Selective cancellation of reactive or anticipated movements: Differences in speed of action reprogramming, but not stopping.

The ability to inhibit movements is an essential component of a healthy executive control system. Two distinct but commonly used tasks to assess motor inhibition are the stop signal task (SST) and the anticipated response inhibition (ARI) task. The SST and ARI tasks are similar in that they both require cancelation of a prepotent movement; however, the SST involves cancelation of a speeded reaction to a temporally unpredictable signal, while the ARI task involves cancelation of an anticipated response that the participant has prepared to enact at a wholly predictable time. 33 participants (mean age = 33.3 years, range = 18-55 years) completed variants of the SST and ARI task. In each task, the majority of trials required bimanual button presses, while on a subset of trials a stop signal indicated that one of the presses should be cancelled (i.e., motor selective inhibition). Additional variants of the tasks also included trials featuring signals which were to be ignored, allowing for insights into the attentional component of the inhibitory response. Electromyographic (EMG) recordings allowed detailed comparison of the characteristics of voluntary action and cancellation. The speed of the inhibitory process was not influenced by whether the enacted movement was reactive (SST) or anticipated (ARI task). However, the ongoing (non-cancelled) component of anticipated movements was more efficient than reactive movements, as a result of faster action reprogramming (i.e., faster ongoing actions following successful motor selective inhibition). Older age was associated with both slower inhibition and slower action reprogramming across all reactive and anticipated tasks.

Stopping Speed in Response to Auditory and Visual Stop Signals Depends on Go Signal Modality.

Past research has found that the speed of the action cancellation process is influenced by the sensory modality of the environmental change that triggers it. However, the effect on selective stopping processes (where participants must cancel only one component of a multicomponent movement) remains unknown, despite these complex movements often being required as we navigate our busy modern world. Thirty healthy adults (mean age = 31.1 years, SD = 10.5) completed five response-selective stop signal tasks featuring different combinations of "go signal" modality (the environmental change baring an imperative to initiate movement; auditory or visual) and "stop signal" modality (the environmental change indicating that action cancellation is required: auditory, visual, or audiovisual). EMG recordings of effector muscles allowed detailed comparison of the characteristics of voluntary action and cancellation between tasks. Behavioral and physiological measures of stopping speed demonstrated that the modality of the go signal influenced how quickly participants cancelled movement in response to the stop signal: Stopping was faster in two cross-modal experimental conditions (auditory go - visual stop; visual go - auditory stop), than in two conditions using the same modality for both signals. A separate condition testing for multisensory facilitation revealed that stopping was fastest when the stop signal consisted of a combined audiovisual stimulus, compared with all other go-stop stimulus combinations. These findings provide novel evidence regarding the role of attentional networks in action cancellation and suggest modality-specific cognitive resources influence the latency of the stopping process.

Modeling key intermediates during anaerobic digestion of lipid rich kitchen waste with an extended ADM1.

Quantitative dynamics of the key intermediates, gases and carbohydrates during anaerobic digestion of different lipid rich kitchen waste and lipid rich model kitchen waste were modeled. Six batch reactors loaded with 25 g VS  l - 1 ( ∼ 39  g O 2  l - 1 ) kitchen waste and model kitchen waste during a batch experiment were considered in simulation. Observed dynamics of carbohydrates, volatile organic acids and gases were described by an extended benchmark simulation model no. 2 (BSM2). In this study the extended BSM2 included a more detailed ß -oxidation for prediction of caproic acid. Furthermore, the extensions included carbohydrate digestion with an additional intermediate before propionic acid was released. In addition, a novel simplification approach for initial pH estimation was successfully applied. For parameter estimation a Markov Chain Monte Carlo method was used to obtain parameter distributions. With the presented model it was possible even with no calibrated data to predict point of times of intermediates maxima and propionic acid with relative stable concentration over several days for kitchen waste.

Working memory signals in early visual cortex are present in weak and strong imagers.

It has been suggested that visual images are memorized across brief periods of time by vividly imagining them as if they were still there. In line with this, the contents of both working memory and visual imagery are known to be encoded already in early visual cortex. If these signals in early visual areas were indeed to reflect a combined imagery and memory code, one would predict them to be weaker for individuals with reduced visual imagery vividness. Here, we systematically investigated this question in two groups of participants. Strong and weak imagers were asked to remember images across brief delay periods. We were able to reliably reconstruct the memorized stimuli from early visual cortex during the delay. Importantly, in contrast to the prediction, the quality of reconstruction was equally accurate for both strong and weak imagers. The decodable information also closely reflected behavioral precision in both groups, suggesting it could contribute to behavioral performance, even in the extreme case of completely aphantasic individuals. Our data thus suggest that working memory signals in early visual cortex can be present even in the (near) absence of phenomenal imagery.

Nonfrontal Control of Working Memory.

Items held in visual working memory can be quickly updated, replaced, removed, and even manipulated in accordance with current behavioral goals. Here, we use multivariate pattern analyses to identify the patterns of neuronal activity that realize the executive control processes supervising these flexible stores. We find that portions of the middle temporal gyrus and the intraparietal sulcus represent what item is cued for continued memorization independently of representations of the item itself. Importantly, this selection-specific activity could not be explained by sensory representations of the cue and is only present when control is exerted. Our results suggest that the selection of memorized items might be controlled in a distributed and decentralized fashion. This evidence provides an alternative perspective to the notion of "domain general" central executive control over memory function.

Impaired motor inhibition during perceptual inhibition in older, but not younger adults: a psychophysiological study.

The prefrontal cortex (PFC) governs the ability to rapidly cancel planned movements when no longer appropriate (motor inhibition) and ignore distracting stimuli (perceptual inhibition). It is unclear to what extent these processes interact, and how they are impacted by age. The interplay between perceptual and motor inhibition was investigated using a Flanker Task, a Stop Signal Task and a combined Stop Signal Flanker Task in healthy young (n = 33, Mean = 24 years) and older adults (n = 32, Mean = 71 years). PFC activity was measured with functional near-infrared spectroscopy (fNIRS), while electromyography (EMG) measured muscle activity in the fingers used to respond to the visual cues. Perceptual inhibition (the degree to which incongruent flankers slowed response time to a central cue) and motor inhibition (the speed of cancellation of EMG activation following stop cues) independently declined with age. When both processes were engaged together, PFC activity increased for both age groups, however only older adults exhibited slower motor inhibition. The results indicate that cortical upregulation was sufficient to compensate for the increased task demands in younger but not older adults, suggesting potential resource sharing and neural limitations particularly in older adults.

Dissociating attentional capture from action cancellation during the inhibition of bimanual movement.

Inhibiting ongoing responses when environmental demands change is a critical component of motor control. Experimentally, the stop signal task (SST) represents the gold standard response inhibition paradigm. However, an emerging body of evidence suggests that the SST conflates two dissociable sources of inhibition, namely an involuntarily pause associated with attentional capture and the (subsequent) voluntary cancellation of action. The extent to which these processes also occur in other response tasks is unknown. Younger n = 24 (20-35 years) and older n = 23 (60-85 years) adults completed tasks involving rapid unimanual or bimanual responses to visual stimuli. A subset of trials required cancellation of one component of an initial bimanual response (i.e., selective stop task; stop left response, continue right response) or enacting an additional response (e.g., press left button as well as right button). Critically, both tasks involved some infrequent stimuli baring no behavioral imperative (i.e., they had to be ignored). EMG recordings of voluntary responses during stopping tasks revealed bimanual covert responses (muscle activation, which was suppressed before a button press ensued), consistent with a pause process, following both stop and ignore stimuli, before the required response was subsequently enacted. Critically, we also observed the behavioral consequences of a similar involuntary pause in trials where action cancellation was not part of the response set. Notably, the period over which movements were susceptible to response delays from additional stimuli was longer for older adults than younger adults. The findings demonstrate that an involuntary attentional component of inhibition significantly contributes to action cancellation processes.

Diverse PSMA expression in primary prostate cancer: reason for negative [68Ga]Ga-PSMA PET/CT scans? Immunohistochemical validation in 40 surgical specimens.

PURPOSE: The purpose of this study was to immunohistochemically validate the primary tumor PSMA expression in prostate cancer (PCa) patients imaged with [68Ga]Ga-PSMA PET/CT prior to surgery, with special consideration of PET-negative cases. METHODS: The study included 40 men with newly diagnosed treatment-naïve PCa imaged with [68Ga]Ga-PSMA I&T PET/CT as part of the diagnostic work-up prior to radical prostatectomy. All primary tumors were routinely stained with H&E. In addition, immunohistochemical staining of PSMA was performed and the immunoreactive score (IRS) was computed as semiquantitative measure. Subsequently, imaging findings were correlated to histopathologic results. RESULTS: Eighty-three percent (33/40) of patients presented focal uptake of [68Ga]Ga-PSMA I&T in the primary tumor in at least one prostate lobe. Among PSMA-PET positive patients, one-third had lymph node metastases (LNM) detected by post-operative histopathology, while in PET negative patients, only 1 out of 7 presented with regional LN involvement; PSMA-avid distant lesions, predominantly in bones, were observed in 15% and 0% of patients, respectively. The median IRS classification of PSMA expression in tumor tissue was 2 (range, 1-3) both in PSMA-PET positive and negative prostate lobes, with significantly different interquartile range: 2-3 vs. 2-2, respectively (p = 0.03). The median volume of PSMA-PET positive tumors was 5.4 mL (0.2-32.9) as compared to 1.6 mL (0.3-18.3) of PET-negative tumors (p < 0.001). There was a significant but weak correlation between SUVmax and percentage of PSMA-positive tumor cells (r = 0.46, p < 0.001). A total of 35/44 (~80%) lobes were positive in PSMA-PET imaging, when a cut-off percentage of PSMA-positive cells was ≥ 90%, while 19/36 (~53%) lobes with < 90% PSMA-positive cells were PSMA-PET negative. CONCLUSION: Positive [68Ga]Ga-PSMA I&T PET/CT scan of primary tumor of PCa results from a combination of factors, such as homogeneity and intensity of PSMA expression, tumor volume and grade, with a cutoff value of ≥ 90% PSMA-positive cells strongly determining PET-positivity. Focal accumulation of [68Ga]Ga-PSMA in the primary tumor may correlate positively with aggressiveness of prostate cancer, harboring higher risk of regional LN involvement and distant metastatic spread.

Modeling grid fields instead of modeling grid cells : An effective model at the macroscopic level and its relationship with the underlying microscopic neural system.

A neuron's firing correlates are defined as the features of the external world to which its activity is correlated. In many parts of the brain, neurons have quite simple such firing correlates. A striking example are grid cells in the rodent medial entorhinal cortex: their activity correlates with the animal's position in space, defining 'grid fields' arranged with a remarkable periodicity. Here, we show that the organization and evolution of grid fields relate very simply to physical space. To do so, we use an effective model and consider grid fields as point objects (particles) moving around in space under the influence of forces. We reproduce several observations on the geometry of grid patterns. This particle-like behavior is particularly salient in a recent experiment in which two separate grid patterns merge. We discuss pattern formation in the light of known results from physics of two-dimensional colloidal systems. Notably, we study the limitations of the widely used 'gridness score' and show how physics of 2d systems could be a source of inspiration, both for data analysis and computational modeling. Finally, we draw the relationship between our 'macroscopic' model for grid fields and existing 'microscopic' models of grid cell activity and discuss how a description at the level of grid fields allows to put constraints on the underlying grid cell network.

A local measure of symmetry and orientation for individual spikes of grid cells.

Grid cells have attracted broad attention because of their highly symmetric hexagonal firing patterns. Recently, research has shifted its focus from the global symmetry of grid cell activity to local distortions both in space and time, such as drifts in orientation, local defects of the hexagonal symmetry, and the decay and reappearance of grid patterns after changes in lighting condition. Here, we introduce a method that allows to visualize and quantify such local distortions, by assigning both a local grid score and a local orientation to each individual spike of a neuronal recording. The score is inspired by a standard measure from crystallography, which has been introduced to quantify local order in crystals. By averaging over spikes recorded within arbitrary regions or time periods, we can quantify local variations in symmetry and orientation of firing patterns in both space and time.

Adoption Patterns of Bronchoscopic Lung Volume Reduction Procedures in Germany and Predicted Procedure Volumes for Other European Countries.

BACKGROUND: Bronchoscopic lung volume reduction (BLVR) using valves and coils has been approved for use since 2003 and 2010, respectively. OBJECTIVE(S): To study adoption patterns of BLVR in an early-adopting country, and to estimate potential treatment volumes in other European countries. METHODS: Therapy- and age-specific volumes for endobronchial valve and coil procedures were obtained from German federal statistics for 2007-2016. Therapy-specific and total BLVR procedure volumes and growth were computed, and patterns in treatment age and device utilization analyzed. Patient volumes for other European countries were predicted using mean German patient volumes of the last 3 data years and age-specific population and emphysema incidences. RESULTS: Over the study period, annual BLVR procedure volumes grew from 91 to 2,053 (+2,256%), reaching a peak of 2,556 procedures in 2013. Coil procedures constituted 36% of the total volume in 2016. Treatment age was stable over time, with highest procedure counts in age group 60-64 years for valves and 65-69 years for coils. A limited increase in device use per procedure was observed. For -Germany, 1,655 newly treated BLVR patients were estimated per year, approximating about 5% of the annual newly diagnosed severe emphysema cases. Predicted volume estimates for other European countries ranged from 1 for Liechtenstein to 1,226 for France. CONCLUSIONS: Analysis of -German procedure data show pronounced BLVR therapy uptake in the early years of adoption, with the more recently introduced coil therapy used in about one-third of patients. Estimated patient volumes to date constitute only a small fraction of the severe emphysema population.

Insights from eight years of adoption experience of transcatheter mitral valve repair in Germany: observed utilisation patterns and impact on overall mitral valve procedure volumes.

AIMS: The German healthcare system was among the first to introduce transcatheter mitral valve repair (TMVR) into routine care. The objective of this study was to analyse adoption and utilisation patterns and to estimate the impact of TMVR availability on mitral valve (MV) procedure volumes in the first eight years after commercialisation. METHODS AND RESULTS: Procedure volumes were collected from German Federal Statistics Office databases for TMVR and mitral valve surgery (MVS) from 2008-2015. Procedure volumes were stratified by age group (<65, 65-74, 75-84, ≥85 years). Overall procedure volumes grew from 14,525 to 24,898 (+71%). MVS procedures grew from 14,477 to 20,402 (+41%) (p=0.008). The proportion of TMVR procedures grew from 0.3% (48 procedures) to 18.1% (4,496 procedures) (p=0.008). In 2015, TMVR use reached 5%, 15%, 31%, and 68% of overall MV procedures in the studied age groups (<65, 65-74, 75-84, ≥85 years). MVS volumes grew in all age groups, with the highest increase in the age group <65 (+2,945). CONCLUSIONS: The availability of TMVR has contributed to a pronounced increase in MV procedure volumes in Germany. Simultaneously, MVS procedure volumes continued to grow substantially. The highest increase of TMVR was observed in elderly populations, suggesting referral of patients with MV disease previously left untreated.

Changes in medication cost observed in chronic cluster headache patients treated with sphenopalatine ganglion (SPG) stimulation: Analysis based on 1-year data from the Pathway R-1 Registry.

Background On-demand stimulation of the sphenopalatine ganglion (SPG) by means of an implantable neurostimulation system has been shown to be a safe and effective therapy for treatment-refractory cluster headache patients. Our objective was to estimate changes in cluster headache medication cost observed in SPG-treated chronic patients. Methods Detailed patient-level data of 71 chronic patients treated with the Pulsante® SPG Microstimulator System were available from the Pathway R-1 Registry through 12 months' follow-up. We used utilization data of preventive and acute medications reported at baseline, 3, 6, 9, and 12 months to estimate annualized drug costs for SPG-treated patients and compared it to baseline. Cost estimates for all drug/dosage combinations were developed based on German medication prices for 2016. Results In the base case analysis, mean annual acute and preventive medication costs decreased from €14,178 to €6924 (-€7254; -51%), and €559 to €328 (-€231; -41%), respectively, leading to total estimated annual drug cost savings of €7484, 97% of which were attributable to acute medications. Conclusions Our analysis suggests that SPG stimulation for the treatment of chronic cluster headache is associated with pronounced reductions in cluster headache medication usage that might lead to sizable annual savings in medication costs.

Learning place cells, grid cells and invariances with excitatory and inhibitory plasticity.

Neurons in the hippocampus and adjacent brain areas show a large diversity in their tuning to location and head direction, and the underlying circuit mechanisms are not yet resolved. In particular, it is unclear why certain cell types are selective to one spatial variable, but invariant to another. For example, place cells are typically invariant to head direction. We propose that all observed spatial tuning patterns - in both their selectivity and their invariance - arise from the same mechanism: Excitatory and inhibitory synaptic plasticity driven by the spatial tuning statistics of synaptic inputs. Using simulations and a mathematical analysis, we show that combined excitatory and inhibitory plasticity can lead to localized, grid-like or invariant activity. Combinations of different input statistics along different spatial dimensions reproduce all major spatial tuning patterns observed in rodents. Our proposed model is robust to changes in parameters, develops patterns on behavioral timescales and makes distinctive experimental predictions.

Binary Mixtures of Particles with Different Diffusivities Demix.

The influence of size differences, shape, mass, and persistent motion on phase separation in binary mixtures has been intensively studied. Here we focus on the exclusive role of diffusivity differences in binary mixtures of equal-sized particles. We find an effective attraction between the less diffusive particles, which are essentially caged in the surrounding species with the higher diffusion constant. This effect leads to phase separation for systems above a critical size: A single close-packed cluster made up of the less diffusive species emerges. Experiments for testing our predictions are outlined.

In-hospital outcomes and long-term mortality according to sex and management strategy in acute myocardial infarction. Insights from the French ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2005 Registry.

BACKGROUND: The early mortality of acute myocardial infarction (AMI) has dramatically decreased in the recent past. Whether the previously reported sex disparities in use of invasive strategies (IS) persist and translate into differences in outcomes deserves to be examined. METHODS: We used the data from a nationwide French prospective multicentre registry from 3,670 AMI patients (1155 women (31.5%), 2515 men (68.5%)) recruited in 223 centres in 2005 and followed-up for 5 years. We examined in-hospital outcomes and 5-year mortality in patients categorized according to sex and use of IS (i.e. coronary angiography during the hospitalisation with a view to revascularisation). RESULTS: IS was less frequently used in women than in men (adjusted OR=0.66; 95% CI: 0.52-0.85), regardless of the type of AMI, age group or risk category, while use of recommended medications was similar at 48 hours and discharge. In-hospital mortality did not differ according to sex, whatever the age group and use of an IS. At 5 years, overall and post-discharge mortality were similar in men and women. However, IS was associated with lower 5-year mortality in women (HR=0.66; 95% CI: 0.51-0.86) as in men (HR=0.48; 95% CI: 0.38-0.60) and there was no sex-strategy interaction. CONCLUSIONS: Invasive strategy remains less frequently used in women than in men, yet is associated with improved five-year survival irrespective of sex. Whether reducing the sex gap in its use would translate into a higher survival in women remains an open question. CLINICAL TRIAL REGISTRATION: NCT 00673036.

[How to diagnose an acute coronary syndrome in 2015?]. / Comment diagnostiquer un syndrome coronaire aigu en 2015 ?

Acute coronary syndromes (ACS) are characterized by sudden, reduced blood flow to the heart leading to myocardial ischemia, caused by atherosclerotic plaque rupture or erosion, with differing degrees of superimposed thrombosis. The most frequent clinical presentation is intermittent chest pain secondary to coronary artery subocclusion. The absence of electrocardiogram (ECG) abnormalities in a high proportion of patients after pain relief renders the diagnosis difficult. Clinical evaluation is of great importance to distinguish patients with ACS within the very large proportion with chest pain. Troponins play a central role in establishing the diagnosis, however false positive tests are frequent in patients with a low pretest probability and may lead to unnecessary invasive cardiac testing. Prolonged anginal pains of more than 10 minutes are generally secondary to epicardial coronary artery occlusion and associated with ECG abnormalities in a large majority of patients. Patients with persistent ST-elevation should be immediately transported to the hospital for emergent early reperfusion therapy, which reduces myocardial injury and is associated with major improvement of prognosis.

Evolution of mitral valve procedural volumes in the advent of endovascular treatment options: Experience at an early-adopting center in Germany.

OBJECTIVES: Our objectives were to assess the evolution of surgical and endovascular mitral valve procedural volumes and to study utilization and reimbursement effects of transcatheter mitral valve repair (TMVR) at our center and to put these in perspective with the corresponding data at the national level. BACKGROUND: TMVR using the MitraClip system has been available in Germany since 2008 as a complementary treatment option for high-risk or inoperable patients. METHODS: Relevant procedure codes were identified for 2006-2012 and yearly utilization volumes obtained from our center's databases and from the national statistics office. Volumes were analyzed in total, and stratified by treatment approach. Procedure reimbursement at our center was determined for years 2007-2012. RESULTS: At our center, 378 MitraClip procedures were performed from 2008 to 2012. During this period, surgical volumes grew at an average of 10.6% annually (2008: 262; 2012: 392; 49.6% total growth rate). Total surgical and TMVR reimbursement increased from EUR 3.8 million (2007) to EUR 7.9 million (2012). By comparison, mitral valve procedural volumes grew by 56.1% from 2006 to 2012 at the national level, with TMVR constituting 9.1% of 20,328 procedures in 2012. Since the introduction of MitraClip, nationwide surgical procedural volumes grew at an average of 6.3% annually (2008: 14,477; 2012: 18,478; 27.6% total growth rate). CONCLUSIONS: Growth in procedural volumes during 2006-2012 reflects an increasing supply and subsequent demand for mitral valve procedures. The introduction of TMVR has contributed to overall growth, and has not reduced continued growth in surgical volumes. Our center-specific analysis suggests a "halo effect" of an integrated approach to mitral valve disease contributing to additional growth in surgical and overall reimbursement volumes.

Continuous treatment with antidementia drugs in Germany 2003-2013: a retrospective database analysis.

BACKGROUND: Continuous treatment is an important indicator of medication adherence in dementia. However, long-term studies in larger clinical settings are lacking, and little is known about moderating effects of patient and service characteristics. METHODS: Data from 12,910 outpatients with dementia (mean age 79.2 years; SD = 7.6 years) treated between January 2003 and December 2013 in Germany were included. Continuous treatment was analysed using Kaplan-Meier curves and log-rank tests. In addition, multivariate Cox regression models were fitted with continuous treatment as dependent variable and the predictors antidementia agent, age, gender, medical comorbidities, physician specialty, and health insurance status. RESULTS: After one year of follow-up, nearly 60% of patients continued drug treatment. Donezepil (HR: 0.88; 95% CI: 0.82-0.95) and memantine (HR: 0.85; 0.79-0.91) patients were less likely to be discontinued treatment as compared to rivastigmine users. Patients were less likely to be discontinued if they were treated by specialist physicians as compared to general practitioners (HR: 0.44; 0.41-0.48). Younger male patients and patients who had private health insurance had a lower discontinuation risk. Regarding comorbidity, patients were more likely to be continuously treated with the index substance if a diagnosis of heart failure or hypertension had been diagnosed at baseline. CONCLUSIONS: Our results imply that besides type of antidementia agent, involvement of a specialist in the complex process of prescribing antidementia drugs can provide meaningful benefits to patients, in terms of more disease-specific and continuous treatment.

Interpreting a pumping test influenced by another well in an anisotropic aquifer.

In confined aquifers the influence of neighboring active wells is often neglected when interpreting a pumping test. This can, however, lead to an erroneous interpretation of the pumping test data. This article presents simple methods to evaluate the transmissivity tensor and storativity of an anisotropic confined aquifer when there is an interfering well in the neighborhood of the tested well. Two methods have been developed depending on whether the tested well or the interfering well is the first in operation. These new methods yield better estimates of the hydraulic parameters than when the influence of the interfering well is neglected. These methods have then been used on data obtained from numerical models with an interfering well and the results have been compared to an analytical method that neglects the influence of the interfering well. The methods require knowledge of the pumping rate of the interfering well and the time elapsed since the pumping started in each well. If the interfering well started pumping before the tested well, the method does not require knowledge of the aquifer piezometric level at the beginning of the test, which is often unknown in this case. As for the method without interference, at least three monitoring wells (MWs) are needed, the position of which influences the accuracy of the estimated parameters. Some recommendations concerning MWs position have been given to get more accurate results according to the sought parameter.