Search

Background and Purpose: Radiation-induced damage to the organs at risk (OARs) in head-and-neck cancer (HNC) patient can result in long-term complications. Quantitative magnetic resonance imaging (qMRI) techniques such as diffusion-weighted imaging (DWI), DIXON for fat fraction (FF) estimation and T2 mapping could potentially provide a spatial assessment of such damage. The goal of this study is to validate these qMRI techniques in terms of accuracy in phantoms and repeatability in-vivo across a broad selection of healthy OARs in the HN region. Materials and Methods: Scanning was performed at a 3 T diagnostic MRI scanner, including the calculation of apparent diffusion coefficient (ADC) from DWI, FF and T2 maps. Phantoms were scanned to estimate the qMRI techniques bias using Bland-Altman statistics. Twenty-six healthy subjects were scanned twice in a test–retest study to determine repeatability. Repeatability coefficients (RC) were calculated for the parotid, submandibular, sublingual and tubarial salivary glands, oral cavity, pharyngeal constrictor muscle and brainstem. Additionally, a linear mixed-effect model analysis was used to evaluate the effect of subject-specific characteristics on the qMRI values. Results: Bias was 0.009x10-3 mm2/s for ADC, -0.7 % for FF and -7.9 ms for T2. RCs ranged 0.11–0.25x10-3 mm2/s for ADC, 1.2–6.3 % for FF and 2.5–6.3 ms for T2. A significant positive linear relationship between age and the FF and T2 for some of the OARs was found. Conclusion: These qMRI techniques are feasible, accurate and repeatable, which is promising for treatment response monitoring and/or differentiating between healthy and unhealthy tissues due to radiation-induced damage in HNC patients.

Interactions of cosmic ray protons, atomic nuclei, and electrons in the interstellar medium in the inner part of the Milky Way produce a γ-ray flux from the Galactic Ridge. If the γ-ray emission is dominated by proton and nuclei interactions, a neutrino flux comparable to the γ-ray flux is expected from the same sky region.Data collected by the ANTARES neutrino telescope are used to constrain the neutrino flux from the Galactic Ridge in the 1-100 TeV energy range. Neutrino events reconstructed both as tracks and showers are considered in the analysis and the selection is optimized for the search of an excess in the region |l|

This letter presents a combined measurement of the energy spectra of atmospheric νe and νμ in the energy range between ∼100 GeV and ∼50 TeV with the ANTARES neutrino telescope. The analysis uses 3012 days of detector livetime in the period 2007–2017, and selects 1016 neutrinos interacting in (or close to) the instrumented volume of the detector, yielding shower-like events (mainly from νe+ν‾e charged current plus all neutrino neutral current interactions) and starting track events (mainly from νμ+ν‾μ charged current interactions). The contamination by atmospheric muons in the final sample is suppressed at the level of a few per mill by different steps in the selection analysis, including a Boosted Decision Tree classifier. The distribution of reconstructed events is unfolded in terms of electron and muon neutrino fluxes. The derived energy spectra are compared with previous measurements that, above 100 GeV, are limited to experiments in polar ice and, for νμ, to Super-Kamiokande.

Neutrino detectors participate in the indirect search for the fundamental constituents of dark matter (DM) in form of weakly interacting massive particles (WIMPs). In WIMP scenarios, candidate DM particles can pair-annihilate into Standard Model products, yielding considerable fluxes of high-energy neutrinos. A detector like ANTARES, located in the Northern Hemisphere, is able to perform a complementary search looking towards the Galactic Centre, where a high density of dark matter is thought to accumulate. Both this directional information and the spectral features of annihilating DM pairs are entered into an unbinned likelihood method to scan the data set in search for DM-like signals in ANTARES data. Results obtained upon unblinding 3170 days of data reconstructed with updated methods are presented, which provides a larger, and more accurate, data set than a previously published result using 2101 days. A non-observation of dark matter is converted into limits on the velocity-averaged cross section for WIMP pair annihilation.

Using data recorded with the ANTARES telescope from 2007 to 2015, a new search for dark matter annihilation in the Milky Way has been performed. Three halo models and five annihilation channels, WIMP+WIMP→bb¯,W+W−,τ+τ−,μ+μ− and νν¯, with WIMP masses ranging from 50 GeVc2 to 100 TeVc2, were considered. No excess over the expected background was found, and limits on the thermally averaged annihilation cross-section were set.

A highly significant excess of high-energy astrophysical neutrinos has been reported by the IceCube Collaboration. Some features of the energy and declination distributions of IceCube events hint at a North/South asymmetry of the neutrino flux. This could be due to the presence of the bulk of our Galaxy in the Southern hemisphere. The ANTARES neutrino telescope, located in the Mediterranean Sea, has been taking data since 2007. It offers the best sensitivity to muon neutrinos produced by galactic cosmic ray interactions in this region of the sky. In this letter a search for an extended neutrino flux from the Galactic Ridge region is presented. Different models of neutrino production by cosmic ray propagation are tested. No excess of events is observed and upper limits for different neutrino flux spectral indices Γ are set. For Γ=2.4 the 90% confidence level flux upper limit at 100 TeV for one neutrino flavour corresponds to Φ01f(100 TeV)=2.0⋅10−17 GeV−1cm−2s−1sr−1. Under this assumption, at most two events of the IceCube cosmic candidates can originate from the Galactic Ridge. A simple power-law extrapolation of the Fermi-LAT flux to account for IceCube High Energy Starting Events is excluded at 90% confidence level.

A search for muon neutrinos originating from dark matter annihilations in the Sun is performed using the data recorded by the ANTARES neutrino telescope from 2007 to 2012. In order to obtain the best possible sensitivities to dark matter signals, an optimisation of the event selection criteria is performed taking into account the background of atmospheric muons, atmospheric neutrinos and the energy spectra of the expected neutrino signals. No significant excess over the background is observed and 90% C.L. upper limits on the neutrino flux, the spin-dependent and spin-independent WIMP-nucleon cross-sections are derived for WIMP masses ranging from 50 GeV to 5 TeV for the annihilation channels WIMP+WIMP→bb¯,W+W− and τ+τ−.

Background: Hyperkinetic movement disorders (HMD) manifest as abnormal and uncontrollable movements. Despite reported involvement of several neural circuits, exact connectivity profiles remain elusive. Objectives: Providing a comprehensive literature review of resting-state brain connectivity alterations using resting-state fMRI (rs-fMRI). We additionally discuss alterations from the perspective of brain networks, as well as correlations between connectivity and clinical measures. Methods: A systematic review was performed according to PRISMA guidelines and searching PubMed until October 2022. Rs-fMRI studies addressing ataxia, chorea, dystonia, myoclonus, tics, tremor, and functional movement disorders (FMD) were included. The standardized mean difference was used to summarize findings per region in the Automated Anatomical Labeling atlas for each phenotype. Furthermore, the activation likelihood estimation meta-analytic method was used to analyze convergence of significant between-group differences per phenotype. Finally, we conducted hierarchical cluster analysis to provide additional insights into commonalities and differences across HMD phenotypes. Results: Most articles concerned tremor (51), followed by dystonia (46), tics (19), chorea (12), myoclonus (11), FMD (11), and ataxia (8). Altered resting-state connectivity was found in several brain regions: in ataxia mainly cerebellar areas; for chorea, the caudate nucleus; for dystonia, sensorimotor and basal ganglia regions; for myoclonus, the thalamus and cingulate cortex; in tics, the basal ganglia, cerebellum, insula, and frontal cortex; for tremor, the cerebello-thalamo-cortical circuit; finally, in FMD, frontal, parietal, and cerebellar regions. Both decreased and increased connectivity were found for all HMD. Significant spatial convergence was found for dystonia, FMD, myoclonus, and tremor. Correlations between clinical measures and resting-state connectivity were frequently described. Conclusion: Key brain regions contributing to functional connectivity changes across HMD often overlap. Possible increases and decreases of functional connections of a specific region emphasize that HMD should be viewed as a network disorder. Despite the complex interplay of physiological and methodological factors, this review serves to gain insight in brain connectivity profiles across HMD phenotypes.

Background: Brain imaging with [18F]FDG-PET can support the diagnostic work-up of patients with α-synucleinopathies. Validated data analysis approaches are necessary to evaluate disease-specific brain metabolism patterns in neurodegenerative disorders. This study compared the univariate Statistical Parametric Mapping (SPM) single-subject procedure and the multivariate Scaled Subprofile Model/Principal Component Analysis (SSM/PCA) in a cohort of patients with α-synucleinopathies. Methods: We included [18F]FDG-PET scans of 122 subjects within the α-synucleinopathy spectrum: Parkinson’s Disease (PD) normal cognition on long-term follow-up (PD – low risk to dementia (LDR); n = 28), PD who developed dementia on clinical follow-up (PD – high risk of dementia (HDR); n = 16), Dementia with Lewy Bodies (DLB; n = 67), and Multiple System Atrophy (MSA; n = 11). We also included [18F]FDG-PET scans of isolated REM sleep behaviour disorder (iRBD; n = 51) subjects with a high risk of developing a manifest α-synucleinopathy. Each [18F]FDG-PET scan was compared with 112 healthy controls using SPM procedures. In the SSM/PCA approach, we computed the individual scores of previously identified patterns for PD, DLB, and MSA: PD-related patterns (PDRP), DLBRP, and MSARP. We used ROC curves to compare the diagnostic performances of SPM t-maps (visual rating) and SSM/PCA individual pattern scores in identifying each clinical condition across the spectrum. Specifically, we used the clinical diagnoses (“gold standard”) as our reference in ROC curves to evaluate the accuracy of the two methods. Experts in movement disorders and dementia made all the diagnoses according to the current clinical criteria of each disease (PD, DLB and MSA). Results: The visual rating of SPM t-maps showed higher performance (AUC: 0.995, specificity: 0.989, sensitivity 1.000) than PDRP z-scores (AUC: 0.818, specificity: 0.734, sensitivity 1.000) in differentiating PD-LDR from other α-synucleinopathies (PD-HDR, DLB and MSA). This result was mainly driven by the ability of SPM t-maps to reveal the limited or absent brain hypometabolism characteristics of PD-LDR. Both SPM t-maps visual rating and SSM/PCA z-scores showed high performance in identifying DLB (DLBRP = AUC: 0.909, specificity: 0.873, sensitivity 0.866; SPM t-maps = AUC: 0.892, specificity: 0.872, sensitivity 0.910) and MSA (MSARP: AUC: 0.921, specificity: 0.811, sensitivity 1.000; SPM t-maps: AUC: 1.000, specificity: 1.000, sensitivity 1.000) from other α-synucleinopathies. PD-HDR and DLB were comparable for the brain hypo and hypermetabolism patterns, thus not allowing differentiation by SPM t-maps or SSM/PCA. Of note, we found a gradual increase of PDRP and DLBRP expression in the continuum from iRBD to PD-HDR and DLB, where the DLB patients had the highest scores. SSM/PCA could differentiate iRBD from DLB, reflecting specifically the differences in disease staging and severity (AUC: 0.938, specificity: 0.821, sensitivity 0.941). Conclusions: SPM-single subject maps and SSM/PCA are both valid methods in supporting diagnosis within the α-synucleinopathy spectrum, with different strengths and pitfalls. The former reveals dysfunctional brain topographies at the individual level with high accuracy for all the specific subtype patterns, and particularly also the normal maps; the latter provides a reliable quantification, independent from the rater experience, particularly in tracking the disease severity and staging. Thus, our findings suggest that differences in data analysis approaches exist and should be considered in clinical settings. However, combining both methods might offer the best diagnostic performance.

Spinocerebellar ataxia type 3 (SCA3) is a rare genetic neurodegenerative disease. The neurobiological basis of SCA3 is still poorly understood, and up until now resting-state fMRI (rs-fMRI) has not been used to study this disease. In the current study we investigated (multi-echo) rs-fMRI data from patients with genetically confirmed SCA3 (n = 17) and matched healthy subjects (n = 16). Using independent component analysis (ICA) and subsequent regression with bootstrap resampling, we identified a pattern of differences between patients and healthy subjects, which we coined the fMRI SCA3 related pattern (fSCA3-RP) comprising cerebellum, anterior striatum and various cortical regions. Individual fSCA3-RP scores were highly correlated with a previously published 18F-FDG PET pattern found in the same sample (rho = 0.78, P = 0.0003). Also, a high correlation was found with the Scale for Assessment and Rating of Ataxia scores (r = 0.63, P = 0.007). No correlations were found with neuropsychological test scores, nor with levels of grey matter atrophy. Compared with the 18F-FDG PET pattern, the fSCA3-RP included a more extensive contribution of the mediofrontal cortex, putatively representing changes in default network activity. This rs-fMRI identification of additional regions is proposed to reflect a consequence of the nature of the BOLD technique, enabling measurement of dynamic network activity, compared to the more static 18F-FDG PET methodology. Altogether, our findings shed new light on the neural substrate of SCA3, and encourage further validation of the fSCA3-RP to assess its potential contribution as imaging biomarker for future research and clinical use.

Mangroves play an important role in protecting coasts against wave energy and storms. Mangrove ecosystems provide important habitats for fauna and flora and are an important carbon sink. Loss of mangroves forest may lead to enhanced coastal erosion. Mangroves are complex ecosystems and processes of settling and development are not fully understood. Characterizing the rates and patterns of mangrove gains and losses is needed to better understand the functioning of mangrove ecosystems, how mangrove dynamics are linked to coastal morphological behaviour and how human interference with the coastal system impacts mangroves. Here we present a study of the mangrove ecosystems at the Suriname coast, which are relatively pristine and characterized by strong dynamics due to migrating mudbanks along the coast. Satellite images between 2000 and 2018, available in the historic satellite image archives, were analysed using the LandTrendr (Landsat-based detection of trends in disturbance and recovery) algorithm to identify locations of mangrove erosion, mangrove colonization, surface areas of change and patterns of settlement, as indicated by (sudden) changes in NDVI. The algorithm requires careful setting of various parameters for successful detection of (abrupt) temporal changes in mangrove coverage. The algorithm was evaluated on its robustness using various parameter settings. Results show the value of the timeseries of Landsat imagery to detect locations of coastal erosion of up to 50 m/yr and accretion where loss or settlement of mangroves is prevailing between 2000 and 2018. Locally differences are very large. An overall westward mangrove progression along the coast is apparent from the images and probably linked to mud bank migration. Various patterns of mangrove colonization and development such as arc-, zonal- and patch- arrangements were identified, although at some locations the Landsat resolution of 30 m is somewhat coarse to allow detailed analysis. The success and robustness of the LandTrendr algorithm are controlled by NDVI threshold values, number of allowed breakpoints in the timeseries and fitting parameters. The presented method requires further testing and evaluation but is a promising tool for semi-automatic detection of coastal mangrove erosion and colonization that can be applied to other mangrove ecosystems in the world. The satellite timeseries analyses generate valuable information on coastal dynamics, which is helpful to identify coastal areas prone to erosion and mangrove retreat and provide as such a valuable tool for coastal management and protection.

Mapping of subtidal banks in mud-dominated coastal systems is crucial as they influence not only shoreline and ecosystem dynamics but also economic activities and livelihoods of local communities. Due to associated spatiotemporal variations in suspended particulate matter concentrations, subtidal mudbanks are often confined by diffuse and rapidly changing boundaries. To avoid inaccurate representations of these mudbanks in remote sensing images, it is necessary to unmix distinctive reflectance signals into representative landcover fractions. Yet, extracting mud fractions, in order to characterize such diffuse boundaries, is challenging because of the spectral similarity between subtidal- and intertidal features. Here we show that an unsupervised decision tree, used to derive spatially explicit and spectrally coherent image endmembers, facilitates robust linear spectral unmixing on an image-to-image basis, enabling the separation of these coastal features. We found that resulting abundance maps represent cross-shore gradients of vegetation, water and mud fractions present at the coast of Suriname. Furthermore, we confirmed that it is possible to separate land, water and an initial estimate of intertidal zones on individual images. Thus, spectral signatures of end-member candidates, determined from relevant index histograms within these initial estimates, are consistent. These results demonstrate that spectral information from well-defined spatial neighbourhoods facilitates the detection of diffuse boundaries of mudbanks with a spectral unmixing approach.

Scaled subprofile model using principal component analysis (SSM/PCA) is a multivariate analysis technique used, mainly in [18F]-2-fluoro-2-deoxy-d-glucose (FDG) PET studies, for the generation of disease-specific metabolic patterns (DP) that may aid with the classification of subjects with neurological disorders, like Alzheimer’s disease (AD). The aim of this study was to explore the feasibility of using quantitative parametric images for this type of analysis, with dynamic [11C]-labelled Pittsburgh Compound B (PIB) PET data as an example. Therefore, 15 AD patients and 15 healthy control subjects were included in an SSM/PCA analysis to generate four AD-DPs using relative cerebral blood flow (R1), binding potential (BPND) and SUVR images derived from dynamic PIB and static FDG-PET studies. Furthermore, 49 new subjects with a variety of neurodegenerative cognitive disorders were tested against these DPs. The AD-DP was characterized by a reduction in the frontal, parietal, and temporal lobes voxel values for R1 and SUVR-FDG DPs; and by a general increase of values in cortical areas for BPND and SUVR-PIB DPs. In conclusion, the results suggest that the combination of parametric images derived from a single dynamic scan might be a good alternative for subject classification instead of using 2 independent PET studies.

Efficient water-resource management is essential with regard to food security, growing populations and climate change. This is especially important for low- and middle-income (LMC) countries where food is often locally produced by traditional smallholder farming. Detailed knowledge of the spatio-temporal distribution of irrigation-water consumption provides valuable information to anticipate local food shortages and water scarcity as a result of climate variability. Yet, adequate techniques to quantify irrigation-water consumption at field level over large areas are lacking. Irrigation estimates generally have a coarse resolution making them inadequate for field-level assessments.This study developed a remote-sensing-based approach to quantify spatio-temporal patterns of irrigation-water consumption at field level using the MODIS evapotranspiration product (MOD16A2) and existing land-use maps on the spatio-temporal distribution of irrigated agriculture. Object-based image analysis was used to establish local evapotranspiration differences between irrigated and rainfed fields on a monthly basis, which are the irrigation-water consumption rates of the irrigated fields. This novel method was applied to a study area in the Central Rift Valley in Ethiopia where smallholder farming is dominant and only a few large-scale farms are present. Comparison with irrigation-water-consumption values of a local irrigation scheme showed that the monthly temporal dynamics were captured quite well, but lower values were calculated compared to the scheme's field data. Comparison with two validated remote-sensing based studies in Africa showed good agreement as irrigation-water-consumption estimates were in the same order of magnitude. Irrigation-water consumption follows the temporal rainfall pattern, i.e. irrigation practices intensify with increased water availability. Surface water is commonly used for irrigation in the study area.Our study shows that smallholder practices have a lower irrigation-water consumption compared to modern large-scale farms by approximately a factor 3. Irrigation-water consumption in the area is considerable, especially during the dry season. On average 32 % of excess water (precipitation – evapotranspiration) is consumed for irrigation. For smallholder irrigation and large-scale irrigation specifically this is 28 % and 63 % respectively.The object-based approach presented here is an operational mapping method for field-level irrigation-water-consumption over large areas. MOD16A2 is a global open-source readily-available evapotranspiration product used here although an evapotranspiration product with a higher spatial resolution might be preferred. Our approach can provide irrigation-water-consumption estimates over large areas in data-poor regions, which will increase the understanding of spatio-temporal patterns of smallholder irrigation and provide information to optimize water use.

Introduction: We aimed to uncover the pattern of network-level changes in neuronal function in Spinocerebellar ataxia type 3 (SCA3). Methods: 17 genetically-confirmed SCA3 patients and 16 controls underwent structural MRI and static resting-state [18F]‑Fluoro‑deoxyglucose Positron Emission Tomography (FDG-PET) imaging. A SCA3-related pattern (SCA3-RP) was identified using a multivariate method (scaled subprofile model and principal component analysis (SSM PCA)). Participants were evaluated with the Scale for Assessment and Rating of Ataxia (SARA) and with neuropsychological examination including tests for language, executive dysfunction, memory, and information processing speed. The relationships between SCA3-RP expression and clinical scores were explored. Voxel based morphology (VBM) was applied on MRI-T1 images to assess possible correlations between FDG reduction and grey matter atrophy. Results: The SCA3-RP disclosed relative hypometabolism of the cerebellum, caudate nucleus and posterior parietal cortex, and relatively increased metabolism in somatosensory areas and the limbic system. This topography, which was not explained by regional atrophy, correlated significantly with ataxia (SARA) scores (ρ = 0.72; P = 0.001). SCA3 patients showed significant deficits in executive function and information processing speed, but only letter fluency correlated with SCA3-RP expression (ρ = 0.51; P = 0.04, uncorrected for multiple comparisons). Conclusion: The SCA3 metabolic profile reflects network-level alterations which are primarily associated with the motor features of the disease. Striatum decreases additional to cerebellar hypometabolism underscores an intrinsic extrapyramidal involvement in SCA3. Cerebellar-posterior parietal hypometabolism together with anterior parietal (sensory) cortex hypermetabolism may reflect a shift from impaired feedforward to compensatory feedback processing in higher-order motor control. The demonstrated SCA3-RP provides basic insight in cerebral network changes in this disease. Keywords: Spinocerebellar ataxia type 3, Neuroimaging, Cerebellum, FDG-PET, Networks

We manually detected and mapped 66 landslides from Landsat imagery over a 33-year period from 1985 to 2017 in the Buckinghorse River region, British Columbia, Canada. We semi-automatically determined landslide timing using the cumulative difference (CD) between the normalized difference vegetation index (NDVI) and a fitted harmonic sinusoidal curve (CDNDVI). The semi-automated dating method was capable of determining the timing of 80% of the landslides using CDNDVI and 85% of the landslides after detrending CDNDVI (dCDNDVI). The CDNDVI method generally detects landslides too early and the dCDNDVI method is generally too late. Mean absolute errors (in days) are lower for the dCDNDVI (208 and 188) than the CDNDVI (227 and 267), respectively. This study, however, has many examples of extreme outliers with very large errors (>1000 days). Our method is portable to other remote regions as long as vegetation anomalies can be used as an indicator for landslide activity. We conclude that the timeseries of images available in the Landsat Archive are useful for landslide mapping, but the pixel size limits the size of the landslides that can be mapped.

This exploratory study set out to investigate dynamic functional connectivity (dFC) in patients with jerky and tremulous functional movement disorders (JT-FMD). The focus in this work is on dynamic brain states, which represent distinct dFC patterns that reoccur in time and across subjects. Resting-state fMRI data were collected from 17 patients with JT-FMD and 17 healthy controls (HC). Symptom severity was measured using the Clinical Global Impression-Severity scale. Depression and anxiety were measured using the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), respectively. Independent component analysis was used to extract functional brain components. After computing dFC, dynamic brain states were determined for every subject using k-means clustering. Compared to HC, patients with JT-FMD spent more time in a state that was characterized predominantly by increasing medial prefrontal, and decreasing posterior midline connectivity over time. They also tended to visit this state more frequently. In addition, patients with JT-FMD transitioned significantly more often between different states compared to HC, and incorporated a state with decreasing medial prefrontal, and increasing posterior midline connectivity in their attractor, i.e., the cyclic patterns of state transitions. Altogether, this is the first study that demonstrates altered functional brain network dynamics in JT-FMD that may support concepts of increased self-reflective processes and impaired sense of agency as driving factors in FMD.

Background: Essential tremor (ET) is one of the most common hyperkinetic movement disorders. Previous research into the pathophysiology of ET suggested underlying cerebellar abnormalities. Objective: In this study, we added electromyography as an index of tremor intensity to functional Magnetic Resonance Imaging (EMG-fMRI) to study a group of ET patients selected according to strict criteria to achieve maximal homogeneity. With this approach we expected to improve upon the localization of the bilateral cerebellar abnormalities found in earlier fMRI studies. Methods: We included 21 propranolol sensitive patients, who were not using other tremor medication, with a definite diagnosis of ET defined by the Tremor Investigation Group. Simultaneous EMG-fMRI recordings were performed while patients were off tremor medication. Patients performed unilateral right hand and arm extension, inducing tremor, alternated with relaxation (rest). Twenty-one healthy, age- and sex-matched participants mimicked tremor during right arm extension. EMG power variability at the individual tremor frequency as a measure of tremor intensity variability was used as a regressor, mathematically independent of the block regressor, in the general linear model used for fMRI analysis, to find specific tremor-related activations. Results: Block-related activations were found in the classical upper-limb motor network, both for ET patients and healthy participants in motor, premotor and supplementary motor areas. In ET patients, we found tremor-related activations bilaterally in the cerebellum: in left lobules V, VI, VIIb and IX and in right lobules V, VI, VIIIa and b, and in the brainstem. In healthy controls we found simulated tremor-related activations in right cerebellar lobule V. Conclusions: Our results expand on previous findings of bilateral cerebellar involvement in ET. We have identified specific areas in the bilateral somatomotor regions of the cerebellum: lobules V, VI and VIII.

Introduction: In this retrospective study concerning patients with Parkinson's disease (PD) scanned with 18-F-Dopa PET (N = 129), we looked for an association between reduced 18-F-Dopa uptake and the key PD symptoms tremor and hypokinesia-rigidity. We hypothesized to find a stronger correlation between dopaminergic depletion in the striatum and hypokinesia-rigidity compared to tremor. Methods: The onset side of symptoms (documented for 102 patients) as well as the first registered UPDRS (available for 79 patients) was used to correlate with F-Dopa uptake values in the caudate nucleus and putamen in this large retrospective sample. Results: Reduced F-Dopa uptake was contralateral to hypokinesia-rigidity symptoms and correlated with its severity (quantified by UPDRS). For tremor severity, no correlation was seen with F-Dopa reduction. Furthermore, freezing of gait correlated with reduced F-Dopa uptake in the putamen of the right hemisphere. Conclusion and discussion: Our results, obtained in a large patient group, provides support for the concept that tremor in PD is not only based on a dopamine related pathway but may rely on a different pathway.

Introduction: Under normal conditions, the spatial distribution of resting cerebral blood flow and cerebral metabolic rate of glucose are closely related. A relatively new magnetic resonance (MR) technique, pseudo-continuous arterial spin labeling (PCASL), can be used to measure regional brain perfusion. We identified a Parkinson's disease (PD)-related perfusion and metabolic covariance pattern in the same patients using PCASL and FDG-PET imaging and assessed (dis)similarities in the disease-related pattern between perfusion and metabolism in PD patients. Methods: Nineteen PD patients and seventeen healthy controls underwent [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. Of 14 PD patients and all healthy controls PCASL-MRI could be obtained. Data were analyzed using scaled subprofile model/principal component analysis (SSM/PCA). Results: Unique Parkinson's disease-related perfusion and metabolic covariance patterns were identified using PCASL and FDG-PET in the same patients. The PD-related metabolic covariance brain pattern is in high accordance with previously reports. Also our disease-related perfusion pattern is comparable to the earlier described perfusion pattern. The most marked difference between our perfusion and metabolic patterns is the larger perfusion decrease in cortical regions including the insula. Conclusion: We identified PD-related perfusion and metabolic brain patterns using PCASL and FDG-PET in the same patients which were comparable with results of existing research. In this respect, PCASL appears to be a promising addition in the early diagnosis of individual parkinsonian patients.

Background: Hemophilia care has improved greatly because of advances in treatment options and comprehensive care. In-depth insight into the perspectives of persons with hemophilia and health care providers on their care may provide targets for further improvements., Objectives: To assess satisfaction of the hemophilia population with their care, to explore factors determining care satisfaction, and to identify areas for potential health care improvements, including digital health tools., Methods: First, to assess care satisfaction and factors determining satisfaction and health care improvements, data from a nationwide, cross-sectional questionnaire among 867 adult and pediatric Dutch persons with hemophilia A or B were analyzed. This included the Hemophilia Patient Satisfaction Scale questionnaire, Canadian Hemophilia Outcomes Kids' Life Assessment Tool satisfaction questions, a visual analog scale satisfaction score, and open questions. Second, to further explore factors determining satisfaction and health care improvements, semistructured interviews were conducted with 19 persons with hemophilia or their parents and 18 health care providers., Results: High care satisfaction was found, with an overall median Hemophilia Patient Satisfaction Scale score of 12 (IQR, 6-21). Participants in the interviews reported that patient-professional interactions, availability of care, and coordination of care were major factors determining satisfaction. Suggested health care improvements included improved information provision and coordination of care, especially shared care with professionals not working within comprehensive care centers. Participants suggested that digital health tools could aid in this., Conclusion: Satisfaction with hemophilia care is high among persons with hemophilia in the Netherlands, although several potential improvements have been identified. Accentuating these is especially relevant in the current era of treatment innovations, in which we might focus less on other aspects of care., (© 2023 The Author(s).)

Purpose: Treatment of Prostate Cancer (PCa) with Androgen Deprivation Therapy (ADT) involves long-term consequences including bone loss and fractures. Our aim was to evaluate the calculated fracture risk and the prevalence of osteoporosis, vertebral fractures (VF) and sarcopenia in men with PCa at initiation of ADT, as ADT will increase fracture risk from that moment onward., Methods: In this cross-sectional real-world study in men at ADT initiation, fracture risk factors including comorbidities, medication, and 10-year fracture risk (FRAX®) were assessed. Laboratory tests, dual-energy X-ray absorptiometry, and spinal X-rays were performed. Sarcopenia was defined according to EWGSOP2., Results: In 115 men at ADT initiation, aged 73.3 (±7.6) years, osteoporosis was diagnosed in 4.3 % and osteopenia in 35.7 %. The mean 10-year fracture risk of major osteoporotic fracture was 4.4 % and of hip fracture 1.7 %, respectively. At least one VF was present in 32.2 % and 33.9 % of men had osteoporosis and/or a VF assessed on spinal X-rays. In 10.4 % at least one new fracture-risk-associated metabolic bone disorder was diagnosed with laboratory testing. Sarcopenia was diagnosed in only one patient., Conclusions: Although the prevalence of osteoporosis, sarcopenia and 10-years fracture risk is low, there is a high prevalence of vertebral fractures in a third of the men with PCa at the time of ADT initiation. Besides a BMD measurement and fracture risk calculation using FRAX, a systematic vertebral fracture assessment should be considered in all men with PCa at initiation of ADT to provide a reliable baseline classification of VFs to improve identification of true incident VFs during ADT., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marsha van Oostwaard, Dr. Yes van de Wouw, Professor dr. Maryska Janssen-Heijnen, Dr. Marc de Jong and Dr. Caroline Wyers have no conflicts of interest. Professor dr. Joop van den Bergh reports consulting fees and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Amgen institution and UCB institution outside the submitted work., (© 2022 The Authors.)

Peptide receptor radionuclide therapy (PRRT) is used for the treatment of patients with unresectable or metastasized somatostatin receptor type 2 (SSTR 2 )-expressing gastroenteropancreatic neuroendocrine tumours (GEP-NETs). The radiolabelled somatostatin analogue [ 177 Lu]Lu-DOTA-TATE delivers its radiation dose to SSTR 2 -overexpressing tumour cells, resulting in selective cell killing during radioactive decay. While tumour control can be achieved in many patients, complete remissions remain rare, causing the majority of patients to relapse after a certain period of time. This raises the question whether the currently fixed treatment regime (4 × 7.4 GBq) leaves room for dose escalation as a means of improving therapy efficacy. The kidneys have shown to play an important role in defining a patient's tolerability to PRRT. As a consequence of the proximal tubular reabsorption of [ 177 Lu]Lu-DOTA-TATE, via the endocytic megalin/cubilin receptor complex, the radionuclides are retained in the renal interstitium. This results in extended retention of radioactivity in the kidneys, generating a risk for the development of radiation nephropathy. In addition, a decreased kidney function has shown to be associated with a prolonged circulation of [ 177 Lu]Lu-DOTA-TATE, causing increased irradiation to the bone marrow. This can on its turn lead to myelosuppression and haematological toxicity, owing to the marked radio sensitivity of the rapidly proliferating cells in the bone marrow. In contrast to external beam radiotherapy (EBRT), the exact absorbed dose limits for these critical organs (kidneys and bone marrow) in PRRT with [ 177 Lu]Lu-DOTA-TATE are still unclear. Better insights into these uncertainties, can help in optimizing PRRT to reach its maximum therapeutic potential, while avoiding severe adverse events, like nephropathy and hematologic toxicities. In this review we focus on the nephrotoxic effects of PRRT with [ 177 Lu]Lu-DOTA-TATE for the treatment of GEP-NETs. If the absorbed dose to the kidneys can be lowered, higher activities can be administered, enlarging the therapeutic window for PRRT. Therefore, we evaluated the renal protective potential of current and promising future strategies and discuss the importance of (renal) dosimetry in PRRT., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Paludiculture, the cultivation of crops on rewetted peatlands, is often proposed as a viable climate change mitigation option that reduces greenhouse gas emissions (GHGe), while simultaneously providing novel agricultural business options. In West Europe, experiments are ongoing in using the paludicrop cattail (Typha spp.) as feedstock for insulation panel material. Here, we use a Dutch case study to investigate the environmental potential and economic viability of shifting the use of peat soils from grassland (for dairy production) to Typha paludiculture (for cultivation and insulation panel production). Using a life cycle assessment and cost-benefit analysis, we compared the global warming potential (GWP), yearly revenues and calculated Net Present Value (NPV) of 1 ha Dutch peat soil used either for dairy production or for Typha paludiculture. We estimated that changing to Typha paludiculture leads to a GWP reduction of ~32% (16.4 t CO 2 -eq ha -1 ), mainly because of lower emissions from peat decomposition as a result of land-use management (-21.6 t CO 2 -eq ha -1 ). If biogenic carbon storage is excluded, the avoided impact of conventional insulation material is insufficient to compensate the impact of cultivating and processing Typha (9.7 t CO 2 -eq ha -1 ); however, this changes if biogenic carbon storage is included (following PAS2050 guidelines). Typha paludiculture is currently not competitive with dairy production, mainly due to high cultivation costs and low revenues, which are both uncertain, and will likely improve as the system develops. Its NPV is negative, mainly due to high investment costs. This can be improved by introducing carbon credits, with carbon prices for Typha paludiculture (30 years) comparable to EU-ETS prices. In conclusion, Dutch Typha paludiculture has a significant climate change mitigation potential by reducing emissions from deep drained peatlands. Nevertheless, attention is needed to increase its economic viability as this is a key aspect of the system change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Providing a second opinion (SO) in oncology is complex, and communication during SOs remains poorly understood. This study aimed to systematically observe how patients and oncologists communicate about SO-specific topics (i.e., patient motivation, the referring oncologist, treatment transfer/back-referral), and how such communication affects patient satisfaction., Methods: A prospective mixed-methods study of cancer patients seeking a SO (N = 69) and consulting oncologists was conducted. Before the SO, patients reported their expected place of future treatment. Following the SO, patients' and oncologists' satisfaction was assessed. All SOs were audio-recorded. Absolute and relative duration of SO-specific talk were calculated and specific events (e.g., questions/utterances) were coded (incl. valence, explicitness)., Results: SOs lasted 19-73 min, of which 3.7% was spent discussing motivations. Oncologists rarely explored patients' motivations. Talk about referring oncologists (12.5% of consultation) was mostly critical by patients (M = 43.0%), but positive/confirming by consulting oncologists (M = 73.5%). Although 22.2% of patients expected a treatment transfer, this topic (3.3% of consultation time) was rarely explicitly discussed. Patients who were referred back were significantly less satisfied (d = 0.85)., Conclusion: Patient-provider communication in oncological SOs appears insufficiently aligned., Practice Implications: Patients and oncologists need support to explicitly and productively communicate about SO-specific topics and to better manage expectations. Recommendations are provided., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Bridging the gap between complex signal data output and clear interpretation by non-expert end-users is a major challenge many scientists face when converting their scientific technology into a real-life application. Currently, pattern recognition algorithms are the most frequently encountered signal data interpretation algorithms to close this gap, not in the least because of their straight-forward implementation via convenient software packages. Paradoxically, just because their implementation is so straight-forward, it becomes cumbersome to integrate the expert's domain-specific knowledge. In this work, a novel signal data interpretation approach is presented that uses this domain-specific knowledge as its fundament, thereby fully exploiting the unique expertise of the scientist. The new approach applies data preprocessing in an innovative way that transcends its usual purpose and is easy to translate into a software application. Multiple case studies illustrate the straight-forward application of the novel approach. Ultimately, the approach is highly suited for integration in various (bio)analytical applications that require interpretation of signal data., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: This meta-analysis investigates MR recurrence and degree of left ventricular reverse remodeling (LVRR) in CIMR patients in mitral annuloplasty employing different ring designs., Background: The deeper understanding of complex changes caused by chronic ischemic mitral regurgitation (CIMR) have led to new generations of rings that, by maintaining normal 3D annular geometry are supposed to enhance long-term repair durability., Methods: A meta-analysis of all available reports in literature of MV repair through different ring design was conducted. Meta-regression was performed to investigate the impact of mitral ring characteristics related to flexibility, planarity, symmetry and single type utilized. Twenty studies encompassing a total of 1876 patients were included at the end of the selection process., Results: At meta-regression recurrence of MR was not influenced by the ring employed. Nonetheless, the event rate of MR recurrence in planar rings was 19%. Vs. 11% observed with non-planar rings. Recurrence rate in patients implanted with symmetric rings was 14% whereas it was 7% in asymmetric rings. The non-planar asymmetric IMR-ETlogix showed the lowest recurrence rate (6%). Furthermore, in planar group the reduction of pre- and post-operative LVEDD was - 4%. In the non-planar group, the LVEDD was reduced by 8.6%. In patients implanted with symmetric rings LVEDD reduction was 10.8%. LVRR in the asymmetric group was -5.8%., Conclusion: MR recurrence occurred the least with asymmetric rings with less disproportionate asymmetry. In contrast, LVRR occurred at a greater extent in symmetric rings., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Most organisms have an endogenous circadian clock with a period length of approximately 24 h that enables adaptation, synchronization and anticipation to environmental cycles. The circadian system (circa = about or around, diem = a day) may provide evolutionary benefits when entrained to the 24-h light-dark cycle. The more the internal circadian period (τ) deviates from the external light-dark cycle, the larger the daily phase shifts need to be to synchronize to the environment. In some species, large daily phase shifts reduce survival rate. Here we tested this 'resonance fitness hypothesis' on the diurnal wasp Nasonia vitripennis, which exhibits a large latitudinal cline in free-running period with longer circadian period lengths in the north than in the south. Longevity was measured in northern and southern wasps placed into light-dark cycles (T-cycles) with periods ranging from 20 h to 28 h. Further, locomotor activity was recorded to estimate range and phase angle of entrainment under these various T-cycles. A light pulse induced phase response curve (PRC) was measured in both lines to understand entrainment results. We expected a concave survival curve with highest longevity at T = τ and a reduction in longevity the further τ deviates from T (τ/T<>1). Our results do not support this resonance fitness hypothesis. We did not observe a reduction in longevity when τ deviates from T. Our results may be understood by the strong circadian light resetting mechanism (type 0 PRC) to single light pulses that we measured in Nasonia, resulting in: (1) the broad range of entrainment, (2) the wide natural variation in circadian free-running period, and (3) the lack of reduced survival when τ/T ratio's deviates from 1. Together this indicates that circadian adaption to latitude may lead to changes in circadian period and light response, without negative influences on survival., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Pluronics P94 are block-copolymer showing prolonged circulation time and tumor-cell internalization in vitro, suggesting a potential for tumor accumulation and as a drug carrier. Here we report the results of the radiolabeled-P94 unimers (P94- 111 In-DTPA) on tumor uptake/retention and biodistribution after intravenous and intratumoral injection to tumor-bearing mice. Intravenous administration results in a high radioactive signal in the liver; while in tumor and other healthy tissues only low levels of radioactivity could be measured. In contrast, the intratumoral injection of P94 resulted in elevated levels of radioactivity in the tumor and low levels in other organs, including the liver. Independently from the injection route, the tumor tissue presented long retention of radioactivity. The minimal involvement of off-target tissues of P94, together with the excellent tracer retention over-time in the tumor designates Pluronic P94 copolymer as a highly promising carrier for anti-tumor drugs., (Copyright © 2017 Elsevier Inc. All rights reserved.)