, which may explain the increased cancer risk. More research on this subject will highlight the significance of developing new drugs that target multiple systems rather than just one disease.

Contains fulltext : 291058.pdf (Publisher’s version ) (Open Access) AIM: We aimed to analyse the association of clonal haematopoiesis of indeterminate potential (CHIP) with incident heart failure (HF) in a European population cohort. METHODS AND RESULTS: From the prospective Prevention of Renal and Vascular End-stage Disease (PREVEND) cohort, we included all 374 participants with incident HF and selected 1:1 age- and sex-matched control subjects. Peripheral blood samples of 705 individuals were successfully analysed by error-corrected next generation sequencing for acquired mutations at a variant allele frequency ≥2% in 27 CHIP driver genes. The median age of the study population was 65 years (interquartile range 58-70) and 35.6% were female. CHIP mutations positively correlated with age, smoking, hypertension and cardiovascular biomarkers including N-terminal pro-B-type natriuretic peptide and mid-regional pro-A-type natriuretic peptide, but the frequency of CHIP was comparable in individuals with incident HF and in control participants (18.4% vs. 17.3%; p = 0.69). In multivariable Cox regression models, CHIP was not significantly associated with incident HF (hazard ratio [HR] 1.24, 95% confidence interval [CI] 0.93-1.65; p = 0.144). This association, however, was modified by age (p for CHIP-age interaction = 0.002). Among people younger than 65 years, CHIP mutations were more frequently detected in the case cohort compared to the control cohort (14.2% vs. 5.8%; p = 0.009), and were significantly associated with new-onset HF (HR 2.07, 95% CI 1.30-3.29; p = 0.002). CONCLUSION: Clonal haematopoiesis of indeterminate potential correlates with HF risk factors and biomarkers, and is associated with incident HF in subjects

Heart failure (HF) and cancer are the leading causes of death worldwide and accumulating evidence demonstrates that HF and cancer affect one another in a bidirectional way. Patients with HF are at increased risk for developing cancer, and HF is associated with accelerated tumour growth. The presence of malignancy may induce systemic metabolic, inflammatory, and microbial alterations resulting in impaired cardiac function. In addition to pathophysiologic mechanisms that are shared between cancer and HF, overlaps also exist between pathways required for normal cardiac physiology and for tumour growth. Therefore, these overlaps may also explain the increased risk for cardiotoxicity and HF as a result of targeted anti-cancer therapies. This review provides an overview of mechanisms involved in the bidirectional connection between HF and cancer, specifically focusing upon current ‘hot-topics’ in these shared mechanisms. It subsequently describes targeted anti-cancer therapies with cardiotoxic potential as a result of overlap between their anti-cancer targets and pathways required for normal cardiac function.

International audience; Aims Insulin like growth factor binding protein 7 (IGFBP7) is a marker of senescence secretome and a novel biomarker in patients with heart failure (HF). We evaluated the prognostic value of IGFBP7 in patients with heart failure and examined associations to uncover potential new pathophysiological pathways related to increased plasma IGFBP7 concentrations. Methods and results We have measured plasma IGFBP7 concentrations in 2250 subjects with new-onset or worsening heart failure (BIOSTAT-CHF cohort). Higher IGFBP7 plasma concentrations were found in older subjects, those with worse kidney function, history of atrial fibrillation, and diabetes mellitus type 2, and in subjects with higher number of HF hospitalizations. Higher IGFBP7 levels also correlate with the levels of several circulating biomarkers, including higher NT-proBNP, hsTnT, and urea levels. Cox regression analyses showed that higher plasma IGFBP7 concentrations were strongly associated with increased risk of all three main endpoints (hospitalization, all-cause mortality, and combined hospitalization and mortality) (HR 1.75, 95% CI 1.25-2.46; HR 1.71, 95% CI 1.39-2.11; and HR 1.44, 95% CI 1.23-1.70, respectively). IGFBP7 remained a significant predictor of these endpoints in patients with both reduced and preserved ejection fraction. Likelihood ratio test showed significant improvement of all three risk prediction models, after adding IGFBP7 (P < 0.001). A biomarker network analysis showed that IGFBP7 levels activate different pathways involved in the regulation of the immune system. Results were externally validated in BIOSTAT-CHF validation cohort. Conclusions IGFPB7 presents as an independent and robust prognostic biomarker in patients with HF, with both reduced and preserved ejection fraction. We validate the previously published data showing IGFBP7 has correlations with a number of echocardiographic markers. Lastly, IGFBP7 pathways are involved in different stages of immune system regulation, linking heart failure to senescence pathways.

Implementation intentions (strategic “if-then” plans) have been shown to support behaviour change. This may be achieved by mentally forming stimulus-response associations, thereby promoting habit formation. Does this deliberate attempt to instal “strategic automaticity” only offer advantages, or does it also come at the cost of reduced flexibility that characterises learnt habits? To investigate this, we tested healthy, young participants on a computerised instrumental learning task. Critically, we introduced implementation intentions (“if I see stimulus X, then I will respond”) versus goal intentions (“for outcome Z, I will respond)” during instrumental acquisition, and subsequently assessed behavioural flexibility in an outcome-revaluation test. In Experiment 1, we conducted a between-subjects manipulation of strategic planning, and in Experiment 2, a within-subject manipulation. We hypothesised that implementation intentions would lead to strong stimulus-response associations and consequently impair performance when the signalled outcome value changed and therefore required a different response, while benefitting performance when the outcome value (and required response) remained the same. We found that implementation intentions supported instrumental learning, but impaired test performance overall (most robustly in Experiment 2), irrespective of whether the signalled outcome value had changed. We argue that this general detrimental effect of implementation intentions on test performance is likely a consequence of their negative effect on stimulus-outcome learning. Our findings warrant caution when applying if-then plans to situations where the agent does not already possess perfect knowledge of behavioural contingencies.While implementation intentions may support efficient and fast behavioural execution, this may come at the expense of behavioural flexibility.

Despite our familiarity with the concept of habits, eliciting and measuring habits experimentally in humans has proven to be difficult. A possible explanation is that participants in psychological experiments actively recruit goal-directed control and therefore make few habitual slips-of-action in the presence of stimuli signalling devalued outcomes. In the current experiment we used the symmetrical outcome-revaluation task in combination with a working memory load in an attempt to tip the balance from goal-directed control to stimulus-response habit. During the instrumental learning phase, participants learned to make a Go response to stimuli signalling valuable outcomes (and points) while not responding (NoGo) to stimuli signalling not-valuable outcomes. During the subsequent test phase, the outcomes signalled by the stimuli were either value-congruent with training (still-valuable and still-not-valuable), or value-incongruent (devalued and upvalued). Participants had to flexibly adjust their behaviour on value-incongruent trials where the stimulus-response association learned during training was no longer appropriate. For half the participants, a concurrent working memory load was imposed during the test phase. In line with our preregistered hypotheses, participants showed evidence for habitual slips-of-action but those under working memory load showed increased habit tendencies (specifically failures to inhibit prepotent Go responses in the presence of stimuli signalling devalued outcomes). This central finding suggests that a working memory load can be used to reveal habits in humans.

Background: Heart failure (HF) is the leading cause of morbidity and mortality worldwide, and there is an urgent need for more global studies and data mining approaches to uncover its underlying mechanisms. Multiple omics techniques provide a more holistic molecular perspective to study pathophysiological events involved in the development of HF. Methods: In this study, we used a label-free whole myocardium multi-omics characterization from three commonly used mouse HF models: transverse aortic constriction (TAC), myocardial infarction (MI), and homozygous Phospholamban-R14del (PLN-R14Δ/Δ). Genes, proteins, and metabolites were analysed for differential expression between each group and a corresponding control group. The core transcriptome and proteome datasets were used for enrichment analysis. For genes that were upregulated at both the RNA and protein levels in all models, clinical validation was performed by means of plasma level determination in patients with HF from the BIOSTAT-CHF cohort. Results: Cell death and tissue repair-related pathways were upregulated in all preclinical models. Fatty acid oxidation, ATP metabolism, and Energy derivation processes were downregulated in all investigated HF aetiologies. Putrescine, a metabolite known for its role in cell survival and apoptosis, demonstrated a 4.9-fold (p < 0.02) increase in PLN-R14Δ/Δ, 2.7-fold (p < 0.005) increase in TAC mice, and 2.2-fold (p < 0.02) increase in MI mice. Four Biomarkers were associated with all-cause mortality (PRELP: Hazard ratio (95% confidence interval) 1.79(1.35, 2.39), p < 0.001; CKAP4: 1.38(1.21, 1.57), p < 0.001; S100A11: 1.37(1.13, 1.65), p = 0.001; Annexin A1 (ANXA1): 1.16(1.04, 1.29) p = 0.01), and three biomarkers were associated with HF-Related Rehospitalization, (PRELP: 1.88(1.4, 2.53), p < 0.001; CSTB: 1.15(1.05, 1.27), p = 0.003; CKAP4: 1.18(1.02, 1.35), P = 0.023). Conclusions: Cell death and tissue repair pathways were significantly upregulated, and ATP and energy derivation processes were significantly downregulated in all models. Common pathways and biomarkers with potential clinical and prognostic associations merit further investigation to develop optimal management and therapeutic strategies for all HF aetiologies.

Ageism as perceived by older individuals has been recognized as a potential risk factor for physical and mental health. We aimed to develop a comprehensive scale that can quantify perceived ageism among aging individuals (55+), including both positive and negative stereotypes, prejudices, and discriminations. This effort resulted in an 8-item Perceived Ageism Questionnaire (PAQ-8), with good psychometric properties and a two-factor structure distinguishing a positive (3 items) and negative (5 items) subscale (Analysis 1; n = 500). This dimensionality was confirmed in a separate cross-validation sample (Analysis 2; n = 500). The subscales' correlation patterns with individuals' self-perceptions of aging and mental health variables (i.e., quality of life, mental well-being, depression, anxiety, loneliness and perceived stress) accorded with theoretical hypotheses and existing knowledge of the concept of ageism. The PAQ-8 can help to gather more standardized data of the level, role and impact of perceived ageism.

Recent models of bulimia nervosa (BN) propose that binge-purge episodes ultimately become automatic in response to cues and insensitive to negative outcomes. Here, we examined whether women with BN show alterations in instrumental learning and devaluation sensitivity using traditional and computational modeling analyses of behavioral data. Adult women with BN (n = 30) and group-matched healthy controls (n = 31) completed a task in which they first learned stimulus-response-outcome associations. Then, participants were required to repeatedly adjust their responses in a "baseline test", when different sets of stimuli were explicitly devalued, and in a "slips-of-action test", when outcomes instead of stimuli were devalued. The BN group showed intact behavioral sensitivity to outcome devaluation during the slips-of-action test, but showed difficulty overriding previously learned stimulus-response associations on the baseline test. Results from a Bayesian learner model indicated that this impaired performance could be accounted for by a slower pace of belief updating when a new set of previously learned responses had to be inhibited (p = 0.036). Worse performance and a slower belief update in the baseline test were each associated with more frequent binge eating (p = 0.012) and purging (p = 0.002). Our findings suggest that BN diagnosis and severity are associated with deficits in flexibly updating beliefs to withhold previously learned responses to cues. Additional research is needed to determine whether this impaired ability to adjust behavior is responsible for maintaining automatic and persistent binge eating and purging in response to internal and environmental cues.

The translation of the outcome-devaluation paradigm to study habit in humans has yielded interesting insights but proven to be challenging. We present a novel, outcome-revaluation task with a symmetrical design, in the sense that half of the available outcomes are always valuable and the other half not-valuable. In the present studies, during the instrumental learning phase, participants learned to respond (Go) to certain stimuli to collect valuable outcomes (and points) while refraining to respond (NoGo) to stimuli signalling not-valuable outcomes. Half of the stimuli were short-trained, while the other half were long-trained. Subsequently, in the test phase, the signalled outcomes were either value-congruent with training (still-valuable and still-not-valuable), or value-incongruent (devalued and upvalued). The change in outcome value on value-incongruent trials meant that participants had to flexibly adjust their behaviour. At the end of the training phase, participants completed the self-report behavioural automaticity index – providing an automaticity score for each stimulus-response association. We conducted two experiments using this task, that both provided evidence for stimulus-driven habits as reflected in poorer performance on devalued and upvalued trials relative to still-not-valuable trials and still-valuable trials, respectively. While self-reported automaticity increased with longer training, behavioural flexibility was not affected. After extended training (Experiment 2), higher levels of self-reported automaticity when responding to stimuli signalling valuable outcomes were related to more ‘slips of action’ when the associated outcome was subsequently devalued. We conclude that the symmetrical outcome-revaluation task provides a promising paradigm for the experimental investigation of habits in humans.

Food choices are influenced by one's current mindset, suggesting that supporting health (vs. a palatability) mindsets could improve daily food choices. The question rises, however, to what extent internal mindsets still guide choices when people are exposed to external food-context stimuli in an obesogenic environment. To examine these two competing effects we induced health vs. palatability mindsets, and investigated the robustness of the mindset effect by presenting food-context stimuli during a Pavlovian-to-Instrumental-Transfer (PIT) task in two separate cohorts of 102 (76 females) Dutch and 120 (60 females) German participants. For the mindset induction, participants rated food items on visual analogue scales (VAS), based on healthiness and palatability, respectively. In each cohort, half of the participants received a health, the other half a palatability mindset induction. Additionally, we explored whether ‘mindset triggers’ could be used to further shape behavior. Triggers were established by placing unfamiliar logos at the extreme ends of the VASs used for the mindset inductions.Independent of the mindset, food-associated stimuli influenced food choices in accordance with the previously learned association in each test phase. Health mindset induction biased food choices towards healthier, palatability mindset towards unhealthier choices in the first cohort, but not in the second. The mindset triggers had a more robust effect. These induced healthier (triggers for healthy and not-palatable) and unhealthier (triggers for unhealthy and palatable) food choices in both cohorts alike. Interestingly, these effects did not tamper with the overall effect of Pavlovian cues and were thus true in the presence and absence of food-context stimuli. Therefore, we show that, in our experimental setting, food-associated mindset triggers can be used to bias food choices towards a healthy snack even in an obesogenic environment.

In the wake of the COVID-19 pandemic, physical distancing behavior turned out to be key to mitigating the virus spread. Therefore, it is crucial that we understand how we can successfully alter our behavior and promote physical distancing. We present a framework to systematically assess the effectiveness of behavioral interventions to stimulate physical distancing. In addition, we demonstrate the feasibility of this framework in a large-scale natural experiment (N = 639) conducted during an art fair. In an experimental design, we varied interventions to evaluate the effect of face masks, walking directions, and immediate feedback on visitors’ contacts. We represent visitors as nodes, and their contacts as links in a contact network. Subsequently, we used network modelling to test for differences in these contact networks. We find no evidence that face masks influence physical distancing, while unidirectional walking directions and buzzer feedback do positively impact physical distancing. This study offers a feasible way to optimize physical distancing interventions through scientific research. As such, the presented framework provides society with the means to directly evaluate interventions, so that policy can be based on evidence rather than conjecture.

In the absence of a vaccine, social distancing behaviour is pivotal to mitigate COVID-19 virus spread. In this large-scale behavioural experiment, we gathered data during Smart Distance Lab: The Art Fair (n = 839) between August 28 and 30, 2020 in Amsterdam, the Netherlands. We varied walking directions (bidirectional, unidirectional, and no directions) and supplementary interventions (face mask and buzzer to alert visitors of 1.5 metres distance). We captured visitors’ movements using cameras, registered their contacts (defined as within 1.5 metres) using wearable sensors, and assessed their attitudes toward COVID-19 as well as their experience during the event using questionnaires. We also registered environmental measures (e.g., humidity). In this paper, we describe this unprecedented, multi-modal experimental data set on social distancing, including psychological, behavioural, and environmental measures. The data set is available on figshare and in a MySQL database. It can be used to gain insight into (attitudes toward) behavioural interventions promoting social distancing, to calibrate pedestrian models, and to inform new studies on behavioural interventions., Measurement(s) Proximity • Movement • Attitudes and beliefs relating to COVID-19 • Indoor environment measures Technology Type(s) Ultra-wideband technology • Camera Device • questionnaire • environment sensor Factor Type(s) Walking direction • Wearing of face masks • Proximity buzzer Sample Characteristic - Organism Homo sapiens Sample Characteristic - Environment public exhibition Sample Characteristic - Location Kingdom of the Netherlands Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.14312180

The need for a liquid biopsy in non-small cell lung cancer (NSCLC) patients is rapidly increasing. We studied the relation between overall survival (OS) and the presence of four cancer biomarkers from a single blood draw in advanced NSCLC patients: EpCAM(high) circulating tumor cells (CTC), EpCAM(low) CTC, tumor-derived extracellular vesicles (tdEV) and cell-free circulating tumor DNA (ctDNA). EpCAM(high) CTC were detected with CellSearch, tdEV in the CellSearch images and EpCAM(low) CTC with filtration after CellSearch. ctDNA was isolated from plasma and mutations present in the primary tumor were tracked with deep sequencing methods. In 97 patients, 21% had >= 2 EpCAM(high) CTC, 15% had >= 2 EpCAM(low) CTC, 27% had >= 18 tdEV and 19% had ctDNA with >= 10% mutant allele frequency. Either one of these four biomarkers could be detected in 45% of the patients and all biomarkers were present in 2%. In 11 out of 16 patients (69%) mutations were detected in the ctDNA. Two or more unfavorable biomarkers were associated with poor OS. The presence of EpCAM(high) CTC and elevated levels of tdEV and ctDNA was associated with a poor OS; however, the presence of EpCAM(low) CTC was not. This single tube approach enables simultaneous analysis of multiple biomarkers to explore their potential as a liquid biopsy.

Neonatal hyperbilirubinemia or jaundice is associated with kernicterus, resulting in permanent neurological damage or even death. Conventional phototherapy does not prevent hyperbilirubinemia or eliminate the need for exchange transfusion. Here we investigated the potential of therapeutic bile acids ursodeoxycholic acid (UDCA) and obeticholic acid (OCA, 6-α-ethyl-CDCA), a farnesoid-X-receptor (FXR) agonist, as preventive treatment options for neonatal hyperbilirubinemia using the hUGT1*1 humanized mice and Ugt1a-deficient Gunn rats. Treatment of hUGT1*1 mice with UDCA or OCA at postnatal days 10–14 effectively decreased bilirubin in plasma (by 82% and 62%) and brain (by 72% and 69%), respectively. Mechanistically, our findings indicate that these effects are mediated through induction of protein levels of hUGT1A1 in the intestine, but not in liver. We further demonstrate that in Ugt1a-deficient Gunn rats, UDCA but not OCA significantly decreases plasma bilirubin, indicating that at least some of the hypobilirubinemic effects of UDCA are independent of UGT1A1. Finally, using the synthetic, non-bile acid, FXR-agonist GW4064, we show that some of these effects are mediated through direct or indirect activation of FXR. Together, our study shows that therapeutic bile acids UDCA and OCA effectively reduce both plasma and brain bilirubin, highlighting their potential in the treatment of neonatal hyperbilirubinemia.

In the absence of a vaccine, social distancing behaviour is pivotal to mitigate COVID-19 virus spread. In this large-scale behavioural experiment, we gathered data during Smart Distance Lab: The Art Fair (n = 787) between August 28 and 30, 2020 in Amsterdam, the Netherlands. We varied walking directions (bidirectional, unidirectional, and no directions) and supplementary interventions (face mask and buzzer to alert visitors of 1.5 metres distance). We captured visitors' movements using cameras, registered their contacts (defined as within 1.5 metres) using wearable sensors, and assessed their attitudes toward COVID-19 as well as their experience during the event using questionnaires. We also registered environmental measures (e.g., humidity). In this paper, we describe this unprecedented, multi-modal experimental data set on social distancing, including psychological, behavioural, and environmental measures. The data set is available on Figshare and in a MySQL database. It can be used to gain insight into (attitudes toward) behavioural interventions promoting social distancing, to calibrate pedestrian models, and to inform new studies on behavioural interventions.

In the wake of the COVID-19 pandemic, the central importance of human behaviour in mitigating the spread of the virus has become universally recognized. We present a methodology to systematically assess the effectiveness of behavioural interventions to stimulate social distancing. In addition, we demonstrate the feasibility of this framework in a large-scale natural experiment. In an experimental design, we varied behavioural interventions to evaluate the effect of face masks, walking directions, and immediate feedback on visitors’ contacts. We represent visitors as nodes, and their contacts as links in a contact network. Subsequently, we used network modelling to test for differences in these contact networks. We find no evidence that face masks influence social distancing, while unidirectional walking directions and buzzer feedback do positively impact social distancing. The presented methodology represents a practically feasible way to optimize social distancing interventions through scientific research and may directly inform policy.

Circulating tumour cells (CTCs) found in the blood of cancer patients are a promising biomarker in precision medicine. However, their use is currently hindered by their low frequency, tedious manual scoring and extensive cell heterogeneities. Those challenges limit the effectiveness of classical machine-learning methods for automated CTC analysis. Here, we combine autoencoding convolutional neural networks with advanced visualization techniques. This provides a very informative view on the data that opens the way for new biomedical research questions. We unravel hidden information in the raw image data of fluorescent images of blood samples enriched for CTCs. Our network classifies fluorescent images of single cells in five different classes with an accuracy, sensitivity and specificity of over 96%, and the obtained CTC counts predict the overall survival of cancer patients as well as state-of-the-art manual counts. Moreover, our network excelled in identifying different important subclasses of objects. Deep learning was faster and superior to classical image analysis approaches and enabled the identification of new biological phenomena. Counting different types of circulating tumour cells can give valuable information on the severity of the disease and on whether treatments are effective for a specific patient. In this work, the authors show that their method based on autoencoders can identify and count cells more accurately and faster than human experts.

Introduction Harmful behavior such as smoking may reflect a disturbance in the balance of goal-directed and habitual control. Animal models suggest that habitual control develops after prolonged substance use. In this study, we investigated whether smokers (N = 49) differ from controls (N = 46) in the regulation of goal-directed and habitual behavior. It was also investigated whether individual differences in nicotine dependence levels were associated with habitual responding. Methods We used two different multistage instrumental learning tasks that consist of an instrumental learning phase, subsequent outcome devaluation, and a testing phase to measure the balance between goal-directed and habitual responding. The testing phases of these tasks occurred after either appetitive versus avoidance instrumental learning. The appetitive versus aversive instrumental learning stages in the two different tasks modeled positive versus negative reinforcement, respectively. Results Smokers and nonsmoking controls did not differ on habitual versus goal-directed control in either task. Individual differences in nicotine dependence within the group of smokers, however, were positively associated with habitual responding after appetitive instrumental learning. This effect seems to be due to impaired stimulus-outcome learning, thereby hampering goal-directed task performance and tipping the balance to habitual responding. Conclusions The current finding highlights the importance of individual differences within smokers. For future research, neuroimaging studies are suggested to further unravel the nature of the imbalance between goal-directed versus habitual control in severely dependent smokers by directly measuring activity in the corresponding brain systems. Implications Goal-directed versus habitual behavior in substance use and addiction is highly debated. This study investigated goal-directed versus habitual control in smokers. The findings suggest that smokers do not differ from controls in goal-directed versus habitual control. Individual differences in nicotine dependence within smokers, however, were positively associated with habitual responding after appetitive instrumental learning. This effect seems to be due to impaired stimulus-outcome learning, thereby hampering goal-directed task performance and tipping the balance to habitual responding. These findings add to the ongoing debate on habitual versus goal-directed control in addiction and emphasize the importance of individual differences within smokers.

Background Circulating tumour cells (CTCs) in blood associate with overall survival (OS) of cancer patients, but they are detected in extremely low numbers. Large tumour-derived extracellular vesicles (tdEVs) in castration-resistant prostate cancer (CRPC) patients are present at around 20 times higher frequencies than CTCs and have equivalent prognostic power. In this study, we explored the presence of tdEVs in other cancers and their association with OS. Methods The open-source ACCEPT software was used to automatically enumerate tdEVs in digitally stored CellSearch® images obtained from previously reported CTC studies evaluating OS in 190 CRPC, 450 metastatic colorectal cancer (mCRC), 179 metastatic breast cancer (MBC) and 137 non-small cell lung cancer (NSCLC) patients before the initiation of a new treatment. Results Presence of unfavourable CTCs and tdEVs is predictive of OS, with respective hazard ratios (HRs) of 2.4 and 2.2 in CRPC, 2.7 and 2.2 in MBC, 2.3 and 1.9 in mCRC and 2.0 and 2.4 in NSCLC, respectively. Conclusions tdEVs have equivalent prognostic value as CTCs in the investigated metastatic cancers. CRPC, mCRC, and MBC (but not NSCLC) patients with favourable CTC counts can be further prognostically stratified using tdEVs. Our data suggest that tdEVs could be used in clinical decision-making.

For using counts of circulating tumor cells (CTCs) in the clinic to aid a physician's decision, its reported values will need to be accurate and comparable between institutions. Many technologies have become available to enumerate and characterize CTCs, thereby showing a large range of reported values. Here we introduce an Open Source CTC scoring tool to enable comparison of different reviewers and facilitate the reach of a consensus on assigning objects as CTCs. One hundred images generated from two different platforms were used to assess concordance between 15 reviewers and an expert panel. Large differences were observed between reviewers in assigning objects as CTCs urging the need for computer recognition of CTCs. A demonstration of a deep learning approach on the 100 images showed the promise of this technique for future CTC enumeration. © 2018 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.

Background: It is unknown whether the presence of circulating tumor cells (CTC), a known prognostic factor, influences treatment outcome. We investigated whether baseline CTC in non-small cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitors (TKI) or chemotherapy was associated with response to therapy. Methods: We included consecutive advanced NSCLC patients, stratified by therapy. Before treatment the number of CTC was measured by CellSearch. Tumor response rates, progression free survival (PFS) and overall survival (OS) in patients with and without CTC at baseline were compared. Results: We included 86 patients (34 treated by TKI). Response rates of patients with CTC were lower than in patients without CTC (OR =0.22, P

The interplay between inflexible habits and flexible goal-directed control can be modelled in lab-settings using the slips-of-action task. In this task, participants are required to selectively respond to still-valuable outcomes while suppressing responding towards no-longer valuable outcomes, thereby overriding learned stimulus-response associations. Here we examined in the slips-of-action task whether learnt habits can be changed using a planning technique - so-called implementation intentions - whereby people instruct themselves to enact a certain behaviour (or not) in the presence of a specific critical stimulus. Such simple 'if-then' instructions have previously been shown to support behavioural change in real-life settings, possibly because people verbally create new stimulus-response associations. Across four experiments we manipulated the intrinsic value of the stimuli and outcomes in the slips-of-action task: abstract stimuli and outcomes (Experiment 1), snack food stimuli and outcomes (Experiment 2), or a combination of both types (Experiment 3-4). Implementation intentions improved the ability to suppress previously learnt responses towards no-longer-valuable abstract outcomes (Experiment 1 and 3). However, when snacks were used as outcomes (Experiment 2 and 4) no beneficial effect of implementation intentions versus goal intentions was observed. The slips-of-action task is thus sensitive to planning techniques under certain circumstances. Yet, the absence of effects when using snacks as outcomes implies the possible importance of its hedonic outcome value for implementation intentions' effectiveness, which warrants further investigation.

Outcome-response (O-R) priming is at the core of various associative theories of human intentional action. This is a simple and parsimonious mechanism by which activation of outcome representations (e.g. thinking about the light coming on) leads to activation of the associated motor patterns required to achieve it (e.g. pushing the light switch). In the current manuscript, we review the evidence for such O-R associative links demonstrated by converging (yet until now, separate) strands of research. While there is a wealth of evidence that both the perceptual and motivational properties of an outcome can be encoded in the O-R association and mediate O-R priming, we critically examine the integration of these mechanisms and the conditions under which motivational factors constrain the sensory O-R priming effect. We discuss the clinical relevance of this O-R priming mechanism, whether it can satisfactorily account for human goal-directed behaviour, and the implications for theories of human action control.

Do people differ in their propensity to form habits? The current study related individual differences in habitual performance on the slips-of-action task to habit formation in real life. To this end, we developed a novel key-cover procedure that controls for the amount of repetition and motivation within a naturalistic setting. Participants received a key cover for the key to their home, which after several weeks was switched with a key cover that was previously attached to a dummy key. Participants recorded effort, time, attention, and mistakes in the key-selection process. Results were in line with established properties of habits, as attention decreased in the learning phase, yet effort, time, and mistakes increased after the key-cover switch. Performance on the slips-of-action task correlated negatively with changes in attention in the real-life key-cover task. This negative correlation may reflect that flexible behavioral adjustment requires more attention in people with a relatively weak goal-directed system. Electronic supplementary material The online version of this article (10.3758/s13420-018-0313-6) contains supplementary material, which is available to authorized users.