114 research outputs found
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Ransomware detection using deep learning based unsupervised feature extraction and a cost sensitive Pareto Ensemble classifier
Ransomware attacks pose a serious threat to Internet resources due to their far-reaching effects. It's Zero-day variants are even more hazardous, as less is known about them. In this regard, when used for ransomware attack detection, conventional machine learning approaches may become data-dependent, insensitive to error cost, and thus may not tackle zero-day ransomware attacks. Zero-day ransomware have normally unseen underlying data distribution. This paper presents a Cost-Sensitive Pareto Ensemble strategy, CSPE-R to detect novel Ransomware attacks. Initially, the proposed framework exploits the unsupervised deep Contractive Auto Encoder (CAE) to transform the underlying varying feature space to a more uniform and core semantic feature space. To learn the robust features, the proposed CSPE-R ensemble technique explores different semantic spaces at various levels of detail. Heterogeneous base estimators are then trained over these extracted subspaces to find the core relevance between the various families of the ransomware attacks. Then, a novel Pareto Ensemble-based estimator selection strategy is implemented to achieve a cost-sensitive compromise between false positives and false negatives. Finally, the decision of selected estimators are aggregated to improve the detection against unknown ransomware attacks. The experimental results show that the proposed CSPE-R framework performs well against zero-day ransomware attacks
Co-producing a digital educational programme for registered childrenâs nurses to improve care of children and young people admitted with self-harm
Despite the increasing prevalence of hospital admissions for self-harm in children and young people (CYP), there is paucity of registered childrenâs nurse (rCN) training or involvement of children to improve care for this often stigmatized patient group. This article describes a participatory approach towards using co-production with CYP and rCN to develop a digital educational programme to improve nursesâ knowledge, attitudes and confidence in caring for CYP with self-harm injuries. A priority-setting workshop with rCNs was used to establish consensus of information needs. This was followed by an e-learning content development workshop undertaken with CYP whom had previously experienced hospital admissions for self-harm injuries. Findings from the nurse priority-setting workshop identified three educational priorities: (1) knowledge of self-harm, (2) effective communication and (3) risk management. The CYP subsequently developed these topic areas to ensure the contents and design of the e-learning resource had fidelity by reflecting the experiences of CYP and needs when cared for in hospital. This article illustrates that involving service users to co-develop educational materials is a feasible and important step in designing educational resources and ensures the content is relevant, appropriate and sensitive to both the recipient of care and those responsible for its delivery
Diagnosis of pericardial cysts using diffusion weighted magnetic resonance imaging: A case series
<p>Abstract</p> <p>Introduction</p> <p>Congenital pericardial cysts are benign lesions that arise from the pericardium during embryonic development. The diagnosis is based on typical imaging features, but atypical locations and signal magnetic resonance imaging sequences make it difficult to exclude other lesions. Diffusion-weighted magnetic resonance imaging is a novel method that can be used to differentiate tissues based on their restriction to proton diffusion. Its use in differentiating pericardial cysts from other pericardial lesions has not yet been described.</p> <p>Case presentation</p> <p>We present three cases (a 51-year-old Caucasian woman, a 66-year-old Caucasian woman and a 77-year-old Caucasian woman) with pericardial cysts evaluated with diffusion-weighted imaging using cardiac magnetic resonance imaging. Each lesion demonstrated a high apparent diffusion coefficient similar to that of free water.</p> <p>Conclusion</p> <p>This case series is the first attempt to investigate the utility of diffusion-weighted magnetic resonance imaging in the assessment of pericardial cysts. Diffusion-weighted imaging may be a useful noninvasive diagnostic tool for pericardial cysts when conventional imaging findings are inconclusive.</p
Collision-induced signal enhancement (CISE): The use of boundary activation to effect non-resonant CISE
Of shepherds, sheep and sheepdogs?: governing the adherent self through complementary and competing âpastoratesâ
Foucaultâs concept of âpastoral powerâ describes an important technique for constituting obedient subjects. Derived from his analysis of the Christian pastorate, he saw pastoral power as a prelude to contemporary technologies of governing âbeyond the Stateâ, where âexpertsâ shepherd self-governing subjects. However, the specific practices of modern pastorate have been little developed. This papers examines the relational practices of pastoral power associated with the government of medicine use within the English healthcare system. The study shows how multiple pastors align their complimentary and variegated practices to conduct behaviours, but also how pastors compete for legitimacy, and face resistance through the mobilisation of alternate discourses and the strategic exploitation of pastoral competition. The paper offers a dynamic view of the modern pastorate within the contemporary assemblages of power
Mutations in TOP3A Cause a Bloom Syndrome-like Disorder
Bloom syndrome, caused by biallelic mutations in BLM, is characterized by prenatal-onset growth deficiency, short stature, an erythematous photosensitive malar rash, and increased cancer predisposition. Diagnostically, a hallmark feature is the presence of increased sister chromatid exchanges (SCEs) on cytogenetic testing. Here, we describe biallelic mutations in TOP3A in ten individuals with prenatal-onset growth restriction and microcephaly. TOP3A encodes topoisomerase III alpha (TopIIIα), which binds to BLM as part of the BTRR complex, and promotes dissolution of double Holliday junctions arising during homologous recombination. We also identify a homozygous truncating variant in RMI1, which encodes another component of the BTRR complex, in two individuals with microcephalic dwarfism. The TOP3A mutations substantially reduce cellular levels of TopIIIα, and consequently subjectsâ cells demonstrate elevated rates of SCE. Unresolved DNA recombination and/or replication intermediates persist into mitosis, leading to chromosome segregation defects and genome instability that most likely explain the growth restriction seen in these subjects and in Bloom syndrome. Clinical features of mitochondrial dysfunction are evident in several individuals with biallelic TOP3A mutations, consistent with the recently reported additional function of TopIIIα in mitochondrial DNA decatenation. In summary, our findings establish TOP3A mutations as an additional cause of prenatal-onset short stature with increased cytogenetic SCEs and implicate the decatenation activity of the BTRR complex in their pathogenesis
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The REASON score: an epigenetic and clinicopathologic score to predict risk of poor survival in patients with early stage oral squamous cell carcinoma
Background
Oral squamous cell carcinoma (OSCC) is a capricious cancer with poor survival rates, even for early-stage patients. There is a pressing need to develop more precise risk assessment methods to appropriately tailor clinical treatment. Genome-wide association studies have not produced a viable biomarker. However, these studies are limited by using heterogeneous cohorts, not focusing on methylation although OSCC is a heavily epigenetically-regulated cancer, and not combining molecular data with clinicopathologic data for risk prediction. In this study we focused on early-stage (I/II) OSCC and created a risk score called the REASON score, which combines clinicopathologic characteristics with a 12-gene methylation signature, to predict the risk of 5-year mortality.
Methods
We combined data from an internal cohort (nâ=â515) and The Cancer Genome Atlas (TCGA) cohort (nâ=â58). We collected clinicopathologic data from both cohorts to derive the non-molecular portion of the REASON score. We then analyzed the TCGA cohort DNA methylation data to derive the molecular portion of the risk score.
Results
5-year disease specific survival was 63% for the internal cohort and 86% for the TCGA cohort. The clinicopathologic features with the highest predictive ability among the two the cohorts were age, race, sex, tobacco use, alcohol use, histologic grade, stage, perineural invasion (PNI), lymphovascular invasion (LVI), and margin status. This panel of 10 non-molecular features predicted 5-year mortality risk with a concordance (c)-indexâ=â0.67. Our molecular panel consisted of a 12-gene methylation signature (i.e., HORMAD2, MYLK, GPR133, SOX8, TRPA1, ABCA2, HGFAC, MCPH1, WDR86, CACNA1H, RNF216, CCNJL), which had the most significant differential methylation between patients who survived vs. died by 5âyears. All 12 genes have already been linked to survival in other cancers. Of the genes, only SOX8 was previously associated with OSCC; our study was the first to link the remaining 11 genes to OSCC survival. The combined molecular and non-molecular panel formed the REASON score, which predicted risk of death with a c-indexâ=â0.915.
Conclusions
The REASON score is a promising biomarker to predict risk of mortality in early-stage OSCC patients. Validation of the REASON score in a larger independent cohort is warranted
Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology.
Resident fibroblasts at sites of infection, chronic inflammation, or cancer undergo phenotypic and functional changes to support leukocyte migration and, in some cases, aggregation into tertiary lymphoid structures (TLS). The molecular programming that shapes these changes and the functional requirements of this population in TLS development are unclear. Here, we demonstrate that external triggers at mucosal sites are able to induce the progressive differentiation of a population of podoplanin (pdpn)-positive stromal cells into a network of immunofibroblasts that are able to support the earliest phases of TLS establishment. This program of events, that precedes lymphocyte infiltration in the tissue, is mediated by paracrine and autocrine signals mainly regulated by IL13. This initial fibroblast network is expanded and stabilized, once lymphocytes are recruited, by the local production of the cytokines IL22 and lymphotoxin. Interfering with this regulated program of events or depleting the immunofibroblasts in vivo results in abrogation of local pathology, demonstrating the functional role of immunofibroblasts in supporting TLS maintenance in the tissue and suggesting novel therapeutic targets in TLS-associated diseases
Mass spectrometric strategy for the characterization of lipooligosaccharides from Neisseria gonorrhoeae 302 using FTICR
Recovery and reuse of structural products from end-of-life buildings
YesBuildings and construction have been identified as having the greatest potential for circular economy value creation. One source of value creation is to recover and reuse building products from end-of-service-life buildings, rather than destructive demolition and downcycling. While there is a trade in non-structural and heritage product recovery and reuse, the largest volume, mass and value of most buildings comprise structural elements â concrete, brick and masonry, and steel â which present many challenges. A comprehensive literature review confirms limited attention to innovation and advanced techniques to address these challenges and therefore the potential reuse of the stocks of accumulated building products globally and associated environmental benefits. Potential techniques being tested in an Engineering and Physical Sciences Research Council circular economy research programme are referenced as a key building block towards circular economy building system redesign.Engineering and Physical Sciences Research Council - research project Rebuild (EPSRC EP/P008917/1
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