Bayesian Networks for Max-linear Models

We study Bayesian networks based on max-linear structural equations as introduced in Gissibl and Kl\"uppelberg [16] and provide a summary of their independence properties. In particular we emphasize that distributions for such networks are generally not faithful to the independence model determined by their associated directed acyclic graph. In addition, we consider some of the basic issues of estimation and discuss generalized maximum likelihood estimation of the coefficients, using the concept of a generalized likelihood ratio for non-dominated families as introduced by Kiefer and Wolfowitz [21]. Finally we argue that the structure of a minimal network asymptotically can be identified completely from observational data.Comment: 18 page

Ecological resilience in lakes and the conjunction fallacy

There is a pressing need to apply stability and resilience theory to environmental management to restore degraded ecosystems effectively and to mitigate the effects of impending environmental change. Lakes represent excellent model case studies in this respect and have been used widely to demonstrate theories of ecological stability and resilience that are needed to underpin preventative management approaches. However, we argue that this approach is not yet fully developed because the pursuit of empirical evidence to underpin such theoretically grounded management continues in the absence of an objective probability framework. This has blurred the lines between intuitive logic (based on the elementary principles of probability) and extensional logic (based on assumption and belief) in this field

The Relationship between Fenestrations, Sieve Plates and Rafts in Liver Sinusoidal Endothelial Cells

Fenestrations are transcellular pores in endothelial cells that facilitate transfer of substrates between blood and the extravascular compartment. In order to understand the regulation and formation of fenestrations, the relationship between membrane rafts and fenestrations was investigated in liver sinusoidal endothelial cells where fenestrations are grouped into sieve plates. Three dimensional structured illumination microscopy, scanning electron microscopy, internal reflectance fluorescence microscopy and two-photon fluorescence microscopy were used to study liver sinusoidal endothelial cells isolated from mice. There was an inverse distribution between sieve plates and membrane rafts visualized by structured illumination microscopy and the fluorescent raft stain, Bodipy FL C5 ganglioside GM1. 7-ketocholesterol and/or cytochalasin D increased both fenestrations and lipid-disordered membrane, while Triton X-100 decreased both fenestrations and lipid-disordered membrane. The effects of cytochalasin D on fenestrations were abrogated by co-administration of Triton X-100, suggesting that actin disruption increases fenestrations by its effects on membrane rafts. Vascular endothelial growth factor (VEGF) depleted lipid-ordered membrane and increased fenestrations. The results are consistent with a sieve-raft interaction, where fenestrations form in non-raft lipid-disordered regions of endothelial cells once the membrane-stabilizing effects of actin cytoskeleton and membrane rafts are diminished.Full Tex

Алкогольные виртуальные реальности. Девиртуализация синдрома зависимости от алкоголя

Представлен новый взгляд на синдром зависимости от алкоголя с позиций виртуалистики как на параллельную виртуальную реальность. Подробно освещена рассматриваемая проблема, описан разработанный автором метод лечения алкоголизма ФорсажТМ и показана его высокая эффективность.A new idea about syndrome of alcohol addiction as a parallel virtual reality is presented. The problem is discussed in detail, the original method of treatment of alcoholism Forsazh(tm) is described, its high efficacy is shown

Chondroprotection by urocortin involves blockade of the mechanosensitive ion channel Piezo1

Osteoarthritis (OA) is characterised by progressive destruction of articular cartilage and chondrocyte cell death. Here, we show the expression of the endogenous peptide urocortin1 (Ucn1) and two receptor subtypes, CRF-R1 and CRF-R2, in primary human articular chondrocytes (AC) and demonstrate its role as an autocrine/paracrine pro-survival factor. This effect could only be removed using the CRF-R1 selective antagonist CP-154526, suggesting Ucn1 acts through CRF-R1 when promoting chondrocyte survival. This cell death was characterised by an increase in p53 expression, and cleavage of caspase 9 and 3. Antagonism of CRF-R1 with CP-154526 caused an accumulation of intracellular calcium (Ca2+) over time and cell death. These effects could be prevented with the non-selective cation channel blocker Gadolinium (Gd3+). Therefore, opening of a non-selective cation channel causes cell death and Ucn1 maintains this channel in a closed conformation. This channel was identified to be the mechanosensitive channel Piezo1. We go on to determine that this channel inhibition by Ucn1 is mediated initially by an increase in cyclic adenosine monophosphate (cAMP) and a subsequent inactivation of phospholipase A2 (PLA2), whose metabolites are known to modulate ion channels. Knowledge of these novel pathways may present opportunities for interventions that could abrogate the progression of OA

Mechanisms of T cell organotropism

F.M.M.-B. is supported by the British Heart Foundation, the Medical Research Council of the UK and the Gates Foundation

Morbidity related to defunctioning ileostomy closure after ileal pouch-anal anastomosis and low colonic anastomosis

Purpose Defunctioning ileostomies are widely performed in order to prevent or treat anastomotic leakage after colorectal surgery. The aim of the present study was to determine morbidity related to stoma closure and to identify predictive factors of a complicated postoperative course. Methods A consecutive series of 138 patients were retrospectively analyzed after stoma reversal. Data collection included general demographics and surgery-related aspects. Morbidity related to stoma closure was retrieved from our prospectively collected registry of complications. Results In 74 of 138 patients, defunctioning ileostomy was performed after restorative proctocolectomy and ileal pouchanal anastomosis (IPAA). The remaining ileostomies (n=64) were constructed after a low colorectal or coloanal anastomosis. A total of 46 complications were recorded in 28 patients resulting in an overall complication rate of 20.3%. Anastomotic leakage rate was 4.3%, and reoperation rate was 8.0%. The number of complications according to the Clavien-Dindo classification was 5 for grade I (10.9%), 26 for grade II (56.5%), 13 for grade III (28.3%), 1 for grade IV (2.2%), and 1 for grade V (2.2%). Multivariate analysis revealed a significantly higher ASA score in the complicated group (P=0.015, odds ratio 2.6, 95% confidence interval 1.2-5.6). Conclusions Closure of a defunctioning ileostomy is associated with 20% morbidity and a reoperation rate of 8%. There is an urgent need for criteria on which a more selective use of a defunctioning ileostomy after low colonic anastomosis or IPAA can be based given its associated morbidit

The case for open science: rare diseases.

The premise of Open Science is that research and medical management will progress faster if data and knowledge are openly shared. The value of Open Science is nowhere more important and appreciated than in the rare disease (RD) community. Research into RDs has been limited by insufficient patient data and resources, a paucity of trained disease experts, and lack of therapeutics, leading to long delays in diagnosis and treatment. These issues can be ameliorated by following the principles and practices of sharing that are intrinsic to Open Science. Here, we describe how the RD community has adopted the core pillars of Open Science, adding new initiatives to promote care and research for RD patients and, ultimately, for all of medicine. We also present recommendations that can advance Open Science more globally