EU Referendums in Context: What can we learn from the Swiss Case?

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordThe rising number of referendums on EU matters, such as the Brexit and the Catalonian independence votes, highlight the increasing importance of referendums as a problem‐solving mechanism in the EU. We argue that the Swiss case provides essential insights into understanding the dynamics behind referendums, which are often lacking when referendums are called for in the EU. Referendums in EU member states on EU matters differ substantially from the in Swiss context. Nevertheless, proponents of more direct democratic decision‐making regularly cite the Swiss example. Our systematic analysis of why referendums are called, how they unfold and their resulting effects in the EU and Switzerland reveals that the EU polity lacks the crucial conditions that embed direct democracy within the wider political and institutional system. The comparative perspective offers fundamental insights into the pre‐conditions required for direct democracy to function and its limitations in the EU

Evaluation of Load-To-Strength Ratios in Metastatic Vertebrae and Comparison With Age- and Sex-Matched Healthy Individuals.

Vertebrae containing osteolytic and osteosclerotic bone metastases undergo pathologic vertebral fracture (PVF) when the lesioned vertebrae fail to carry daily loads. We hypothesize that task-specific spinal loading patterns amplify the risk of PVF, with a higher degree of risk in osteolytic than in osteosclerotic vertebrae. To test this hypothesis, we obtained clinical CT images of 11 cadaveric spines with bone metastases, estimated the individual vertebral strength from the CT data, and created spine-specific musculoskeletal models from the CT data. We established a musculoskeletal model for each spine to compute vertebral loading for natural standing, natural standing + weights, forward flexion + weights, and lateral bending + weights and derived the individual vertebral load-to-strength ratio (LSR). For each activity, we compared the metastatic spines' predicted LSRs with the normative LSRs generated from a population-based sample of 250 men and women of comparable ages. Bone metastases classification significantly affected the CT-estimated vertebral strength (Kruskal-Wallis, p < 0.0001). Post-test analysis showed that the estimated vertebral strength of osteosclerotic and mixed metastases vertebrae was significantly higher than that of osteolytic vertebrae (p = 0.0016 and p = 0.0003) or vertebrae without radiographic evidence of bone metastasis (p = 0.0010 and p = 0.0003). Compared with the median (50%) LSRs of the normative dataset, osteolytic vertebrae had higher median (50%) LSRs under natural standing (p = 0.0375), natural standing + weights (p = 0.0118), and lateral bending + weights (p = 0.0111). Surprisingly, vertebrae showing minimal radiographic evidence of bone metastasis presented significantly higher median (50%) LSRs under natural standing (p < 0.0001) and lateral bending + weights (p = 0.0009) than the normative dataset. Osteosclerotic vertebrae had lower median (50%) LSRs under natural standing (p < 0.0001), natural standing + weights (p = 0.0005), forward flexion + weights (p < 0.0001), and lateral bending + weights (p = 0.0002), a trend shared by vertebrae with mixed lesions. This study is the first to apply musculoskeletal modeling to estimate individual vertebral loading in pathologic spines and highlights the role of task-specific loading in augmenting PVF risk associated with specific bone metastatic types. Our finding of high LSRs in vertebrae without radiologically observed bone metastasis highlights that patients with metastatic spine disease could be at an increased risk of vertebral fractures even at levels where lesions have not been identified radiologically

Alignment of cellular motility forces with tissue flow as a mechanism for efficient wound healing

Recent experiments have shown that spreading epithelial sheets exhibit a long-range coordination of motility forces that leads to a buildup of tension in the tissue, which may enhance cell division and the speed of wound healing. Furthermore, the edges of these epithelial sheets commonly show finger-like protrusions whereas the bulk often displays spontaneous swirls of motile cells. To explain these experimental observations, we propose a simple flocking-type mechanism, in which cells tend to align their motility forceswith their velocity. Implementing this idea in amechanical tissue simulation, the proposed model gives rise to efficient spreading and can explain the experimentally observed long-range alignment of motility forces in highly disordered patterns, as well as the buildup of tensile stress throughout the tissue. Our model also qualitatively reproduces the dependence of swirl size and swirl velocity on cell density reported in experiments and exhibits an undulation instability at the edge of the spreading tissue commonly observed in vivo. Finally, we study the dependence of colony spreading speed on important physical and biological parameters and derive simple scaling relations that show that coordination of motility forces leads to an improvement of the wound healing process for realistic tissue parameters

Design patterns for resource-constrained automated deep-learning methods

We present an extensive evaluation of a wide variety of promising design patterns for automated deep-learning (AutoDL) methods, organized according to the problem categories of the 2019 AutoDL challenges, which set the task of optimizing both model accuracy and search efficiency under tight time and computing constraints. We propose structured empirical evaluations as the most promising avenue to obtain design principles for deep-learning systems due to the absence of strong theoretical support. From these evaluations, we distill relevant patterns which give rise to neural network design recommendations. In particular, we establish (a) that very wide fully connected layers learn meaningful features faster; we illustrate (b) how the lack of pretraining in audio processing can be compensated by architecture search; we show (c) that in text processing deep-learning-based methods only pull ahead of traditional methods for short text lengths with less than a thousand characters under tight resource limitations; and lastly we present (d) evidence that in very data- and computing-constrained settings, hyperparameter tuning of more traditional machine-learning methods outperforms deep-learning systems

The Origins of Concentric Demyelination: Self-Organization in the Human Brain

Baló's concentric sclerosis is a rare atypical form of multiple sclerosis characterized by striking concentric demyelination patterns. We propose a robust mathematical model for Baló's sclerosis, sharing common molecular and cellular mechanisms with multiple sclerosis. A reconsideration of the analogies between Baló's sclerosis and the Liesegang periodic precipitation phenomenon led us to propose a chemotactic cellular model for this disease. Rings of demyelination appear as a result of self-organization processes, and closely mimic Baló lesions. According to our results, homogeneous and concentric demyelinations may be two different macroscopic outcomes of a single fundamental immune disorder. Furthermore, in chemotactic models, cellular aggressivity appears to play a central role in pattern formation

Femoral nerve compression secondary to a ganglion cyst arising from a hip joint: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Femoral nerve compression due to a cystic lesion around the hip joint is rare and only a few cases have been described in the literature. Among these, true ganglion cysts are even more rare.</p> <p>Case presentation</p> <p>We report the case of a 57-year-old woman with femoral nerve compression caused by a true ganglion cyst of the hip joint.</p> <p>Conclusion</p> <p>A high index of suspicion is required to predict a non-palpable cystic lesion around the hip joint as it may mimic different disorders and should be kept in mind in the differential diagnosis of unusual groin pain, radicular pain and peripheral vascular disorders.</p

Changing climate and outbreaks of forest pest insects in a cold northern country, Finland

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Inhibition of SLPI ameliorates disease activity in experimental autoimmune encephalomyelitis

<p>Abstract</p> <p>Background</p> <p>The secretory leukocyte protease inhibitor (SLPI) exerts wide ranging effects on inflammatory pathways and is upregulated in EAE but the biological role of SLPI in EAE, an animal model of multiple sclerosis is unknown</p> <p>Methods</p> <p>To investigate the pathophysiological effects of SLPI within EAE, we induced SLPI-neutralizing antibodies in mice and rats to determine the clinical severity of the disease. In addition we studied the effects of SLPI on the anti-inflammatory cytokine TGF-β.</p> <p>Results</p> <p>The induction of SLPI neutralizing antibodies resulted in a milder disease course in mouse and rat EAE. SLPI neutralization was associated with increased serum levels of TGF-β and increased numbers of FoxP3+ CD4+ T cells in lymph nodes. <it>In vitro</it>, the addition of SLPI significantly decreased the number of functional FoxP3+ CD25^hiCD4+ regulatory T cells in cultures of naive human CD4+ T cells. Adding recombinant TGF-β to SLPI-treated human T cell cultures neutralized SLPI's inhibitory effect on regulatory T cell differentiation.</p> <p>Conclusion</p> <p>In EAE, SLPI exerts potent pro-inflammatory actions by modulation of T-cell activity and its neutralization may be beneficial for the disease.</p