Increased fronto-striatal reward prediction errors moderate decision making in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) has been linked to functional abnormalities in fronto-striatal networks as well as impairments in decision making and learning. Little is known about the neurocognitive mechanisms causing these decision-making and learning deficits in OCD, and how they relate to dysfunction in fronto-striatal networks. METHOD: We investigated neural mechanisms of decision making in OCD patients, including early and late onset of disorder, in terms of reward prediction errors (RPEs) using functional magnetic resonance imaging. RPEs index a mismatch between expected and received outcomes, encoded by the dopaminergic system, and are known to drive learning and decision making in humans and animals. We used reinforcement learning models and RPE signals to infer the learning mechanisms and to compare behavioural parameters and neural RPE responses of the OCD patients with those of healthy matched controls. RESULTS: Patients with OCD showed significantly increased RPE responses in the anterior cingulate cortex (ACC) and the putamen compared with controls. OCD patients also had a significantly lower perseveration parameter than controls. CONCLUSIONS: Enhanced RPE signals in the ACC and putamen extend previous findings of fronto-striatal deficits in OCD. These abnormally strong RPEs suggest a hyper-responsive learning network in patients with OCD, which might explain their indecisiveness and intolerance of uncertainty.

Improvement in imaging common temporal bone pathologies at 3 T MRI: small structures benefit from a small field of view.

AIM: To compare image quality and evaluate its clinical importance in common temporal bone pathologies of a pTX-SPACE (parallel transmit [pTX] three-dimensional turbo spin-echo with variable flip angle [SPACE]) magnetic resonance imaging (MRI) sequence improved for spatial resolution to a standard-SPACE sequence exhibiting the same scan time at 3 T. MATERIALS AND METHODS: Thirty-four patients were examined using a standard-SPACE and resolution improved pTX-SPACE sequence at 3 T MRI. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and image quality were assessed. Diseases investigated were vestibular schwannoma (VS), intralabyrinthine schwannoma (ILS), inner ear malformations, labyrinthitis, temporal bone fractures, and situation after VS resection. RESULTS: Edge definition, intratumoural pattern, discrimination of VS from the modiolus and edge definition of ILS, separability from the spiral lamina, and detectability within cochlear turns were improved on the pTX-SPACE sequence. Detectability of malformations, post-traumatic changes, and discrimination of the cochlear and facial nerve after VS resection was improved on the pTX-SPACE sequence. In labyrinthitis, pTX-SPACE was not superior to standard-SPACE. The SNR and CNR were significantly reduced for pTX-SPACE. CONCLUSIONS: pTX-SPACE significantly improves the detectability of temporal bone diseases, in particular, VS, ILS, and post-VS resection.

EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis.

In this article, the 2009 European League Against Rheumatism (EULAR) recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated. The 2009 recommendations were on the management of primary small and medium vessel vasculitis. The 2015 update has been developed by an international task force representing EULAR, the European Renal Association and the European Vasculitis Society (EUVAS). The recommendations are based upon evidence from systematic literature reviews, as well as expert opinion where appropriate. The evidence presented was discussed and summarised by the experts in the course of a consensus-finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) determined. In addition to the voting by the task force members, the relevance of the recommendations was assessed by an online voting survey among members of EUVAS. Fifteen recommendations were developed, covering general aspects, such as attaining remission and the need for shared decision making between clinicians and patients. More specific items relate to starting immunosuppressive therapy in combination with glucocorticoids to induce remission, followed by a period of remission maintenance; for remission induction in life-threatening or organ-threatening AAV, cyclophosphamide and rituximab are considered to have similar efficacy; plasma exchange which is recommended, where licensed, in the setting of rapidly progressive renal failure or severe diffuse pulmonary haemorrhage. These recommendations are intended for use by healthcare professionals, doctors in specialist training, medical students, pharmaceutical industries and drug regulatory organisations.

The Swiss National Registry for Primary Immunodeficiencies: report on the first 6 years' activity from 2008 to 2014.

The Swiss National Registry for Primary Immunodeficiency Disorders (PID) was established in 2008, constituting a nationwide network of paediatric and adult departments involved in the care of patients with PID at university medical centres, affiliated teaching hospitals and medical institutions. The registry collects anonymized clinical and genetic information on PID patients and is set up within the framework of the European database for PID, run by the European Society of Immunodeficiency Diseases. To date, a total of 348 patients are registered in Switzerland, indicating an estimated minimal prevalence of 4·2 patients per 100 000 inhabitants. Distribution of different PID categories, age and gender are similar to the European cohort of currently 19 091 registered patients: 'predominantly antibody disorders' are the most common diseases observed (n = 217/348, 62%), followed by 'phagocytic disorders' (n = 31/348, 9%). As expected, 'predominantly antibody disorders' are more prevalent in adults than in children (78 versus 31%). Within this category, 'common variable immunodeficiency disorder' (CVID) is the most prevalent PID (n = 98/217, 45%), followed by 'other hypogammaglobulinaemias' (i.e. a group of non-classified hypogammaglobulinaemias) (n = 54/217, 25%). Among 'phagocytic disorders', 'chronic granulomatous disease' is the most prevalent PID (n = 27/31, 87%). The diagnostic delay between onset of symptoms and diagnosis is high, with a median of 6 years for CVID and more than 3 years for 'other hypogammaglobulinaemias'.

Reliability of the calculated maximal lactate steady state in amateur cyclists.

Complex performance diagnostics in sports medicine should contain maximal aerobic and maximal anaerobic performance. The requirements on appropriate stress protocols are high. To validate a test protocol quality criteria like objectivity and reliability are necessary. Therefore, the present study was performed in intention to analyze the reliability of maximal lactate production rate ([Formula: see text]Lamax) by using a sprint test, maximum oxygen consumption ([Formula: see text]O2max) by using a ramp test and, based on these data, resulting power in calculated maximum lactate-steady-state (PMLSS) especially for amateur cyclists. All subjects (n = 23, age 26 ± 4 years) were leisure cyclists. At three different days they completed first a sprint test to approximate [Formula: see text]Lamax. After 60 min of recreation time a ramp test to assess [Formula: see text]O2max was performed. The results of [Formula: see text]Lamax-test and [Formula: see text]O2max-test and the body weight were used to calculate PMLSS for all subjects. The intra class correlation (ICC) for [Formula: see text]Lamax and [Formula: see text]O2max was 0.904 and 0.987, respectively, coefficient of variation (CV) was 6.3% and 2.1%, respectively. Between the measurements the reliable change index of 0.11 mmol·l (-1)s (-1) for [Formula: see text]Lamax and 3.3 mlkg (-1)min (-1) for [Formula: see text]O2max achieved significance. The mean of the calculated PMLSS was 237 ± 72 W with an RCI of 9 W and reached with ICC = 0.985 a very high reliability. Both metabolic performance tests and the calculated PMLSS are reliable for leisure cyclists.

Comparison of selected lactate threshold parameters with maximal lactate steady state in cycling.

The aim of the present investigation was to compare power at "onset of blood lactate accumulation" (OBLA), "individual anaerobic threshold" (IAT) and "+1.5 mmol ∙ l(-1) lactate model" with power in maximal lactate steady state (MLSS) in cycling. However, there is a lack of studies concerning the absolute individual differences between different lactate parameters and MLSS.A total of 57 male participants performed several 30-min constant-load tests to determine MLSS by measuring blood lactate concentration (BLC). Depending on BLC, power was increased or decreased by 10 W in the following 30-min test. For detecting power at different threshold parameters, an incremental test was performed that began at 40 W and increased by 40 W every 4 min.Highly significant correlations were found between OBLA and MLSS: r=0.89 (mean difference -7.4 W); IAT and MLSS: r=0.83 (mean difference 12.4W), "+1.5 mmol ∙ l(-1) lactate model" and MLSS: r=0.88 (mean difference -37.4W). On average, the parameters of OBLA and IAT approximate MLSS with no significant differences. The "+1.5 mmol ∙ l(-1) lactate model" underestimates MLSS significantly.Based on Bland-and-Altman, the comparison of power of all threshold parameters with power in MLSS shows great individual differences despite the high regression coefficients and low mean differences between these methods.

Reliability of maximal lactate-steady-state.

The aim of this study was the analysis of reliability and day-to-day-variability of power (PMLSS), blood lactate concentration (BLCMLSS) and heart rate (HRMLSS) in maximal lactate- steady-state during cycle ergometry. 32 male subjects (25±3 years, 180±7 cm, 76±8 kg) have undergone several constant-load-tests lasting 30 min to determine 4 PMLSS. During the test, blood-samples were taken from the earlobe after 4, 8,10, 14, 18, 22, 26 und 30 min for detecting the BLCMLSS. PMLSS was defined as the highest workload that can be maintained without accumulation of BLC by more than 0.05 mmol/l/min during the last 20 min. Mean PMLSS was 244±45 W, according to 75% of VO2max. Mean of BLCMLSS was 5.3±1.5 mmol/l/min, mean of HRMLSS was 166±10 1/min. The coefficient of variability (CV) was calculated for PMLSS, BLCMLSS and HRMLSS with 3%, 16.6% and 6.3%, respectively. The Intra-Class-Coefficient for PMLSS, BLCMLSS and for HRMLSS was determined with 0.98 (p≤0.001), 0.71 (p≤0.001), 0.92 (p≤0.001) respectively. PMLSS and HRMLSS are characterized by a low day-to-day variability that is comparable with results of different lactate threshold concepts. In comparison to PMLSS, BLCMLSS shows a greater day-to-day-variability.

Neurocognitive basis of model-based decision making and its metacontrol in childhood.

Human behavior is supported by both goal-directed (model-based) and habitual (model-free) decision-making, each differing in its flexibility, accuracy, and computational cost. The arbitration between habitual and goal-directed systems is thought to be regulated by a process known as metacontrol. However, how these systems emerge and develop remains poorly understood. Recently, we found that while children between 5 and 11 years displayed robust signatures of model-based decision-making, which increased during this developmental period, there were substantial individual differences in the display of metacontrol. Here, we inspect the neurocognitive basis of model-based decision-making and metacontrol in childhood and focus this investigation on executive functions, fluid reasoning, and brain structure. A total of 69 participants between the ages of 6-13 completed a two-step decision-making task and an extensive behavioral test battery. A subset of 44 participants also completed a structural magnetic resonance imaging scan. We find that individual differences in metacontrol are specifically associated with performance on an inhibition task and individual differences in thickness of dorsolateral prefrontal, temporal, and superior-parietal cortices. These brain regions likely reflect the involvement of cognitive processes crucial to metacontrol, such as cognitive control and contextual processing.

Deep learning-assisted radiomics facilitates multimodal prognostication for personalized treatment strategies in low-grade glioma.

Determining the optimal course of treatment for low grade glioma (LGG) patients is challenging and frequently reliant on subjective judgment and limited scientific evidence. Our objective was to develop a comprehensive deep learning assisted radiomics model for assessing not only overall survival in LGG, but also the likelihood of future malignancy and glioma growth velocity. Thus, we retrospectively included 349 LGG patients to develop a prediction model using clinical, anatomical, and preoperative MRI data. Before performing radiomics analysis, a U2-model for glioma segmentation was utilized to prevent bias, yielding a mean whole tumor Dice score of 0.837. Overall survival and time to malignancy were estimated using Cox proportional hazard models. In a postoperative model, we derived a C-index of 0.82 (CI 0.79-0.86) for the training cohort over 10 years and 0.74 (Cl 0.64-0.84) for the test cohort. Preoperative models showed a C-index of 0.77 (Cl 0.73-0.82) for training and 0.67 (Cl 0.57-0.80) test sets. Our findings suggest that we can reliably predict the survival of a heterogeneous population of glioma patients in both preoperative and postoperative scenarios. Further, we demonstrate the utility of radiomics in predicting biological tumor activity, such as the time to malignancy and the LGG growth rate.

Changes in AVM angio-architecture and hemodynamics after stereotactic radiosurgery assessed by dynamic MRA and phase contrast flow assessments: a prospective follow-up study.

OBJECTIVES: Assessment of changes in the hemodynamics of Arteriovenous malformations (AVM) induced by radiosurgery by MR Phase contrast (PC) measurements of the internal carotid arteries (ICA). METHODS: 65 patients shortly after or before stereotactic radiosurgery underwent MRI including morphological series, MR-Angiography (Time-of-flight, dynamic MRA) and bilateral ECG triggered MR phase contrast (PC) measurements of the ICA. Follow-up was performed in 34 patients. The observation period was up to 4 years. RESULTS: Over all subjects, a significant relationship between mean arterial blood flow in the ICA on the side of the lesion and AVM volume was revealed (p = 0,0002). In large (>10 ccm) and medium-sized AVMs, (>3, 5 ≤ 10 ccm) the blood flow was significantly increased on the side of the AVM (p = 0,0004; p = 0,047), whereas in lesions <3, 5 ccm, no significant rise of the mean blood flow was detectable. At follow-up, the mean blood flow in the ipsilateral artery was not increased anymore compared to the contralateral ICA (p = 0,11). These changes correlated with a significant reduction of the average AVM volume (p = 0, 0026). CONCLUSIONS: The AVM angioarchitecture has significant impact on the blood flow in feeding arteries. A significant reduction of the shunt volume by successful radiotherapy leads to normalization of the hemodynamics.

[Mild cognitive impairment: diagnostic value of different MR techniques]. / "Mild cognitive impairment": Diagnostische Wertigkeit verschiedener MR-Techniken.

In view of an increasingly aging population the prevalence of dementia is also expected to increase rapidly. As well as clinical, neuropsychological and laboratory procedures magnetic resonance imaging (MRI) plays an important role in the early diagnosis of dementia which is important in the precursor stage of mild cognitive impairment (MCI). On the one hand this stage is associated with an increased risk of dementia and on the other hand an early treatment in this stage could attenuate development of the disease. In addition to morphological changes different functional MRI techniques can help in the early diagnosis of dementia and the precursor stages. Moreover, it is important to detect those MCI patients who are at particularly risk for developing dementia. In the differentiation of converters to non-converters initial studies suggest that particularly voxel-based morphometry, MR spectroscopy and diffusion tensor imaging can provide important additional information.

On the Development of OCD.

OCD most often arises before adulthood with adolescence being a particularly vulnerable period. This is also a time when both brain and cognition undergo fundamental developmental change and reorganisation. However, the neurocognitive mechanisms that drive the emergence of OCD during development are still largely unknown. In this chapter, I review the relatively sparse literature on the developmental aspects of OCD and I discuss the symptomatic, cognitive and neural patterns in OCD and the developing mind. I highlight how we need to understand the emergence of cognitive impairments and neural alteration in a developmental context if we want to understand more about the mechanisms that give rise to OCD. Moreover, I outline how we best approach this challenge to overcome the current limitations in research.

The effect of spironolactone on diastolic function in haemodialysis patients.

Heart failure with preserved ejection fraction (HFpEF) is highly prevalent in patients on maintenance haemodialysis (HD) and lacks effective treatment. We investigated the effect of spironolactone on cardiac structure and function with a specific focus on diastolic function parameters. The MiREnDa trial examined the effect of 50 mg spironolactone once daily versus placebo on left ventricular mass index (LVMi) among 97 HD patients during 40 weeks of treatment. In this echocardiographic substudy, diastolic function was assessed using predefined structural and functional parameters including E/e'. Changes in the frequency of HFpEF were analysed using the comprehensive 'HFA-PEFF score'. Complete echocardiographic assessment was available in 65 individuals (59.5 ± 13.0 years, 21.5% female) with preserved left ventricular ejection fraction (LVEF > 50%). At baseline, mean E/e' was 15.2 ± 7.8 and 37 (56.9%) patients fulfilled the criteria of HFpEF according to the HFA-PEFF score. There was no significant difference in mean change of E/e' between the spironolactone group and the placebo group (+ 0.93 ± 5.39 vs. + 1.52 ± 5.94, p = 0.68) or in mean change of left atrial volume index (LAVi) (1.9 ± 12.3 ml/m2 vs. 1.7 ± 14.1 ml/m2, p = 0.89). Furthermore, spironolactone had no significant effect on mean change in LVMi (+ 0.8 ± 14.2 g/m2 vs. + 2.7 ± 15.9 g/m2; p = 0.72) or NT-proBNP (p = 0.96). Treatment with spironolactone did not alter HFA-PEFF score class compared with placebo (p = 0.63). Treatment with 50 mg of spironolactone for 40 weeks had no significant effect on diastolic function parameters in HD patients.The trial has been registered at clinicaltrials.gov (NCT01691053; first posted Sep. 24, 2012).

Genetic and sexual separation between insect resistant and susceptible Barbarea vulgaris plants in Denmark.

Co-evolution between herbivores and plants is believed to be one of the processes creating Earth's biodiversity. However, it is difficult to disentangle to what extent diversification is really driven by herbivores or by other historical-geographical processes like allopatric isolation. In the cruciferous plant Barbarea vulgaris, some Danish individuals are resistant to herbivory by flea beetles (Phyllotreta nemorum), whereas others are not. The flea beetles are, in parallel, either resistant or susceptible to the plants defenses. To understand the historical-evolutionary framework of these interactions, we tested how genetically divergent resistant and susceptible plants are, using microsatellite markers. To test whether they are reproductively fully compatible, resistant and susceptible plants were grown intermixed in an outdoor experiment, and the paternity of open-pollinated offspring was determined by analysis of molecular markers. Resistant and susceptible Danish plants were genetically strongly differentiated and produced significantly fewer hybrids than expected from random mating or nearest neighbour mating. Our results suggest that the two types belong to different evolutionary lineages that have been (partly) isolated at some time, during which genetic and reproductive divergence evolved. A parsimonious scenario could be that the two plant types were isolated in different refugia during the previous ice age, from which they migrated into and met in Denmark and possibly neighbouring regions. If so, resistance and susceptibility has for unknown reasons become associated with the different evolutionary lineages.

Genetic variation of inbreeding depression among floral and fitness traits in Silene nutans.

The magnitude and variation of inbreeding depression (ID) within populations is important for the evolution and maintenance of mixed mating systems. We studied ID and its genetic variation in a range of floral and fitness traits in a small and large population of the perennial herb Silene nutans, using controlled pollinations in a fully factorial North Carolina II design. Floral traits and early fitness traits, that is seed mass and germination rate, were not much affected by inbreeding (delta<0.2). In contrast, 'late' fitness traits and multiplicative fitness suffered severely from inbreeding (delta>0.4). Lack of genetic correlations indicated that ID in floral, early and late traits is genetically decoupled. There was a trend that the smaller population was less affected by ID than the large one, although the differences were not significant for most traits. Hence, evidence for purging of deleterious alleles remains inconclusive in this study. Genetic variation in ID among paternal families was statistically significant in most floral and all seed traits, but not in late fitness traits. However, some paternal families had delta<0.5, even in the multiplicative fitness measure that suffered most from ID (delta=0.74), suggesting that the mixed mating system of S. nutans might be evolutionary stable.

Long-term angiographic and histological results of a new hydrogel-containing filling coil in experimental rabbit aneurysms.

BACKGROUND: The aim of this study was to compare the performance of a new filling coil, the HydroFill device, to historical results of HydroSoft and bare platinum coil devices in experimental rabbit aneurysms. METHODS: Experimental aneurysms were constructed in rabbits and embolized with HydroFill (n=32), HydroSoft (n=48), or bare platinum coil (n=47) devices. Angiographic occlusion was evaluated post-treatment and at 1 month (n=55), 3 month (n=20), 6 month (n=35), and 12 month (n=12) follow-ups according to the Raymond scale. The aneurysms were analyzed histologically for neointima formation, thrombus organization, and inflammation. Continuous and discrete results were compared using ANOVA/t-test and chi (2) tests, respectively. RESULTS: Volumetric occlusion of the aneurysm sac was increased in the HydroFill group compared to the HydroSoft and platinum coil groups. Protrusions into the parent artery were common in all treatment groups due to the treatment of wide-necked aneurysms without the use of balloons or stents. Although angiographic occlusion post-treatment scores were reduced in the HydroFill group compared to the HydroSoft and platinum coil groups, stable/progressive occlusion was increased in the HydroFill group compared to the platinum coil group. Histologically, neointima formation and thrombus organization scores were increased in the HydroFill and HydroSoft groups compared to the platinum coil group at 3 months. Although there were some differences in the scoring, inflammation was generally minimal to mild in all three groups. CONCLUSION: The HydroFill device, with its high levels of volumetric filling, increased stable/progressive occlusion at follow-up, increased neointima formation, and increased thrombus organization, shows promise for clinical use.

[Significance of MR angiography for imaging diagnostics of carotid artery diseases]. / Stellenwert der MR-Angiographie zur bildgebenden Diagnostik von Erkrankungen der Karotiden.

During the last decade, magnetic resonance angiography (MRA) evolved to an essential method for radiological diagnostics of extracranial arteries' diseases. Contrast enhanced MRA enables meanwhile the acquisition of angiographic series in high diagnostic quality comparable to that originating from conventional DSA. Due to MRA, conventional DSA anymore plays a crucial role in the diagnostic assessment of carotid artery disease or highly vascularised tumors of the head and neck region. Besides reliable quantification of carotid stenoses, highly resolved MRI sequences provide a promising approach for characterization of plaque morphologies and thereby contribute to turn the risk for a stroke calculable. Furthermore, MRA has nearly replaced DSA in radiographics of carotid artery dissections whereas MRA has especially emerged as an appropriate method to visualize the intramural hematoma which is evidentiary for the diagnosis. However, not all methods of MRA are equivalent in respect to their diagnostic value. While CE MRA is able to completely substitute DSA in many clinical questions, applicability of flow-dependent Time-of-flight (TOF) or phase-contrast (PC) MRA is limited due to their distinct susceptibility to motion or flow-related artefacts.

[MR spectroscopy in dementia]. / MR-Spektroskopie bei Demenz.

With an increasingly aging population we are faced with the problem of an increasing number of dementia patients. In addition to clinical, neuropsychological and laboratory procedures, MRI plays an important role in the early diagnosis of dementia. In addition to various morphological changes functional changes can also help in the diagnosis and differential diagnosis of dementia. Overall the diagnosis of dementia can be improved by using parameters from MR spectroscopy. This article focuses on MR spectroscopic changes in the physiological aging process as well as on changes in mild cognitive impairment a precursor of Alzheimer's dementia, in Alzheimer's dementia, frontotemporal dementia, vascular dementia and Lewy body dementia.

EULAR recommendations for the management of large vessel vasculitis.

OBJECTIVES: To develop European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis. METHODS: An expert group (10 rheumatologists, 3 nephrologists, 2 immunolgists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search through a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of large vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. RESULTS: Seven recommendations were made relating to the assessment, investigation and treatment of patients with large vessel vasculitis. The strength of recommendations was restricted by the low level of evidence and EULAR standardised operating procedures. CONCLUSIONS: On the basis of evidence and expert consensus, management recommendations for large vessel vasculitis have been formulated and are commended for use in everyday clinical practice.

EULAR recommendations for the management of primary small and medium vessel vasculitis.

OBJECTIVES: To develop European League Against Rheumatism (EULAR) recommendations for the management of small and medium vessel vasculitis. METHODS: An expert group (consisting of 10 rheumatologists, 3 nephrologists, 2 immunologists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search using a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of small and medium vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. RESULTS: In all, 15 recommendations were made for the management of small and medium vessel vasculitis. The strength of recommendations was restricted by low quality of evidence and by EULAR standardised operating procedures. CONCLUSIONS: On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice.