287 research outputs found
Risk and Business Goal Based Security Requirement and Countermeasure Prioritization
Companies are under pressure to be in control of their assets but at the same time they must operate as efficiently as possible. This means that they aim to implement “good-enough security” but need to be able to justify their security investment plans. Currently companies achieve this by means of checklist-based security assessments, but these methods are a way to achieve consensus without being able to provide justifications of countermeasures in terms of business goals. But such justifications are needed to operate securely and effectively in networked businesses. In this paper, we first compare a Risk-Based Requirements Prioritization method (RiskREP) with some requirements engineering and risk assessment methods based on their requirements elicitation and prioritization properties. RiskREP extends misuse case-based requirements engineering methods with IT architecture-based risk assessment and countermeasure definition and prioritization. Then, we present how RiskREP prioritizes countermeasures by linking business goals to countermeasure specification. Prioritizing countermeasures based on business goals is especially important to provide the stakeholders with structured arguments for choosing a set of countermeasures to implement. We illustrate RiskREP and how it prioritizes the countermeasures it elicits by an application to an action case
Некоторые проблемы добычи полезных ископаемых на глубоких горизонтах недр
Cardiovascular screening may benefit middle-aged sportsmen, as coronary artery disease (CAD) is the main cause of exercise-related sudden cardiac death. Arterial stiffness, as measured by pulse wave velocity (PWV), may help identify sportsmen with subclinical CAD. We examined the additional value of PWV measurements to traditional CAD risk factors for identifying CAD.From the Measuring Athlete's Risk of Cardiovascular events (MARC) cohort of asymptomatic, middle-aged sportsmen who underwent low-dose Cardiac CT (CCT) after routine sports medical examination (SME), 193 consecutive sportsmen (aged 55 ± 6.6 years) were included with additional PWV measurements before CCT. Sensitivity, specificity and predictive values of PWV values (>8.3 and >7.5 m/s) assessed by Arteriograph were used to identify CAD (coronary artery calcium scoring ≥ 100 Agatston Units or coronary CT angiography luminal stenosis ≥ 50%) and to assess the additional diagnostic value of PWV to established cardiovascular risk factors.Forty-seven sportsmen (24%) had CAD on CCT. They were older (58.9 vs. 53.8 years, p<0.001), had more hypertension (17 vs. 4%, p=0.003), higher cholesterol levels (5.7 vs. 5.4 mmol/l) p=0.048), and more often were (ever) smokers (55 vs. 34%, p=0.008). Mean PWV was higher in those with CAD (8.9 vs. 8.0 m/s, p=0.017). For PWV >8.3m/s respectively >7.5 m/s sensitivity to detect CAD on CT was 43% and 74%, specificity 69% and 45%, positive predictive value 31% and 30%, and negative predictive value 79% and 84%. Adding PWV to traditional risk factor models did not change the area under the curve (from 0.78 (95% CI = 0.709-0.848)) to AUC 0.78 (95% CI 0.710-0.848, p = 0.99)) for prediction of CAD on CCT.Limited additional value was found for PWV on top of established risk factors to identify CAD. PWV might still have a role to identify CAD in middle-aged sportsmen if risk factors such as cholesterol are unknown
Glucose regulation beyond hba<sub>1c</sub> in type 2 diabetes treated with insulin:Real-world evidence from the dialect-2 cohort
OBJECTIVE: To investigate glucose variations associated with glycated hemoglobin (HbA(1c)) in insulin-treated patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Patients included in Diabetes and Lifestyle Cohort Twente (DIALECT)-2 (n = 79) were grouped into three HbA(1c) categories: low, intermediate, and high (≤53, 54–62, and ≥63 mmol/mol or ≤7, 7.1–7.8, and ≥7.9%, respectively). Blood glucose time in range (TIR), time below range (TBR), time above range (TAR), glucose variability parameters, day and night duration, and frequency of TBR and TAR episodes were determined by continuous glucose monitoring (CGM) using the FreeStyle Libre sensor and compared between HbA(1c) categories. RESULTS: CGM was performed for a median (interquartile range) of 10 (7–12) days/patient. TIR was not different for low and intermediate HbA(1c) categories (76.8% [68.3–88.2] vs. 76.0% [72.5.0–80.1]), whereas in the low category, TBR was higher and TAR lower (7.7% [2.4–19.1] vs. 0.7% [0.3–6.1] and 8.2% [5.7–17.6] vs. 20.4% [11.6–27.0], respectively; P < 0.05). Patients in the highest HbA(1c) category had lower TIR (52.7% [40.9–67.3]) and higher TAR (44.1% [27.8–57.0]) than the other HbA(1c) categories (P < 0.05), but did not have less TBR during the night. All patients had more (0.06 ± 0.06/h vs. 0.03 ± 0.03/h; P = 0.002) and longer (88.0 [45.0–195.5] vs. 53.4 [34.4–82.8] minutes; P < 0.001) TBR episodes during the night than during the day. CONCLUSIONS: In this study, a high HbA(1c) did not reduce the occurrence of nocturnal hypoglycemia, and low HbA(1c) was not associated with the highest TIR. Optimal personalization of glycemic control requires the use of newer tools, including CGM-derived parameters
Investigating chromosomal instability in long-term survivors with glioblastoma and grade 4 astrocytoma
Background Only a small group of patients with glioblastoma multiforme (GBM) survives more than 36 months, so-called long-term survivors. Recent studies have shown that chromosomal instability (CIN) plays a prognostic and predictive role among different cancer types. Here, we compared histological (chromosome missegregation) and bioinformatic metrics (CIN signatures) of CIN in tumors of GBM typical survivors (<= 36 months overall survival), GBM long-term survivors and isocitrate dehydrogenase (IDH)-mutant grade 4 astrocytomas.Methods Tumor sections of all gliomas were examined for anaphases and chromosome missegregation. Further CIN signature activity analysis in the The Cancer Genome Atlas (TCGA)-GBM cohort was performed.Results Our data show that chromosome missegregation is pervasive in high grade gliomas and is not different between the 3 groups. We find only limited evidence of altered CIN levels in tumors of GBM long-term survivors relative to the other groups, since a significant depletion in CIN signature 11 relative to GBM typical survivors was the only alteration detected. In contrast, within IDH-mutant grade 4 astrocytomas we detected a significant enrichment of CIN signature 5 and 10 activities and a depletion of CIN signature 1 activity relative to tumors of GBM typical survivors.Conclusions Our data suggest that CIN is pervasive in high grade gliomas, however this is unlikely to be a major contributor to the phenomenon of long-term survivorship in GBM. Nevertheless, further evaluation of specific types of CIN (signatures) could have prognostic value in patients suffering from grade 4 gliomas
Investigating chromosomal instability in long-term survivors with glioblastoma and grade 4 astrocytoma
Background Only a small group of patients with glioblastoma multiforme (GBM) survives more than 36 months, so-called long-term survivors. Recent studies have shown that chromosomal instability (CIN) plays a prognostic and predictive role among different cancer types. Here, we compared histological (chromosome missegregation) and bioinformatic metrics (CIN signatures) of CIN in tumors of GBM typical survivors (<= 36 months overall survival), GBM long-term survivors and isocitrate dehydrogenase (IDH)-mutant grade 4 astrocytomas.Methods Tumor sections of all gliomas were examined for anaphases and chromosome missegregation. Further CIN signature activity analysis in the The Cancer Genome Atlas (TCGA)-GBM cohort was performed.Results Our data show that chromosome missegregation is pervasive in high grade gliomas and is not different between the 3 groups. We find only limited evidence of altered CIN levels in tumors of GBM long-term survivors relative to the other groups, since a significant depletion in CIN signature 11 relative to GBM typical survivors was the only alteration detected. In contrast, within IDH-mutant grade 4 astrocytomas we detected a significant enrichment of CIN signature 5 and 10 activities and a depletion of CIN signature 1 activity relative to tumors of GBM typical survivors.Conclusions Our data suggest that CIN is pervasive in high grade gliomas, however this is unlikely to be a major contributor to the phenomenon of long-term survivorship in GBM. Nevertheless, further evaluation of specific types of CIN (signatures) could have prognostic value in patients suffering from grade 4 gliomas
Low Physical Activity in Patients with Complicated Type 2 Diabetes Mellitus Is Associated with Low Muscle Mass and Low Protein Intake
Objective: In order to promote physical activity (PA) in patients with complicated type 2 diabetes, a better understanding of daily movement is required. We (1) objectively assessed PA in patients with type 2 diabetes, and (2) studied the association between muscle mass, dietary protein intake, and PA. Methods: We performed cross-sectional analyses in all patients included in the Diabetes and Lifestyle Cohort Twente (DIALECT) between November 2016 and November 2018. Patients were divided into four groups: = 10,000 steps/day. We studied the association between muscle mass (24 h urinary creatinine excretion rate, CER) and protein intake (by Maroni formula), and the main outcome variable PA (steps/day, Fitbit Flex device) using multivariate linear regression analyses. Results: In the 217 included patients, the median steps/day were 6118 (4115-8638). Of these patients, 48 patients (22%) took 7000-9999 steps/day, 37 patients (17%) took >= 10,000 steps/day, and 78 patients (36%) took = 10,000 steps/day, a higher body mass index (BMI) (33 +/- 6 vs. 30 +/- 5 kg/m(2), p = 0.009), lower CER (11.7 +/- 4.8 vs. 14.8 +/- 3.8 mmol/24 h, p = 0.001), and lower protein intake (0.84 +/- 0.29 vs. 1.08 +/- 0.22 g/kg/day, p < 0.001). Both creatinine excretion (beta = 0.26, p < 0.001) and dietary protein intake (beta = 0.31, p < 0.001) were strongly associated with PA, which remained unchanged after adjustment for potential confounders. Conclusions: Prevalent insufficient protein intake and low muscle mass co-exist in obese patients with low physical activity. Dedicated intervention studies are needed to study the role of sufficient protein intake and physical activity in increasing or maintaining muscle mass in patients with type 2 diabetes
White matter microstructure disruption in early stage amyloid pathology.
Introduction: Amyloid beta (Aβ) accumulation is the first pathological hallmark of Alzheimer's disease (AD), and it is associated with altered white matter (WM) microstructure. We aimed to investigate this relationship at a regional level in a cognitively unimpaired cohort. Methods: We included 179 individuals from the European Medical Information Framework for AD (EMIF‐AD) preclinAD study, who underwent diffusion magnetic resonance (MR) to determine tract‐level fractional anisotropy (FA); mean, radial, and axial diffusivity (MD/RD/AxD); and dynamic [18F]flutemetamol) positron emission tomography (PET) imaging to assess amyloid burden. Results: Regression analyses showed a non‐linear relationship between regional amyloid burden and WM microstructure. Low amyloid burden was associated with increased FA and decreased MD/RD/AxD, followed by decreased FA and increased MD/RD/AxD upon higher amyloid burden. The strongest association was observed between amyloid burden in the precuneus and body of the corpus callosum (CC) FA and diffusivity (MD/RD) measures. In addition, amyloid burden in the anterior cingulate cortex strongly related to AxD and RD measures in the genu CC. Discussion: Early amyloid deposition is associated with changes in WM microstructure. The non‐linear relationship might reflect multiple stages of axonal damage
Amyloid-driven disruption of default mode network connectivity in cognitively healthy individuals
Cortical accumulation of amyloid beta is one of the first events of Alzheimer's disease pathophysiology, and has been suggested to follow a consistent spatiotemporal ordering, starting in the posterior cingulate cortex, precuneus and medio-orbitofrontal cortex. These regions overlap with those of the default mode network, a brain network also involved in memory functions. Aberrant default mode network functional connectivity and higher network sparsity have been reported in prodromal and clinical Alzheimer's disease. We investigated the association between amyloid burden and default mode network connectivity in the preclinical stage of Alzheimer's disease and its association with longitudinal memory decline. We included 173 participants, in which amyloid burden was assessed both in CSF by the amyloid beta 42/40 ratio, capturing the soluble part of amyloid pathology, and in dynamic PET scans calculating the non-displaceable binding potential in early-stage regions. The default mode network was identified with resting-state functional MRI. Then, we calculated functional connectivity in the default mode network, derived from independent component analysis, and eigenvector centrality, a graph measure recursively defining important nodes on the base of their connection with other important nodes. Memory was tested at baseline, 2- and 4-year follow-up. We demonstrated that higher amyloid burden as measured by both CSF amyloid beta 42/40 ratio and non-displaceable binding potential in the posterior cingulate cortex was associated with lower functional connectivity in the default mode network. The association between amyloid burden (CSF and non-displaceable binding potential in the posterior cingulate cortex) and aberrant default mode network connectivity was confirmed at the voxel level with both functional connectivity and eigenvector centrality measures, and it was driven by voxel clusters localized in the precuneus, cingulate, angular and left middle temporal gyri. Moreover, we demonstrated that functional connectivity in the default mode network predicts longitudinal memory decline synergistically with regional amyloid burden, as measured by non-displaceable binding potential in the posterior cingulate cortex. Taken together, these results suggest that early amyloid beta deposition is associated with aberrant default mode network connectivity in cognitively healthy individuals and that default mode network connectivity markers can be used to identify subjects at risk of memory decline
In vivo tau pathology is associated with synaptic loss and altered synaptic function
BACKGROUND: The mechanism of synaptic loss in Alzheimer’s disease is poorly understood and may be associated with tau pathology. In this combined positron emission tomography (PET) and magnetoencephalography (MEG) study, we aimed to investigate spatial associations between regional tau pathology ([{18}^F]flortaucipir PET), synaptic density (synaptic vesicle 2A [11C]UCB-J PET) and synaptic function (MEG) in Alzheimer’s disease. METHODS: Seven amyloid-positive Alzheimer’s disease subjects from the Amsterdam Dementia Cohort underwent dynamic 130-minV [{18}^F]flortaucipir PET, dynamic 60-min [{11}^C]UCB-J PET with arterial sampling and 2 × 5-min resting-state MEG measurement. [{18^}F]flortaucipir- and [{11}^C]UCB-J-specific binding (binding potential, BPND) and MEG spectral measures (relative delta, theta and alpha power; broadband power; and peak frequency) were assessed in cortical brain regions of interest. Associations between regional [{18}^F]flortaucipir BPND, [{11}^C]UCB-J BP_{ND} and MEG spectral measures were assessed using Spearman correlations and generalized estimating equation models. RESULTS: Across subjects, higher regional [{18}^F]flortaucipir uptake was associated with lower [{11}^C]UCB-J uptake. Within subjects, the association between [{11}^C]UCB-J and [{18}^F]flortaucipir depended on within-subject neocortical tau load; negative associations were observed when neocortical tau load was high, gradually changing into opposite patterns with decreasing neocortical tau burden. Both higher [{18}^F]flortaucipir and lower [{11}^C]UCB-J uptake were associated with altered synaptic function, indicative of slowing of oscillatory activity, most pronounced in the occipital lobe. CONCLUSIONS: These results indicate that in Alzheimer’s disease, tau pathology is closely associated with reduced synaptic density and synaptic dysfunction
Commissioning of inline ECE system within waveguide based ECRH transmission systems on ASDEX upgrade
A CW capable inline electron cyclotron emission (ECE) separation system for feedback control, featuring oversized corrugated waveguides, is commissioned on ASDEX upgrade (AUG). The system is based on a combination of a polarization independent, non-resonant, Mach-Zehnder diplexer equipped with dielectric plate beam splitters [2, 3] employed as corrugated oversized waveguide filter, and a resonant Fast Directional Switch, FADIS [4, 5, 6, 7] as ECE/ECCD separation system. This paper presents an overview of the system, the low power characterisation tests and first high power commissioning on AUG
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