To Belong or Not to Belong: Historical Reflections on Foreigners, Citizenship and Law

Even though ‘statelessness’ is a modern phenomenon that assumes the modern state and the modern states system, human history is abound with legal issues relating to people’s political and legal status, and with exclusion of and discrimination against outsiders. Since time immemorial, the political and legal status of people is crucial to the political and civil rights they have and can exercise, to their role in public affairs, to their legal standing, to access to courts and to determine what law applies to them. This paper addresses the issue of belonging, people’s legal and political status, citizenship and the treatment of foreigners from a legal historical perspective. It elaborates on these issues in ancient Greece and Rome, outlines the situation in medieval and early modern Europe and finally, goes into the rise of state citizenship as part of the emergence of the modern nation-state

MMP-2 and MMP-9 in normal mucosa are independently associated with outcome of colorectal cancer patients.

BackgroundUpregulation of the matrix metalloproteinases MMP-2 and MMP-9 in various cancers has been associated with worse survival of the patients.MethodsWe assessed MMP-2 and MMP-9 levels in normal colorectal mucosa from colorectal cancer patients in relation to the course of the disease.ResultsA high protein expression of MMP-2 as well as MMP-9 in normal mucosa was found to be correlated with worse 5-year survival. The combination of both parameters was an even stronger prognostic factor. These protein levels were found not to be related to the corresponding single nucleotide polymorphisms of MMP-2 (-1306C>T) and MMP-9 (-1562C>T). Multivariate analyses indicated that the MMP-2 and MMP-9 levels in normal mucosa are prognostic for survival, independent of TNM classification.ConclusionMMP-2 and MMP-9 levels in normal mucosa are indicative of the course of disease in colorectal cancer patients

MMP-2 geno-phenotype is prognostic for colorectal cancer survival, whereas MMP-9 is not.

The prognostic significance of single-nucleotide polymorphisms (SNPs) and tumour protein levels of MMP-2 and MMP-9 was evaluated in 215 colorectal cancer patients. Single-nucleotide polymorphism MMP-2(-1306T) and high MMP-2 levels were significantly associated with worse survival. Extreme tumour MMP-9 levels were associated with poor prognosis but SNP MMP-9(-1562C>T) was not. Tumour MMP levels were not determined by their SNP genotypes

Variability in subthalamic nucleus targeting for deep brain stimulation with 3 and 7 Tesla magnetic resonance imaging

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective surgical treatment for Parkinson's disease (PD). Side-effects may, however, be induced when the DBS lead is placed suboptimally. Currently, lower field magnetic resonance imaging (MRI) at 1.5 or 3 Tesla (T) is used for targeting. Ultra-high-field MRI (7 T and above) can obtain superior anatomical information and might therefore be better suited for targeting. This study aims to test whether optimized 7 T imaging protocols result in less variable targeting of the STN for DBS compared to clinically utilized 3 T images. Three DBS-experienced neurosurgeons determined the optimal STN DBS target site on three repetitions of 3 T-T2, 7 T-T2*, 7 T-R2* and 7 T-QSM images for five PD patients. The distance in millimetres between the three repetitive coordinates was used as an index of targeting variability and was compared between field strength, MRI contrast and repetition with a Bayesian ANOVA. Further, the target coordinates were registered to MNI space, and anatomical coordinates were compared between field strength, MRI contrast and repetition using a Bayesian ANOVA. The results indicate that the neurosurgeons are stable in selecting the DBS target site across MRI field strength, MRI contrast and repetitions. The analysis of the coordinates in MNI space however revealed that the actual selected location of the electrode is seemingly more ventral when using the 3 T scan compared to the 7 T scans

Synthesizing Speech from Intracranial Depth Electrodes using an Encoder-Decoder Framework

Speech Neuroprostheses have the potential to enable communication for people with dysarthria or anarthria. Recent advances have demonstrated high-quality text decoding and speech synthesis from electrocorticographic grids placed on the cortical surface. Here, we investigate a less invasive measurement modality in three participants, namely stereotactic EEG (sEEG) that provides sparse sampling from multiple brain regions, including subcortical regions. To evaluate whether sEEG can also be used to synthesize high-quality audio from neural recordings, we employ a recurrent encoder-decoder model based on modern deep learning methods. We find that speech can indeed be reconstructed with correlations up to 0.8 from these minimally invasive recordings, despite limited amounts of training data

Tissue levels of matrix metalloproteinases MMP-2 and MMP-9 are related to the overall survival of patients with gastric carcinoma.

Proteinases are involved in tumour invasion and metastasis. Several matrix metalloproteinases (MMPs) have been shown to be increased in various human carcinomas. We assessed the levels of MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in 50 gastric carcinomas and corresponding mucosa using quantitative gelatin zymography. Both MMP levels were significantly enhanced in gastric carcinomas compared with adjacent mucosal tissue, showed a relatively poor intercorrelation and no relation was found with histopathological carcinoma classifications according to Laurén, WHO and tumour-node-metastasis (TNM). Cox's multivariate proportional hazards analyses revealed that high carcinomatous MMP values are of prognostic significance for a poor overall survival of the patients, independent of the major clinicopathological parameters

Implementation of a mobile 0.15-T intraoperative MR system in pediatric neuro-oncological surgery: feasibility and correlation with early postoperative high-field strength MRI

INTRODUCTION: We analyze our preliminary experience using the PoleStar N20 mobile intraoperative MR (iMR) system as an adjunct for pediatric brain tumor resection. METHODS: We analyzed 11 resections in nine children between 1 month and 17 years old. After resection, we acquired iMR scans to detect residual tumor and update neuronavigation. We compared final iMR interpretation by the neurosurgeon with early postoperative MR interpretation by a neuroradiologist. RESULTS: Patient positioning was straightforward, and image quality (T1 7-min 4-mm sequences) sufficient in all cases. In five cases, contrast enhancement suspect for residual tumor was noted on initial postresection iMR images. In one case, a slight discrepancy with postoperative imaging after 3 months was no longer visible after 1 year. No serious perioperative adverse events related to the PoleStar N20 were encountered, except for transient shoulder pain in two. CONCLUSIONS: Using the PoleStar N20 iMR system is technically feasible and safe for both supra- and infratentorial tumor resections in children of all ages. Their small head and shoulders favor positioning in the magnet bore and allow the field of view to cover more than the area of primary interest, e.g., the ventricles in an infratentorial case. Standard surgical equipment may be used without significant limitations. In this series, the use of iMR leads to an increased extent of tumor resection in 45 % of cases. Correlation between iMR and early postoperative MR is excellent, provided image quality is optimal and interpretation is carefully done by someone sufficiently familiar with the system

RefCell: multi-dimensional analysis of image-based high-throughput screens based on ‘typical cells’

Image-based high-throughput screening (HTS) reveals a high level of heterogeneity in single cells and multiple cellular states may be observed within a single population. Currently available high-dimensional analysis methods are successful in characterizing cellular heterogeneity, but suffer from the “curse of dimensionality” and non-standardized outputs. Here we introduce RefCell, a multi-dimensional analysis pipeline for image-based HTS that reproducibly captures cells with typical combinations of features in reference states and uses these “typical cells” as a reference for classification and weighting of metrics. RefCell quantitatively assesses heterogeneous deviations from typical behavior for each analyzed perturbation or sample. We apply RefCell to the analysis of data from a high-throughput imaging screen of a library of 320 ubiquitin-targeted siRNAs selected to gain insights into the mechanisms of premature aging (progeria). RefCell yields results comparable to a more complex clustering-based single-cell analysis method; both methods reveal more potential hits than a conventional analysis based on averages.https://doi.org/10.1186/s12859-018-2454-