Contribution to failure description as the phenomena

We frequently work with the events´ description besides other assessments in safety/risk assessment. In pure technical applications these events are related with the failure occurrence of equipment, a device, a system or an item. This contribution can be a complex problem for the term “failure” and its related characteristics. In this paper there are mentioned functions of an object and their description, classification of failures, main characteristics of failure, possible causes of failure, mechanisms of failure and consequences of failure and also other contributions related with failure very closely

Selected Options of Vulnerability Assessment – State of the Art in Literature Review

The paper deals with the selected aspects of vulnerability assessment of systems. Historically, the vulnerability is recognised as one of the important aspects of system properties – system quality. The wide utilization of vulnerability can be observed in the IT area. Some approaches to vulnerability assessment are based on experiences and empiricism. For some other works it is necessary to have a quantitative value used for expressing vulnerability. In this paper we have applied the methods of analytical research, information search and a synthesis. They serve to introduce selected approaches expressing system vulnerability. The attention is paid mainly to the environmental and critical infrastructure systems. The results are presented in the form of definitions, equations or graphs. All these alternatives are further usable for assessing critical infrastructure elements. The results are also suitable for deeper development of a safety research scientific discipline

Natalizumab treatment shows low cumulative probabilities of confirmed disability worsening to EDSS milestones in the long-term setting.

Abstract Background Though the Expanded Disability Status Scale (EDSS) is commonly used to assess disability level in relapsing-remitting multiple sclerosis (RRMS), the criteria defining disability progression are used for patients with a wide range of baseline levels of disability in relatively short-term trials. As a result, not all EDSS changes carry the same weight in terms of future disability, and treatment benefits such as decreased risk of reaching particular disability milestones may not be reliably captured. The objectives of this analysis are to assess the probability of confirmed disability worsening to specific EDSS milestones (i.e., EDSS scores ≥3.0, ≥4.0, or ≥6.0) at 288 weeks in the Tysabri Observational Program (TOP) and to examine the impact of relapses occurring during natalizumab therapy in TOP patients who had received natalizumab for ≥24 months. Methods TOP is an ongoing, open-label, observational, prospective study of patients with RRMS in clinical practice. Enrolled patients were naive to natalizumab at treatment initiation or had received ≤3 doses at the time of enrollment. Intravenous natalizumab (300 mg) infusions were given every 4 weeks, and the EDSS was assessed at baseline and every 24 weeks during treatment. Results Of the 4161 patients enrolled in TOP with follow-up of at least 24 months, 3253 patients with available baseline EDSS scores had continued natalizumab treatment and 908 had discontinued (5.4% due to a reported lack of efficacy and 16.4% for other reasons) at the 24-month time point. Those who discontinued due to lack of efficacy had higher baseline EDSS scores (median 4.5 vs. 3.5), higher on-treatment relapse rates (0.82 vs. 0.23), and higher cumulative probabilities of EDSS worsening (16% vs. 9%) at 24 months than those completing therapy. Among 24-month completers, after approximately 5.5 years of natalizumab treatment, the cumulative probabilities of confirmed EDSS worsening by 1.0 and 2.0 points were 18.5% and 7.9%, respectively (24-week confirmation), and 13.5% and 5.3%, respectively (48-week confirmation). The risks of 24- and 48-week confirmed EDSS worsening were significantly higher in patients with on-treatment relapses than in those without relapses. An analysis of time to specific EDSS milestones showed that the probabilities of 48-week confirmed transition from EDSS scores of 0.0–2.0 to ≥3.0, 2.0–3.0 to ≥4.0, and 4.0–5.0 to ≥6.0 at week 288 in TOP were 11.1%, 11.8%, and 9.5%, respectively, with lower probabilities observed among patients without on-treatment relapses (8.1%, 8.4%, and 5.7%, respectively). Conclusions In TOP patients with a median (range) baseline EDSS score of 3.5 (0.0–9.5) who completed 24 months of natalizumab treatment, the rate of 48-week confirmed disability worsening events was below 15%; after approximately 5.5 years of natalizumab treatment, 86.5% and 94.7% of patients did not have EDSS score increases of ≥1.0 or ≥2.0 points, respectively. The presence of relapses was associated with higher rates of overall disability worsening. These results were confirmed by assessing transition to EDSS milestones. Lower rates of overall 48-week confirmed EDSS worsening and of transitioning from EDSS score 4.0–5.0 to ≥6.0 in the absence of relapses suggest that relapses remain a significant driver of disability worsening and that on-treatment relapses in natalizumab-treated patients are of prognostic importance

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Selected Options of Vulnerability Assessment – State of the Art in Literature Review

The paper deals with the selected aspects of vulnerability assessment of systems. Historically, the vulnerability is recognised as one of the important aspects of system properties – system quality. The wide utilization of vulnerability can be observed in the IT area. Some approaches to vulnerability assessment are based on experiences and empiricism. For some other works it is necessary to have a quantitative value used for expressing vulnerability. In this paper we have applied the methods of analytical research, information search and a synthesis. They serve to introduce selected approaches expressing system vulnerability. The attention is paid mainly to the environmental and critical infrastructure systems. The results are presented in the form of definitions, equations or graphs. All these alternatives are further usable for assessing critical infrastructure elements. The results are also suitable for deeper development of a safety research scientific discipline

Phenomena of a failure

In our lives we meet many events which have very diverse causes, mechanisms of development and consequences. We frequently work with the events´ description besides other assessments in safety/risk assessment. In pure technical applications these events are related with failure occurrence of equipment, a device, a system or an item. The theory speaks about failure itself, its mechanisms, circumstances of occurrence, etc. but at the same time we need appropriate terminology to describe these conditions. Our basic approaches into observing, dealing and handling failure may fall into two groups. We either talk about a probabilistic approach or about a deterministic (logic) approach. As we need to get some information about a failure we need to find it or transfer it from different sources. The contribution gives a small piece of very complex problematic of the term “failure” and its related characteristics. There are mentioned functions of an object and their description, classification of failures, main characteristics of failure, possible causes of failure, mechanisms of failure and consequences of failure and also other contributions related with failure very closely. The paper also deals with possible information sources which may inform us more on failure, and not only on typical characteristic

The failure phenomenon: a critique

Throughout every day life there are many events encountered where their causes, mechanisms of development and consequences are very diverse. In undertaking a safety or risk assessment it is the concept of the events´ description that is often of importance. In pure technical applications these events are related to the occurrence of failure, be it of equipment, a device, a system or an item. The theory speaks about failure itself, its mechanisms and circumstances of occurrence, but at the same time appropriate terminology is needed to describe these conditions. For observing, dealing and handling failures a probabilistic or deterministic (logic) approach can be followed. This paper considers the complex, sometimes problematic, area of the term “failure” and its related characteristics. The contribution aims to detail the total complexity of this fundamental term. A two fold objective approach is taken. The primary objective is to address each of these complexity issues providing an understanding of the key concepts and classifications. These are related to the functions of an object and their description, classification of failures, the main characteristics of failure, the possible causes of failure, mechanisms of failure and consequences of failure. Each of these issues can be subdivided and engineering examples are used to illustrate and differentiate between such subdivisions, for example to distinguish for failure occurrence the meaning of design failures, manufacturing failures and ageing failure etc. The secondary objective is related to information sources. To gain information about a failure it may need to be found or transferred from a variety of sources, these sources have been identified and discussed. In conclusion the paper serves to form a complete picture to aid the understanding and implications of failures

Prognozowanie niezawodności elementów sieci wodociągowej na podstawie rzadkich danych terenowych i modeli przestrzeni stanów

The elements of critical infrastructure have to meet demanding dependability, safety and security requirements. The article deals with the prognosis of water mains reliability while using sparse irregular filed data. The data are sparse because the only thing we know is the number of mains failures during a given month. Since it is possible to transform the data into a typical reliability measure (rate of failure occurrence – ROCOF), we can examine the course of this measure development in time. In order to model and predict the ROCOF development, we suggest novel single and multiple error state space models. The results can be used for i) optimizing mains operation and maintenance, ii) estimating life cycle cost, and iii) planning crisis management.Elementy infrastruktury krytycznej muszą spełniać wysokie wymagania w zakresie niezawodności, bezpieczeństwa i ochrony. Artykuł dotyczy prognozowania niezawodności sieci wodociągowej przy wykorzystaniu nieregularnie rejestrowanych rzadkich danych. Wykorzystane w pracy dane są rzadkie, ponieważ dostarczają jedynie informacji na temat liczby uszkodzeń wodociągu w danym miesiącu. Przekształcenie tych danych w typową miarę niezawodności (wskaźnik występowania uszkodzeń – ROCOF), pozwala zbadać przebieg rozwoju tej miary w czasie. Rozwój ROCOF można modelować i przewidywać za pomocą zaproponowanych w pracy innowacyjnych modeli przestrzeni stanów uwzględniających pojedynczy błąd lub wiele błędów. Uzyskane wyniki można wykorzystać do i) optymalizacji pracy i eksploatacji sieci wodociągowej, ii) szacowania kosztów cyklu życia, oraz iii) planowania zarządzania kryzysowego