Migraine-Associated Common Genetic Variants Confer Greater Risk of Posterior vs. Anterior Circulation Ischemic Stroke☆.

OBJECTIVE: To examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects. METHODS: Acute ischemic stroke cases were classified as PCiS or ACiS based on lesion location on diffusion-weighted MRI. Exclusion criteria were lesions in both vascular territories or uncertain territory; supratentorial PCiS with ipsilateral fetal posterior cerebral artery; and cases with atrial fibrillation. We generated migraine PRS for three migraine phenotypes (any migraine; migraine without aura; migraine with aura) using publicly available GWAS data and compared mean PRSs separately for PCiS and ACiS vs. non-stroke control subjects, and between each stroke phenotype. RESULTS: Our primary analyses included 464 PCiS and 1079 ACiS patients with genetic European ancestry. Compared to non-stroke control subjects (n=15396), PRSs of any migraine were associated with increased risk of PCiS (p=0.01-0.03) and decreased risk of ACiS (p=0.010-0.039). Migraine without aura PRSs were significantly associated with PCiS (p=0.008-0.028), but not with ACiS. When comparing PCiS vs. ACiS directly, migraine PRSs were higher in PCiS vs. ACiS for any migraine (p=0.001-0.010) and migraine without aura (p=0.032-0.048). Migraine with aura PRS did not show a differential association in our analyses. CONCLUSIONS: Our results suggest a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function.

[Validation of the German translation of the ASAS health index : A questionnaire to assess functioning and health in patients with spondyloarthritis]. / Validierung der deutschen Version des ASAS-Gesundheitsindex : Ein Fragebogen zur Erfassung von Funktionsfähigkeit und Gesundheit bei Patienten mit Spondyloarthritis.

INTRODUCTION: The aim of this study was the validation of the German translation of the ASAS Health Index (ASAS HI), which measures functioning and health in patients with axial and peripheral spondyloarthritis (SpA). METHOD: Patients with SpA who fulfilled the ASAS classification criteria for axial (axSpA) or peripheral SpA (pSpA) were included in this study. Constuct validity of the ASAS HI was tested by using Spearman's correlation coefficients. Reliability was analyzed by intraclass correlation coefficients (ICC) in patients with stable disease. In patients requiring an important therapeutic change because of unacceptable high disease activity, the sensitivity to change was analyzed using standardized response mean (SRM). RESULTS: A total of 171 patients (57.9% male, age 44.4 ± 13.0 years) were included. The internal consistency was high with a Cronbach's alpha of 0.83. The reliability (n = 63) was good (ICC = 0.94; 95% confidence interval [CI] 0.90-0.96). The sensitivity to change of the ASAS HI was low for a relatively small number of cases (n = 33) with a SRM of -0.27 but showed a good ability to discriminate between various stages of disease activity and physical functioning. DISCUSSION: We showed that the German translation of the ASAS HI provide good psychometric properties to assess functioning and health in patients with SpA. This reliable and sensitive to change questionnaire therefore enables the assessment of disease-specific global functioning and severity in patients with all forms of SpA.

Assessing Restoration Effects on River Hydromorphology Using the Process-based Morphological Quality Index in Eight European River Reaches.

The Morphological Quality Index (MQI) and the Morphological Quality Index for monitoring (MQIm) have been applied to eight case studies across Europe with the objective of analyzing the hydromorphological response to various restoration measures and of comparing the results of the MQI and MQIm as a morphological assessment applied at the reach scale, with a conventional site scale physical-habitat assessment method. For each restored reach, the two indices were applied to the pre-restoration and post-restoration conditions. The restored reach was also compared to an adjacent, degraded reach. Results show that in all cases the restoration measures improved the morphological quality of the reach, but that the degree of improvement depends on many factors, including the initial morphological conditions, the length of the restored portion in relation to the reach length, and on the type of intervention. The comparison with a conventional site scale physical-habitat assessment method shows that the MQI and MQIm are best suited for the evaluation of restoration effects on river hydromorphology at the geomorphologically-relevant scale of the river reach.

Characterising brain network topologies: A dynamic analysis approach using heat kernels.

Network theory provides a principled abstraction of the human brain: reducing a complex system into a simpler representation from which to investigate brain organisation. Recent advancement in the neuroimaging field is towards representing brain connectivity as a dynamic process in order to gain a deeper understanding of how the brain is organised for information transport. In this paper we propose a network modelling approach based on the heat kernel to capture the process of heat diffusion in complex networks. By applying the heat kernel to structural brain networks, we define new features which quantify change in heat propagation. Identifying suitable features which can classify networks between cohorts is useful towards understanding the effect of disease on brain architecture. We demonstrate the discriminative power of heat kernel features in both synthetic and clinical preterm data. By generating an extensive range of synthetic networks with varying density and randomisation, we investigate heat diffusion in relation to changes in network topology. We demonstrate that our proposed features provide a metric of network efficiency and may be indicative of organisational principles commonly associated with, for example, small-world architecture. In addition, we show the potential of these features to characterise and classify between network topologies. We further demonstrate our methodology in a clinical setting by applying it to a large cohort of preterm babies scanned at term equivalent age from which diffusion networks were computed. We show that our heat kernel features are able to successfully predict motor function measured at two years of age (sensitivity, specificity, F-score, accuracy = 75.0, 82.5, 78.6, and 82.3%, respectively).

[German translation and cross-cultural adaptation of the ASAS health index : An ICF-based instrument for documentation of functional ability in patients with ankylosing spondylitis]. / Deutsche Übersetzung und krosskulturelle Adaptation des ASAS-Gesundheitsindex : Ein ICF-basiertes Instrument zur Erfassung der Funktionsfähigkeit von Patienten mit ankylosierender Spondylitis.

Documentation of the severity of the disease in patients with spondyloarthritis (SpA) can represent a clinical challenge, especially as the course of SpA can be very different. Patients with SpA often complain of symptoms, such as pain, fatigue and stiffness as well as limitations in mental functions and social participation. This wide range of functional impairments could so far only be insufficiently documented and not with one single measurement instrument. Despite various attempts in recent years, experts could not reach agreement on a definition of the severity and documentation of the extent of the severity. This was the starting point for the development of the ASAS health index presented here, which initially focused on patients with ankylosing spondylitis (AS). This questionnaire serves to document the health and functional ability of patients with AS and has been available since 2015 as the original english version of the ASAS health index together with the accompanying environmental factors set. This article describes the German translation and transcultural adaptation of the ASAS health index and the accompanying environmental factors set.

Raman spectroscopy for postmortem interval estimation of human skeletal remains: A scoping review.

Estimating postmortem intervals (PMI) is crucial in forensic investigations, providing insights into criminal cases and determining the time of death. PMI estimation relies on expert experience and a combination of thanatological data and environmental factors but is prone to errors. The lack of reliable methods for assessing PMI in bones and soft tissues necessitates a better understanding of bone decomposition. Several research groups have shown promise in PMI estimation in skeletal remains but lack valid data for forensic cases. Current methods are costly, time-consuming, and unreliable for PMIs over 5 years. Raman spectroscopy (RS) can potentially estimate PMI by studying chemical modifications in bones and teeth correlated with burial time. This review summarizes RS applications, highlighting its potential as an innovative, nondestructive, and fast technique for PMI estimation in forensic medicine.

Moving targets, long-lived infrastructure, and increasing needs for integration and adaptation in water management: an illustration from Switzerland.

Switzerland provides an example of successful management of water infrastructure and water resources that was accomplished largely without integration across sectors. Limitations in this approach have become apparent; decisions that were formerly based only on technical and economic feasibility must now incorporate broader objectives such as ecological impact. In addition, current and emerging challenges relate to increasingly complex problems that are likely to demand more integrated approaches. If such integration is to be of benefit, it must be possible to redirect resources across sectors, and the synergies derived from integration must outweigh the additional cost of increased complexity.

[Expectations of rheumatologists on imaging results]. / Erwartungen des Rheumatologen an die Bildgebung.

CLINICAL/METHODICAL ISSUE: Clinical examination and laboratory results are often insufficient to support therapeutic decisions. STANDARD RADIOLOGICAL METHODS: Diagnosis and organ-related imaging may provide important additional information for initial diagnosis (differential diagnoses), follow-up and prognosis. Especially functional imaging techniques, such as ultrasound and magnetic resonance imaging are becoming more and more important for early diagnosis. METHODICAL INNOVATIONS: Imaging is already recognized in the classification criteria of several rheumatic diseases and new criteria for spondyloarthritis and polymyalgia rheumatica aim more and more at early diagnosis using functional imaging techniques, such as ultrasound and magnetic resonance imaging. PERFORMANCE: Specific imaging findings are helpful for eliminating differential diagnoses. During follow-up disease control the status as well as progression of structural damage can be documented. In selected diseases imaging allows prognostic statements on both disease progression and therapeutic response to specific medication. ACHIEVEMENTS: The evidential value of imaging results varies with the rheumatological expectations. PRACTICAL RECOMMENDATIONS: Overall rheumatological expectations on imaging differ widely and therefore support a differentiated use of imaging techniques.

[Giant-cell arteritis: update: diagnosis and therapy]. / Riesenzellarteritis : Update: Diagnose und Therapie.

Giant-cell arteritis (GCA) is the most common form of vasculitis in patients over 50 years old. Loss of vision is the most common severe complication but involvement of extracranial arteries including the aorta is more frequent than previously assumed. The role of dendritic and T-cells indicates the presence of an antibody but a clear association with underlying infections has not yet been demonstrated. Even if the inflammation parameters in blood are mostly increased in the diagnosis of GCA, specific laboratory tests for the diagnosis of GCA are not available. Of the imaging procedures ultrasonography, magnetic resonance imaging and (18)F-fluorodeoxyglucose positron emission tomography can be useful to localize and estimate the extent of vascular involvement. Glucocorticoids are still the standard therapy of GCA, whereby the cumulative dose can possibly be reduced by additional methotrexate. In addition acetylsalicylic acid is recommended as prophylaxis against cardiovascular and cerebrovascular events as well as prophylaxis and therapy of accompanying osteoporosis.

Electron-beam-induced deposition and post-treatment processes to locally generate clean titanium oxide nanostructures on Si(100).

We have investigated the lithographic generation of TiO(x) nanostructures on Si(100) via electron-beam-induced deposition (EBID) of titanium tetraisopropoxide (TTIP) in ultra-high vacuum (UHV) by scanning electron microscopy (SEM) and local Auger electron spectroscopy (AES). In addition, the fabricated nanostructures were also characterized ex situ via atomic force microscopy (AFM) under ambient conditions. In EBID, a highly focused electron beam is used to locally decompose precursor molecules and thereby to generate a deposit. A drawback of this nanofabrication technique is the unintended deposition of material in the vicinity of the impact position of the primary electron beam due to so-called proximity effects. Herein, we present a post-treatment procedure to deplete the unintended deposits by moderate sputtering after the deposition process. Moreover, we were able to observe the formation of pure titanium oxide nanocrystals (<100 nm) in situ upon heating the sample in a well-defined oxygen atmosphere. While the nanocrystal growth for the as-deposited structures also occurs in the surroundings of the irradiated area due to proximity effects, it is limited to the pre-defined regions, if the sample was sputtered before heating the sample under oxygen atmosphere. The described two-step post-treatment procedure after EBID presents a new pathway for the fabrication of clean localized nanostructures.

Fabrication of layered nanostructures by successive electron beam induced deposition with two precursors: protective capping of metallic iron structures.

We report on the stepwise generation of layered nanostructures via electron beam induced deposition (EBID) using organometallic precursor molecules in ultra-high vacuum (UHV). In a first step a metallic iron line structure was produced using iron pentacarbonyl; in a second step this nanostructure was then locally capped with a 2-3 nm thin titanium oxide-containing film fabricated from titanium tetraisopropoxide. The chemical composition of the deposited layers was analyzed by spatially resolved Auger electron spectroscopy. With spatially resolved x-ray absorption spectroscopy at the Fe L3 edge, it was demonstrated that the thin capping layer prevents the iron structure from oxidation upon exposure to air.

Monocarboxylate transporter-1 (MCT1) protein expression in head and neck cancer affects clinical outcome.

Treatment of locally advanced, unresectable head and neck squamous cell carcinoma (HNSCC) often yields only modest results with radiochemotherapy (RCT) as standard of care. Prognostic features related to outcome upon RCT might be highly valuable to improve treatment. Monocarboxylate transporters-1 and -4 (MCT1/MCT4) were evaluated as potential biomarkers. A cohort of HNSCC patients without signs for distant metastases was assessed eliciting 82 individuals eligible whereof 90% were diagnosed with locally advanced stage IV. Tumor specimens were stained for MCT1 and MCT4 in the cell membrane by immunohistochemistry. Obtained data were evaluated with respect to overall (OS) and progression-free survival (PFS). Protein expression of MCT1 and MCT4 in cell membrane was detected in 16% and 85% of the tumors, respectively. Expression of both transporters was not statistically different according to the human papilloma virus (HPV) status. Positive staining for MCT1 (n = 13, negative in n = 69) strongly worsened PFS with a hazard ratio (HR) of 3.1 (95%-confidence interval 1.6-5.7, p < 0.001). OS was likewise affected with a HR of 3.8 (2.0-7.3, p < 0.001). Multivariable Cox regression confirmed these findings. We propose MCT1 as a promising biomarker in HNSCC treated by primary RCT.

Peak Width of Skeletonized Mean Diffusivity as Neuroimaging Biomarker in Cerebral Amyloid Angiopathy.

BACKGROUND AND PURPOSE: Whole-brain network connectivity has been shown to be a useful biomarker of cerebral amyloid angiopathy and related cognitive impairment. We evaluated an automated DTI-based method, peak width of skeletonized mean diffusivity, in cerebral amyloid angiopathy, together with its association with conventional MRI markers and cognitive functions. MATERIALS AND METHODS: We included 24 subjects (mean age, 74.7 [SD, 6.0] years) with probable cerebral amyloid angiopathy and mild cognitive impairment and 62 patients with MCI not attributable to cerebral amyloid angiopathy (non-cerebral amyloid angiopathy-mild cognitive impairment). We compared peak width of skeletonized mean diffusivity between subjects with cerebral amyloid angiopathy-mild cognitive impairment and non-cerebral amyloid angiopathy-mild cognitive impairment and explored its associations with cognitive functions and conventional markers of cerebral small-vessel disease, using linear regression models. RESULTS: Subjects with Cerebral amyloid angiopathy-mild cognitive impairment showed increased peak width of skeletonized mean diffusivity in comparison to those with non-cerebral amyloid angiopathy-mild cognitive impairment (P < .001). Peak width of skeletonized mean diffusivity values were correlated with the volume of white matter hyperintensities in both groups. Higher peak width of skeletonized mean diffusivity was associated with worse performance in processing speed among patients with cerebral amyloid angiopathy, after adjusting for other MRI markers of cerebral small vessel disease. The peak width of skeletonized mean diffusivity did not correlate with cognitive functions among those with non-cerebral amyloid angiopathy-mild cognitive impairment. CONCLUSIONS: Peak width of skeletonized mean diffusivity is altered in cerebral amyloid angiopathy and is associated with performance in processing speed. This DTI-based method may reflect the degree of white matter structural disruption in cerebral amyloid angiopathy and could be a useful biomarker for cognition in this population.

Evaluation of xenobiotic impact on urban receiving waters by means of statistical methods.

Xenobiotics in urban receiving waters are an emerging problem. A sound knowledge of xenobiotic input, distribution and fate in the aquatic environment is a prerequisite for risk assessments. Methods to assess the impact of xenobiotics on urban receiving waters should address the diverse characteristics of the target compounds and the spatiotemporal variability of concentrations. Here, we present results from a one-year-monitoring program concerning concentrations of pharmaceuticals, additives from personal care products and industrial chemicals in an urban drainage catchment in untreated and treated wastewater, surface water and groundwater. Univariate and multivariate statistical methods were applied to characterize the xenobiotic concentrations. Correlation and principal component analysis revealed a pronounced pattern of xenobiotics in the surface water samples. The concentrations of several xenobiotics were characterized by a negative proportionality to the water temperature. Therefore, seasonal attenuation is assumed to be a major process influencing the measured concentrations. Moreover, dilution of xenobiotics the surface water was found to significantly influence the concentrations. These two processes control more the xenobiotic occurrence in the surface water than the less pronounced concentration pattern in the wastewater sources. For the groundwater samples, we assume that foremost attenuation processes lead to the found differentiation of xenobiotics.

Ligamentum flavum cyst in the lumbar spine: a case report and review of the literature.

Degenerative changes in the lumbar spine can be followed by cystic changes. Most reported intraspinal cysts are ganglion or synovial cysts. Ligamentum flavum pseudocyst, as a cystic lesion in the lumbar spine, is a rare and unusual cause of neurologic signs and symptoms and is usually seen in elderly persons (due to degenerative changes). They are preferentially located in the lower lumbar region, while cervical localization is rare. Complete removal of the cyst leads to excellent results and seems to preclude recurrence. We report the case of a right-sided ligamentum flavum cyst occurring at L3-L4 level in a 70-year-old woman, which was surgically removed with excellent postoperative results and complete resolution of symptoms. In addition, we discuss and review reports in the literature.

The future of pathology is digital.

Information, archives, and intelligent artificial systems are part of everyday life in modern medicine. They already support medical staff by mapping their workflows with shared availability of cases' referral information, as needed for example, by the pathologist, and this support will be increased in the future even more. In radiology, established standards define information models, data transmission mechanisms, and workflows. Other disciplines, such as pathology, cardiology, and radiation therapy, now define further demands in addition to these established standards. Pathology may have the highest technical demands on the systems, with very complex workflows, and the digitization of slides generating enormous amounts of data up to Gigabytes per biopsy. This requires enormous amounts of data to be generated per biopsy, up to the gigabyte range. Digital pathology allows a change from classical histopathological diagnosis with microscopes and glass slides to virtual microscopy on the computer, with multiple tools using artificial intelligence and machine learning to support pathologists in their future work.

Comparison of structure and composition of a fossil Champsosaurus vertebra with modern Crocodylidae vertebrae: A multi-instrumental approach.

Information on the adaptation of bone structures during evolution is rare since histological data are limited. Micro- and nano-computed tomography of a fossilized vertebra from Champsosaurus sp., which has an estimated age of 70-73 million years, revealed lower porosity and higher bone density compared to modern Crocodylidae vertebrae. Mid-infrared reflectance and energy dispersive X-ray mapping excluded a petrification process, and demonstrated a typical carbonate apatite distribution, confirming histology in light- and electron microscopy of the preserved vertebra. As a consequence of this evolutionary process, the two vertebrae of modern Crocodylidae show reduced overall stiffness in the finite element analysis simulation compared to the fossilized Champsosaurus sp. vertebra, with predominant stiffness along the longitudinal z-axes.

Detailed phenotyping of posterior vs. anterior circulation ischemic stroke: a multi-center MRI study.

OBJECTIVE: Posterior circulation ischemic stroke (PCiS) constitutes 20-30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes in PCiS vs. ACiS and lesion location on magnetic resonance imaging (MRI) in PCiS. METHODS: Out of 3,301 MRIs from 12 sites in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN), we included 2,381 cases with acute DWI lesions. The definition of ACiS or PCiS was based on lesion location. We compared the groups using Chi-squared and logistic regression. RESULTS: PCiS occurred in 718 (30%) patients and ACiS in 1663 (70%). Diabetes and male sex were more common in PCiS vs. ACiS (diabetes 27% vs. 23%, p < 0.05; male sex 68% vs. 58%, p < 0.001). Both were independently associated with PCiS (diabetes, OR = 1.29; 95% CI 1.04-1.61; male sex, OR = 1.46; 95% CI 1.21-1.78). ACiS more commonly had large artery atherosclerosis (25% vs. 20%, p < 0.01) and cardioembolic mechanisms (17% vs. 11%, p < 0.001) compared to PCiS. Small artery occlusion was more common in PCiS vs. ACiS (20% vs. 14%, p < 0.001). Small artery occlusion accounted for 47% of solitary brainstem infarctions. CONCLUSION: Ischemic stroke subtypes differ between the two phenotypes. Diabetes and male sex have a stronger association with PCiS than ACiS. Definitive MRI-based PCiS diagnosis aids etiological investigation and contributes additional insights into specific risk factors and mechanisms of injury in PCiS.