GridNet with automatic shape prior registration for automatic MRI cardiac segmentation

In this paper, we propose a fully automatic MRI cardiac segmentation method based on a novel deep convolutional neural network (CNN) designed for the 2017 ACDC MICCAI challenge. The novelty of our network comes with its embedded shape prior and its loss function tailored to the cardiac anatomy. Our model includes a cardiac centerof-mass regression module which allows for an automatic shape prior registration. Also, since our method processes raw MR images without any manual preprocessing and/or image cropping, our CNN learns both high-level features (useful to distinguish the heart from other organs with a similar shape) and low-level features (useful to get accurate segmentation results). Those features are learned with a multi-resolution conv-deconv "grid" architecture which can be seen as an extension of the U-Net. Experimental results reveal that our method can segment the left and right ventricles as well as the myocardium from a 3D MRI cardiac volume in 0.4 second with an average Dice coefficient of 0.90 and an average Hausdorff distance of 10.4 mm.Comment: 8 pages, 1 tables, 2 figure

Measuring the performance of investments in information security startups: An empirical analysis by cybersecurity sectors using Crunchbase data

Early-stage firms play a significant role in driving innovation and creating new products and services, especially for cybersecurity. Therefore, evaluating their performance is crucial for investors and policymakers. This work presents a financial evaluation of early-stage firms' performance in 19 cybersecurity sectors using a private-equity dataset from 2010 to 2022 retrieved from Crunchbase. We observe firms, their primary and secondary activities, funding rounds, and pre and post-money valuations. We compare cybersecurity sectors regarding the amount raised over funding rounds and post-money valuations while inferring missing observations. We observe significant investor interest variations across categories, periods, and locations. In particular, we find the average capital raised (valuations) to range from USD 7.24 mln (USD 32.39 mln) for spam filtering to USD 45.46 mln (USD 447.22 mln) for the private cloud sector. Next, we assume a log process for returns computed from post-money valuations and estimate the expected returns, systematic and specific risks, and risk-adjusted returns of investments in early-stage firms belonging to cybersecurity sectors. Again, we observe substantial performance variations with annualized expected returns ranging from 9.72\% for privacy to 177.27\% for the blockchain sector. Finally, we show that overall, the cybersecurity industry performance is on par with previous results found in private equity. Our results shed light on the performance of cybersecurity investments and, thus, on investors' expectations about cybersecurity.Comment: This document results from a research project funded by the Cyber-Defence Campus, armasuisse Science and Technology. We appreciate helpful comments from seminar participants at the Cyber Alp Retreat 2022 and WEIS 202

Prioritizing Investments in Cybersecurity: Empirical Evidence from an Event Study on the Determinants of Cyberattack Costs

Along with the increasing frequency and severity of cyber incidents, understanding their economic implications is paramount. In this context, listed firms' reactions to cyber incidents are compelling to study since they (i) are a good proxy to estimate the costs borne by other organizations, (ii) have a critical position in the economy, and (iii) have their financial information publicly available. We extract listed firms' cyber incident dates and characteristics from newswire headlines. We use an event study over 2012--2022, using a three-day window around events and standard benchmarks. We find that the magnitude of abnormal returns around cyber incidents is on par with previous studies using newswire or alternative data to identify cyber incidents. Conversely, as we adjust the standard errors accounting for event-induced variance and residual cross-correlation, we find that the previously claimed significance of abnormal returns vanishes. Given these results, we run a horse race of specifications, in which we test for the marginal effects of type of cyber incidents, target firm sector, periods, and their interactions. Data breaches are the most detrimental incident type with an average loss of -1.3\% or (USD -1.9 billion) over the last decade. The health sector is the most sensitive to cyber incidents, with an average loss of -5.21\% (or USD -1.2 billion), and even more so when these are data breaches. Instead, we cannot show any time-varying effect of cyber incidents or a specific effect of the type of news as had previously been advocated.Comment: This document results from a research project funded by the Cyber-Defence Campus, armasuisse Science and Technology. Our code will be available at https://github.com/technometrics-lab/17-The-determinants-of-cyberattack-costs-An-event-study. Corresponding author: Daniel Celeny e-mail: [email protected], Cyber-Defence Campus, Innovation Park, EPFL, 1015 Lausann

Do position and species identity of neighbours matter in 8–15-year-old post harvest mesic stands in the boreal mixedwood?

Neighbourhood competition indices (NCI), where position and species identity of neighbours are known, have been used to investigate growth and competitive interactions among adult trees. In this study, we used NCI in 8–15-year-old stands following clear-cutting in a boreal mixedwood forest of eastern Canada to improve our understanding of early successional forest dynamics. Trees of increasing diameter from the center (≥1 cm) to the edge (≥5 cm) were mapped in twenty-five circular 450m2 plots. Target trees (DBH≥1 cm) were sampled in plot center to determine their annual radial stem growth. For each species, we compared a set of growth models using either a spatially explicit NCI or a non-spatial competition index. Both types of indices estimated a species-specific competition coefficient for each pair of competitor–target species. NCI were selected as the best competition model for all target species although differences in variance explained relative to the non-spatial index were small. This likely indicates that competition occurs at the local level but that the high density and the relative uniformity of these young stands creates similar neighbourhoods for most trees in a given stand. The effective neighbourhood radius for competitors varied among species and was smaller for shade tolerant species. Intraspecific neighbours were the strongest competitors for most species. Aspen (Populus tremuloides) was a weak competitor for all species as opposed to balsam fir (Abies balsamea) which was a strong competitor in all cases. These results are in contradiction with some widely used forest policies in North America (e.g. free-to-grow standards) that consider broadleaf species, such as aspen, as the strongest competitors. For these early successional forests, the decision regarding the use of spatial or non-spatial competition indices should rest on the intended use. For even-age management, spatial indices might not justify their use in highdensity stands but they are needed for the simulation of novel harvest techniques creating complex stand structure

Masitinib Combined with Standard Gemcitabine Chemotherapy: In Vitro and In Vivo Studies in Human Pancreatic Tumour Cell Lines and Ectopic Mouse Model

International audienceBackground: Tyrosine kinases are attractive targets for pancreatic cancer therapy because several are over-expressed, including PDGFRα/β, FAK, Src and Lyn. A critical role of mast cells in the development of pancreatic cancer has also been reported. Masitinib is a tyrosine kinase inhibitor that selectively targets c-Kit, PDGFRα/β, Lyn, and to a lesser extent the FAK pathway, without inhibiting kinases of known toxicities. Masitinib is particularly efficient in controlling the proliferation, differentiation and degranulation of mast cells. This study evaluates the therapeutic potential of masitinib in pancreatic cancer, as a single agent and in combination with gemcitabine.Methodology/Findings: Proof-of-concept studies were performed in vitro on human pancreatic tumour cell lines and then in vivo using a mouse model of human pancreatic cancer. Molecular mechanisms were investigated via gene expression profiling. Masitinib as a single agent had no significant antiproliferative activity while the masitinib/gemcitabine combination showed synergy in vitro on proliferation of gemcitabine-refractory cell lines Mia Paca2 and Panc1, and to a lesser extent in vivo on Mia Paca2 cell tumour growth. Specifically, masitinib at 10 µM strongly sensitised Mia Paca2 cells to gemcitabine (>400-fold reduction in IC50); and moderately sensitised Panc1 cells (10-fold reduction). Transcriptional analysis identified the Wnt/β-catenin signalling pathway as down-regulated in the cell lines resensitised by the masitinib/gemcitabine combination.Conclusions: These data establish proof-of-concept that masitinib can sensitise gemcitabine-refractory pancreatic cancer cell lines and warrant further in vivo investigation. Indeed, such an effect has been recently observed in a phase 2 clinical study of patients with pancreatic cancer who received a masitinib/gemcitabine combination

Highly plastic genome of Microcystis aeruginosa PCC 7806, a ubiquitous toxic freshwater cyanobacterium

Background The colonial cyanobacterium Microcystis proliferates in a wide range of freshwater ecosystems and is exposed to changing environmental factors during its life cycle. Microcystis blooms are often toxic, potentially fatal to animals and humans, and may cause environmental problems. There has been little investigation of the genomics of these cyanobacteria. Results Deciphering the 5,172,804 bp sequence of Microcystis aeruginosa PCC 7806 has revealed the high plasticity of its genome: 11.7% DNA repeats containing more than 1,000 bases, 6.8% putative transposases and 21 putative restriction enzymes. Compared to the genomes of other cyanobacterial lineages, strain PCC 7806 contains a large number of atypical genes that may have been acquired by lateral transfers. Metabolic pathways, such as fermentation and a methionine salvage pathway, have been identified, Conclusion Microcystis aeruginosa PCC 7806 appears to have adopted an evolutionary strategy relying on unusual genome plasticity to adapt to eutrophic freshwater ecosystems, a property shared by another strain of M. aeruginosa (NIES-843). Comparisons of the genomes of PCC 7806 and other cyanobacterial strains indicate that a similar strategy may have also been used by the marine strain Crocosphaera watsonii WH8501 to adapt to other ecological niches, such as oligotrophic open oceans.

Topical ascorbic acid on photoaged skin. Clinical, topographical and ultrastructural evaluation: double-blind study vs. placebo.

peer reviewedaudience: researcherVitamin C is known for its antioxidant potential and activity in the collagen biosynthetic pathway. Photoprotective properties of topically applied vitamin C have also been demonstrated, placing this molecule as a potential candidate for use in the prevention and treatment of skin ageing. A topically applied cream containing 5% vitamin C and its excipient were tested on healthy female volunteers presenting with photoaged skin on their low-neck and arms in view to evaluate efficacy and safety of such treatment. A double-blind, randomized trial was performed over a 6-month period, comparing the action of the vitamin C cream vs. excipient on photoaged skin. Clinical assessments included evaluation at the beginning and after 3 and 6 months of daily treatment. They were performed by the investigator and compared with the volunteer self assessment. Skin relief parameters were determined on silicone rubber replicas performed at the same time-points. Cutaneous biopsies were obtained at the end of the trial and investigated using immunohistochemistry and electron microscopy. Clinical examination by a dermatologist as well as self-assessment by the volunteers disclosed a significant improvement, in terms of the 'global score', on the vitamin C-treated side compared with the control. A highly significant increase in the density of skin microrelief and a decrease of the deep furrows were demonstrated. Ultrastructural evidence of the elastic tissue repair was also obtained and well corroborated the favorable results of the clinical and skin surface examinations. Topical application of 5% vitamin C cream was an effective and well-tolerated treatment. It led to a clinically apparent improvement of the photodamaged skin and induced modifications of skin relief and ultrastructure, suggesting a positive influence of topical vitamin C on parameters characteristic for sun-induced skin ageing

Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT

International audienceBackground: The stem cell factor receptor, KIT, is a target for the treatment of cancer, mastocytosis, and inflammatory diseases. Here, we characterise the in vitro and in vivo profiles of masitinib (AB1010), a novel phenylaminothiazole-type tyrosine kinase inhibitor that targets KIT. Methodology/Principal Findings: In vitro, masitinib had greater activity and selectivity against KIT than imatinib, inhibiting recombinant human wild-type KIT with an half inhibitory concentration (IC50) of 200 ± 40 nM and blocking stem cell factor-induced proliferation and KIT tyrosine phosphorylation with an IC50 of 150 ± 80 nM in Ba/F3 cells expressing human or mouse wild-type KIT. Masitinib also potently inhibited recombinant PDGFR and the intracellular kinase Lyn, and to a lesser extent, fibroblast growth factor receptor 3. In contrast, masitinib demonstrated weak inhibition of ABL and c-Fms and was inactive against a variety of other tyrosine and serine/threonine kinases. This highly selective nature of masitinib suggests that it will exhibit a better safety profile than other tyrosine kinase inhibitors; indeed, masitinib-induced cardiotoxicity or genotoxicity has not been observed in animal studies. Molecular modelling and kinetic analysis suggest a different mode of binding than imatinib, and masitinib more strongly inhibited degranulation, cytokine production, and bone marrow mast cell migration than imatinib. Furthermore, masitinib potently inhibited human and murine KIT with activating mutations in the juxtamembrane domain. In vivo, masitinib blocked tumour growth in mice with subcutaneous grafts of Ba/F3 cells expressing a juxtamembrane KIT mutant. Conclusions: Masitinib is a potent and selective tyrosine kinase inhibitor targeting KIT that is active, orally bioavailable in vivo, and has low toxicit

Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1

Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti–IFN-β and another anti–IFN-ε, but none had anti–IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.publishedVersio