Process hazard and operability analysis of BPCS and SIS malicious manipulations by POROS 2.0

The increasing interconnectivity with external networks and the higher reliance on digital systems make the facilities of the chemical, process, and Oil&Gas industry more vulnerable to cyber-attacks. These attacks have the potential of causing events with severe consequences on property, people, and the surrounding environment such as major event scenarios. The application of the currently available methodologies for cyber risk identification to complex plants with a large number of units may be demanding and cumbersome. The present study proposes an updated methodology, named POROS 2.0, that allows reducing time and effort in application by limiting the scope of the analysis to relevant cybersecurity scenarios. The latter are identified by investigating the potential escalation of consequences propagating among process and/or utility nodes of the manipulations of BPCS and SIS, similar to what is done in the HazOp technique in the safety domain. POROS 2.0 was demonstrated by the application to a case study addressing a fixed offshore platform for gas exploitation

Clinical and Epidemiological Study on Tubercular Uveitis in a Tertiary Eye Care Centre in Italy

PURPOSE: To describe frequency, clinical characteristics, and visual prognosis of tubercular uveitis (TBU) in a nonendemic country. METHODS: We retrospectively reviewed 3743 charts of patients with endogenous uveitis visited from 2008 to 2018 at a tertiary referral centre in Rome, Italy. We included immunocompetent patients with diagnosis of TBU. Patients were divided in two groups: patients with history of uveitis without a previous diagnosis of TBU (group A) and patients at their first episode of TB uveitis (group B). RESULTS: TBU was diagnosed in 28 (0.75%) out of 3743 patients. Twelve (42.9%) patients came from tuberculosis endemic areas. All patients received specific antitubercular treatment (ATT) and were evaluated for a mean follow-up of 3.2 ± 2.9 years. Group A showed a greater number of ocular complications when compared with group B. ATT was effective in reducing the frequency of recurrences of uveitis in patients of group B. CONCLUSION: Intraocular inflammation can be the first manifestation of tuberculosis. Our data highlight that early diagnosis and specific treatment of TBU may allow to decrease recurrences and to improve visual outcomes

Is physician assessment of alcohol consumption useful in predicting risk of severe liver disease among people with HIV and HIV/HCV co-infection?

Background: Alcohol consumption is a known risk factor for liver disease in HIV-infected populations. Therefore, knowledge of alcohol consumption behaviour and risk of disease progression associated with hazardous drinking are important in the overall management of HIV disease. We aimed at assessing the usefulness of routine data collected on alcohol consumption in predicting risk of severe liver disease (SLD) among people living with HIV (PLWHIV) with or without hepatitis C infection seen for routine clinical care in Italy. Methods: We included PLWHIV from two observational cohorts in Italy (ICONA and HepaICONA). Alcohol consumption was assessed by physician interview and categorized according to the National Institute for Food and Nutrition Italian guidelines into four categories: abstainer; moderate; hazardous and unknown. SLD was defined as presence of FIB4 > 3.25 or a clinical diagnosis of liver disease or liver-related death. Cox regression analysis was used to evaluate the association between level of alcohol consumption at baseline and risk of SLD. Results: Among 9542 included PLWHIV the distribution of alcohol consumption categories was: abstainers 3422 (36%), moderate drinkers 2279 (23%), hazardous drinkers 637 (7%) and unknown 3204 (34%). Compared to moderate drinkers, hazardous drinking was associated with higher risk of SLD (adjusted hazard ratio, aHR = 1.45; 95% CI: 1.03-2.03). After additionally controlling for mode of HIV transmission, HCV infection and smoking, the association was attenuated (aHR = 1.32; 95% CI: 0.94-1.85). There was no evidence that the association was stronger when restricting to the HIV/HCV co-infected population. Conclusions: Using a brief physician interview, we found evidence for an association between hazardous alcohol consumption and subsequent risk of SLD among PLWHIV, but this was not independent of HIV mode of transmission, HCV-infection and smoking. More efforts should be made to improve quality and validity of data on alcohol consumption in cohorts of HIV/HCV-infected individuals

Determinants of worse liver‐related outcome according to HDV infection among HBsAg positive persons living with HIV: Data from the ICONA cohort

Objectives: We aimed to study hepatitis D virus (HDV) prevalence and risk of progression to severe liver-related events (SLRE) in HBsAg positive people living with HIV (PLWH) in Italy; role of HDV-RNA copy levels, HCV coinfection and nadir CD4 counts were also investigated.Methods: People living with HIV (PLWH) from Italian Foundation cohort Naive antiretrovirals (ICONA) with available HBsAg and HDV Ab were enrolled. HBsAg, HDV Ab, HDV-RNA and HDV genotypes were tested. Primary end-point: time from first HDV screening to Severe Liver Related Events (SLRE: decompensated cirrhosis, liver transplantation, HCC). Fine-grey regression models were used to evaluate the association of HDV Ab, HDV-RNA, HDV/HCV coinfection, CD4 nadir and outcome. Secondary end-points: time to SLRE or death; HDV Ab and HDV-RNA prevalence.Results: A total of 152/809 (18.8%) HBsAg positive PLWH showed HDV Ab reactivity; 63/93 (67.7%) were HDV-RNA positive. Being male, persons who inject drugs (PWID), HCV Ab positive, with FIB-4 > 3.25 were independent factors of HDV Ab positivity. In a median follow-up of 5 years, 37 PLWH (4.1% at 5-year) developed SLRE and 97 (12.0%) reached the SLRE or death end-point. HDV-RNA positive (independently from HDV-RNA copy level) PLWH had a 4.6-fold (95%CI 2.0-10.5) higher risk of SLRE than HDV negatives. PLWH positive for both HCV Ab and HDV Ab showed the highest independent risk of SLRE (ASHR: 11.9, 95%CI: 4.6-30.9 vs. HCV neg/HDV neg). Nadir CD4 < 200/mL was associated with SLRE (ASHR: 3.9, 95% 1.0-14.5).Conclusions: One-fifth of the HBsAg positive PLWH harbour HDV infection, and are at high risk of progression to advanced liver disease. HCV contributes to worse outcomes. This population needs urgently effective treatments

Switching to dual/monotherapy determines an increase in CD8+ in HIV-infected individuals: An observational cohort study

Background: The CD4/CD8 ratio has been associated with the risk of AIDS and non-AIDS events. We describe trends in immunological parameters in people who underwent a switch to monotherapy or dual therapy, compared to a control group remaining on triple antiretroviral therapy (ART). Methods: We included patients in Icona who started a three-drug combination ART regimen from an ART-naïve status and achieved a viral load ≤ 50 copies/mL; they were subsequently switched to another triple or to a mono or double regimen. Standard linear regression at fixed points in time (12-24 months after the switch) and linear mixed model analysis with random intercepts and slopes were used to compare CD4 and CD8 counts and their ratio over time according to regimen types (triple vs. dual and vs. mono). Results: A total of 1241 patients were included; 1073 switched to triple regimens, 104 to dual (72 with 1 nucleoside reverse transcriptase inhibitor (NRTI), 32 NRTI-sparing), and 64 to monotherapy. At 12 months after the switch, for the multivariable linear regression the mean change in the log10 CD4/CD8 ratio for patients on dual therapy was -0.03 (95% confidence interval (CI) -0.05, -0.0002), and the mean change in CD8 count was +99 (95% CI +12.1, +186.3), taking those on triple therapy as reference. In contrast, there was no evidence for a difference in CD4 count change. When using all counts, there was evidence for a significant difference in the slope of the ratio and CD8 count between people who were switched to triple (points/year change ratio = +0.056, CD8 = -25.7) and those to dual regimen (ratio = -0.029, CD8 = +110.4). Conclusions: We found an increase in CD8 lymphocytes in people who were switched to dual regimens compared to those who were switched to triple. Patients on monotherapy did not show significant differences. The long-term implications of this difference should be ascertained

Is HCV elimination among persons living with HIV feasible? Data from the NoCo study in the setting of the ICONA cohort

Background and aims: Whether the HCV test-and-treat strategy impacted on the rate of new HCV infections among PLWH in Italy is unknown. Methods: Prospective study of PLWH in the ICONA network. At baseline, PLWH were tested for HCV-Ab; HCV-RNA (if HCV-Ab positive) and, if positive, treated with DAA. SVR12 indicated eradication. Seroconversions and re-infections were evaluated yearly in HCV-Ab neg and HCV-RNA neg at first screening. We estimated the following: HCV seroconversions, incidence of HCV reinfections, and access to DAA and SVR12 rates tighter with factors associated with each outcome. Data were analysed by Cox regression, Poisson regression and logistic regression models. Results: Sixteen thousand seven hundred and forty-three PLWH were included; 27.3% HCV-Ab positive; of these, 39.3% HCV-RNA positive. HCV seroconversion incidence: .48/100 PYFU (95% CI: .36-.65); re-infections incidence: 1.40/100 PYFU (95% CI: .91-2.04). The risk factor for HCV re-infection was young age: aIRR 1.85, 95% CI: 1.17-2.95) per 10 years younger. 86.4% of HCV viremic in follow-up started DAA. PWID vs. heterosexuals (aHR .75, 95% CI .62-.90), HIV-RNA >50 copies/mL (aHR .70, 95% CI .56-.87), HCV genotype other than G1, G2, G3, G4 or with multiple/missing HCV genotype and post-COVID-19 calendar periods were associated with lower DAA access. 922/965 (95.5%) PLWH achieved SVR12. We estimated 72% reduction of chance to achieve SVR12 in PLWH with a CD4 count <200/mm3 (vs. CD4 ≥200/mm3 aOR .18, 95% CI: .07-.46). 95.5% of DAA-treated individuals eradicated HCV, but they represent only 53.2% of HCV viremic PLWH and 66.4% of those in follow-up. HCV-RNA positivity by year decreased from 41.7% in 2017 to 11.7% in 2022. Conclusions: The screening-and-treat campaign implemented in Italy, even if only partially effective, resulted in a dramatic drop in HCV circulation in our cohort

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Cyber Threats Affecting the Process Industry and Similar Sectors

Cyber threats are becoming a growing concern for industrial facilities characterized by a high degree of automation, especially those that highly rely on Operational Technology (OT) systems such as process facilities. Fixed installations where chemical and petroleum products are manufactured and stored (e.g. Seveso sites in EU) are of primary concern since attackers may exploit their inherent hazardous conditions and trigger events with severe consequences on workers, population, the environment, and the company itself (e.g. major accidents). The study is based on the development of a database of 82 cybersecurity-related incidents (CSIs) and its analysis using Exploratory Data Analysis (EDA). Time-trend (from 1975 to 2020), geographical distribution, distribution among the industrial sectors, impacts of the incidents, and type of attackers (intentional external / intentional internal / accidental) were investigated, evidencing important findings. The attacks resulted to be able to affect not only the company Information Technology (IT) system, which is a threat common to several business sectors, but also to manipulate the control and safety systems (OT). Finally, the analysis of a sub-set of incidents with more detailed information allowed to identify the general phases of a cyber-attack to IT-OT systems of a process facility. The information obtained can be used to support the application of the techniques commonly used to handle security-risks in process facilities, such as Security Vulnerability Assessment (SVA) methodologies

A systematic methodology for the identification of major accidents induced by malicious manipulation of the bpcs and the sis in a process plant

Cyber-attacks aimed to interfere with the Basic Process Control System (BPCS) and the SIS (Safety Instrumented System) of industrial facilities where large quantities of hazardous substances are stored or handled may have consequences comparable to those of conventional major accidents due to internal causes. While consolidated approaches exist to manage and control the cybersecurity of IT (Information Technology) and OT (Operational Technology) systems of a plant, there is an evident lack of operating procedures for assessing the actual link between malicious manipulations of the BPCS and the SIS (OT system) and the major accidents that can be induced. In the present study a specific operating systematic methodology, PHAROS, was developed to address the identification of major accident scenarios achievable by remote manipulation of the physical components of the plant (e.g. automatic valves, pumps, compressors, etc.). The methodology exploits a reverse-HazOp concept and it also supports the definition of the specifications for the design and management of barriers aimed at the prevention and mitigation of such scenarios. The application of PHAROS to a demonstrative case study evidenced first that both the BPCS and the SIS typically need to be attacked in order to induce major accidents, and second, that passive/inherent safeguards have a key role with respect to the success of the considered malicious attack in case they are properly designed

Major accidents triggered by malicious manipulations of the control system in process facilities

Security threats on the industrial automated control systems (IACSs) are becoming a growing concern for all the industrial facilities, and in particular for those where large quantities of hazardous substances are stored or handled (e.g. Seveso sites in Europe). Remote (cyber) or physical malicious manipulations of the automated control system of Seveso sites may have consequences comparable to those of conventional major accidents due to internal causes (e.g. loss of containment of hazardous materials, fires, explosions). While consolidated approaches exist to manage and control the cybersecurity of IT and OT systems of a facility, there is an evident lack of procedures to assess the actual link between malicious manipulations of the safety and control systems and the major accidents that can be triggered. In the present study, a specific methodology (PHAROS) was developed to address the identification of major accident scenarios achievable by malicious manipulation of physical components of the plant through the control and safety instrumented systems. The methodology, which exploits a reverse-HazOp concept, also analyses the role of the existing safety barriers in contrasting the chain of events triggered by the malicious manipulation, and may support the definition of design specifications and/or possible IT protection requirements for such barriers. The methodology was applied to a demonstrative case study to understand the features of the results obtained and their potential towards the improvement of the security of the process facility