A Revised Forensic Process for Aligning the Investigation Process with the Design of Forensic-Enabled Cloud Services

© Springer Nature Switzerland AG 2020. The design and implementation of cloud services, without taking under consideration the forensic requirements and the investigation process, makes the acquisition and examination of data, complex and demanding. The evidence gathered from the cloud may not become acceptable and admissible in the court. A literature gap in supporting software engineers so as to elicit and model forensic-related requirements exists. In order to fill the gap, software engineers should develop cloud services in a forensically sound manner. In this paper, a brief description of the cloud forensic-enabled framework is presented (adding some new elements) so as to understand the role of the design of forensic-enabled cloud services in a cloud forensic investigation. A validation of the forensic requirements is also produced by aligning the stages of cloud forensic investigation process with the framework’s forensic requirements. In this way, on one hand, a strong relationship is built between these two elements and emphasis is given to the role of the forensic requirements and their necessity in supporting the investigation process. On the other hand, the alignment assists towards the identification of the degree of the forensic readiness of a cloud service against a forensic investigation

A framework for designing cloud forensic‑enabled services (CFeS)

Cloud computing is used by consumers to access cloud services. Malicious actors exploit vulnerabilities of cloud services to attack consumers. The link between these two assumptions is the cloud service. Although cloud forensics assists in the direction of investigating and solving cloud-based cyber-crimes, in many cases the design and implementation of cloud services falls back. Software designers and engineers should focus their attention on the design and implementation of cloud services that can be investigated in a forensic sound manner. This paper presents a methodology that aims on assisting designers to design cloud forensic-enabled services. The methodology supports the design of cloud services by implementing a number of steps to make the services cloud forensic-enabled. It consists of a set of cloud forensic constraints, a modelling language expressed through a conceptual model and a process based on the concepts identified and presented in the model. The main advantage of the proposed methodology is the correlation of cloud services’ characteristics with the cloud investigation while providing software engineers the ability to design and implement cloud forensic-enabled services via the use of a set of predefined forensic related task

Juvenile Dermatomyositis: what comes next? Long-term outcomes in childhood myositis from a patient perspective

BACKGROUND: To describe long-term outcomes in JDM using patient questionnaires and link to longitudinal, prospectively collected data for each patient within the Juvenile Dermatomyositis Cohort and Biomarker Study, UK and Ireland (JDCBS) to determine outcome predictors.  METHODS: JDCBS participants aged ≥ 16y completed the SF36, HAQ and a questionnaire regarding current disease features, medications, education and employment. Data collected from the JDCBS included disease subtype, demographics, clinical and laboratory features. Intensity indices were calculated for physician VAS, modified skin DAS, CMAS and MMT8 by dividing area under the curve (AUC) from longitudinal score trajectories by duration of study follow-up (y). Relationships between questionnaire and JDCBS clinical / laboratory data were investigated fitting statistical models appropriate for cross sectional and longitudinal data. RESULTS: Of 190 questionnaires sent, 84 (44%) were returned. Average age of respondents was 20.6 years (SD 3.9), time since diagnosis was 12.4 years (SD 5.0), age at onset was 9.2 years (SD 4.3), female to male ratio 4.25:1. Forty-nine (59%) self-reported persistently active disease, 54 (65%) were still taking immunosuppressive medication. 14/32 at school/higher education reported myositis adversely affecting academic results. 18–24 year-olds were twice as likely to be unemployed compared the UK population (OR = 0.456, 95% CI 0.24, 0.84, p = 0.001). Participants ≥ 18 years were three times as likely to be living with a parent/guardian (OR = 3.39, p < 0.001). SF36 MCS and MMT8 intensity index scores were significantly correlated (ρ = 0.328, p = 0.007). CONCLUSIONS: After 12.4 years, questionnaire responders reported self-perceived high rates of persistently active disease and medication use, reduced rates of employment and were more likely to live with a parent/guardian. Perceived persistently active muscle disease appeared to affect quality of life in these patients and was the most significant contributor to long-term outcomes. Our findings highlight the importance of including the patient perspective in the assessment of long term outcomes, so that that we can start to target initial management strategies more effectively based on a combination of clinical and patient-reported data

Efficacy and Safety of Cyclophosphamide Treatment in Severe Juvenile Dermatomyositis Shown by Marginal Structural Modeling

OBJECTIVE: In patients with severe or refractory juvenile dermatomyositis (JDM), second-line treatments may be required. Cyclophosphamide (CYC) is used to treat some connective tissue diseases, but evidence of efficacy in JDM is limited. This study aimed to describe clinical improvement in JDM patients treated with CYC and model efficacy of CYC compared to patients not treated with CYC. METHODS: Clinical data on skin, global and muscle disease were analyzed from patients recruited to the Juvenile Dermatomyositis Cohort and Biomarker Study. Clinical improvement following CYC treatment was described using unadjusted analysis. Marginal structural models (MSMs) were used to model treatment efficacy and adjust for confounding by indication. RESULTS: Compared to CYC start, there were reductions at 6, 12 and 24 months in skin disease (p=1.3×10-10 ), global disease (p=2.4×10-8 ), and muscle disease (p=8.0×10-10 ) for n=56 patients treated with CYC in unadjusted analysis. Limited evidence suggested reduction in glucocorticoid dose (p=0.047) in patients treated with CYC. MSM analysis showed reduced global disease and skin disease in patients who started CYC treatment over 12 months ago compared to patients never or not yet treated with CYC. In these patients, modified disease activity score for skin disease was 1.19 units lower (p=0.0085) and physician's global assessment was 0.66 units lower (p=0.027). Minor adverse events were reported in 3 patients within 1 year of stopping CYC. CONCLUSION: CYC is efficacious with no short-term side-effects seen in this study. Improvements in skin, global and muscle disease were observed. Further studies are required to evaluate longer-term side-effects. This article is protected by copyright. All rights reserved

Anti-HMGCR Autoantibodies in Juvenile Idiopathic Inflammatory Myopathies Identify a Rare but Clinically Important Subset of Patients

OBJECTIVE: We aimed to establish the prevalence and clinical associations of anti-HMG-CoA-reductase (anti-HMGCR) in a large UK cohort with juvenile myositis. METHODS: There were 381 patients investigated for anti-HMGCR using ELISA. RESULTS: Anti-HMGCR autoantibodies were detected in 4 patients (1%). These children had no or minimal rash and significant muscle disease. Muscle biopsies were considered distinctive, with widespread variation in fiber size, necrotic fibers, and chronic inflammatory cell infiltrates; all had prolonged elevation of creatine kinase and all ultimately received biologic therapies. CONCLUSION: Anti-HMGCR in UK children with myositis are associated with severe disease that is poorly responsive to standard treatment

Muscle biopsy in combination with myositis-specific autoantibodies aids prediction of outcomes in juvenile dermatomyositis

OBJECTIVE: Juvenile dermatomyositis (JDM) is a rare and severe autoimmune condition characterized by rash and proximal muscle weakness. While some patients respond to standard treatment, others do not. We investigated whether histopathology and myositis-specific autoantibodies (MSA) have prognostic significance. // METHODS: Muscle biopsy samples (n=101) from the UK JDM Cohort and Biomarker Study were stained, analyzed and scored. Autoantibodies were measured (n=90) and longitudinal clinical data were collected (median follow-up 4.9 years). Long-term treatment status was modelled using generalized estimating equations. // RESULTS: Muscle biopsy scores differed according to MSA. When effects of MSA were accounted for, increased severity of muscle pathology predicted increased risk of remaining on treatment over time: 1.48-fold higher odds (1.12-1.96, p=0.0058) for the global pathology score (hVAS) and 1.10-fold higher odds (1.01-1.21, p=0.038) for the total biopsy score for the standardized score tool. A protective effect was identified in patients with anti-Mi2 autoantibodies, who had 7.06-fold lower odds (1.41-35.36, p=0.018) of remaining on treatment, despite displaying more severe muscle pathology at biopsy. For patients with anti-NXP-2, anti-TIF1γ autoantibodies or no-detectable autoantibody, increased severity of muscle pathology alone could predict the risk of remaining on treatment, without adjustment for MSA: 1.61-fold higher odds (1.16-2.22, p=0.0040) for hVAS and 1.13-fold higher odds (1.03-1.24, p=0.013) for total biopsy score. // CONCLUSION: Muscle pathology, in combination with MSA, predicts the risk of remaining on treatment in JDM and may be useful for discussing probable treatment length with parents and patients. Understanding these associations may identify patients at greater risk of severe disease

Histological heterogeneity in a large clinical cohort of juvenile idiopathic inflammatory myopathy: analysis by myositis autoantibody and pathological features

AIM: Juvenile idiopathic inflammatory myopathies (IIM) have been recently reclassified into clinico-serological subgroups. Myopathological correlates of the subgroups are incompletely understood. METHODS: We studied muscle biopsies from 101 children with clinically and serologically-defined juvenile IIM from the UK JDM Cohort and Biomarker Study by applying the international JDM score tool, myopathological review, and C5b-9 complement analysis. RESULTS: Autoantibody data were available for 90/101 cases with 18/90 cases positive for anti-TIF1γ, 15/90 anti-NXP2, 11/90 anti-MDA5, 5/90 anti-Mi2, and 6/90 anti-PmScl. JDM biopsy severity scores were consistently low in the anti-MDA5 group, high in the anti-Mi2 group, and widely distributed in the other groups. Biopsies were classified histologically as perifascicular atrophy (22/101), macrophage-rich necrosis (6/101), scattered necrosis (2/101), clustered necrosis (2/101), inflammatory fibre invasion (2/101), chronic myopathic change (1/101), diffuse endomysial macrophage infiltrates (40/101), and minimal change (24/101). MDA5 cases segregated with the minimal change group and showed no capillary C5b-9-deposition. The Mi2 group displayed high severity scores and a tendency towards sarcolemmal complement deposition. NXP2 and TIF1γ groups showed a variety of pathologies with a high proportion of diffuse endomysial macrophage infiltrates and a high proportion of capillary C5b-9 deposition. CONCLUSION: We have shown that juvenile idiopathic inflammatory myopathies have a spectrum of histopathological phenotypes and show distinct complement attack complex deposition patterns. Both correlate in some cases with the serological subtypes. Most cases do not show typical histological features associated with dermatomyositis (e.g. perifascicular atrophy). In contrast, more than half show relatively mild histopathological changes. This article is protected by copyright. All rights reserved