STPA Based Approach for a Resilience Assessment at an Early Design Stage of a Cruise Ship

Several definitions and approaches have been proposed to study resilience in different fields like materials, ecology, psychology and infrastructures. A general definition, applicable also to human-made or engineered systems, describes resilience as the ability to maintain capability in case of disruption. Thanks to its systemic, top-down approach, STAMP (System-Theoretic Accident Model and Processes) has been already identified in literature as a very effective and \u201cconductive\u201d reference when reasoning about the possible need of resilience of a complex system. The STAMP-based tool named STPA (System Theoretic Process Analysis) establishes the following steps: identify system accidents, hazards; draw functional control structure; identify unsafe control actions (UCAs); identify accident scenarios; formulate decisions and recommendations. It focuses on what actually is in the hands of the system designer and operator i.e. the possibility to take action on hazards that can be eliminated or controlled. In this paper an approach to design resilience into a cruise vessel will be proposed. An application case will be developed considering the specific hazard of dead ship condition i.e. of energy black-out on board. In case of navigation close to the shore and in heavy weather condition, this situation can rapidly evolve into a loss. The ship energy production and delivery system, both for the propulsion and for the hotel services, will be considered. Running the procedure up to the level of UCAs enables the identification of the possible disruptive events capable to degrade the operational performance of the system. Starting from this point, suggestions will be discussed for a selected UCA, able to prevent or mitigate it. A metric for ship resilience will be proposed as well with the aim to allow comparisons among different design solutions

Models and methods to characterise levonorgestrel release from intradermally administered contraceptives

Microneedle (MN)-based technologies have been proposed as a means to facilitate minimally invasive sustained delivery of long-acting hormonal contraceptives into the skin. Intradermal administration is a new route of delivery for these contraceptives and therefore no established laboratory methods or experimental models are available to predict dermal drug release and pharmacokinetics from candidate MN formulations. This study evaluates an in vitro release (IVR) medium and a medium supplemented with ex vivo human skin homogenate (SH) as potential laboratory models to investigate the dermal release characteristics of one such hormonal contraceptive that is being tested for MN delivery, levonorgestrel (LNG), and provides details of an accompanying novel two-step liquid–liquid drug extraction procedure and sensitive reversed-phase HPLC–UV assay. The extraction efficiency of LNG was 91.7 ± 3.06% from IVR medium and 84.6 ± 1.6% from the medium supplemented with SH. The HPLC–UV methodology had a limit of quantification of 0.005 µg/mL and linearity between 0.005 and 25 µg/mL. Extraction and detection methods for LNG were exemplified in both models using the well-characterised, commercially available sustained-release implant (Jadelle®). Sustained LNG release from the implant was detected in both media over 28 days. This study reports for the first time the use of biologically relevant release models and a rapid, reliable and sensitive methodology to determine release characteristics of LNG from intradermally administered long-acting drug delivery systems

Hollow silicon microneedle fabrication using advanced plasma etch technologies for applications in transdermal drug delivery

A novel production process flow is presented here for the manufacture of hollow silicon microneedles using deep reactive-ion etching (DRIE) technology. The patent-pending three-step process flow has been developed to produce multiple arrays of sharp-tipped, hollow microneedles, which facilitate easy insertion and controlled fluid injection into excised skin samples. A bevelled tip and vertical sidewalls for the microneedle have been achieved with good uniformity, despite >45% open etch area. Processing steps and etch challenges are discussed, and preliminary skin testing results are presented, showing effective needle insertion and delivery of fluorescent dye into ex vivo skin from human breast tissue

How Covid-19 changed the epidemiology of febrile urinary tract infections in children in the emergency department during the first outbreak

Background: The first Covid-19 pandemic affected the epidemiology of several diseases. A general reduction in the emergency department (ED) accesses was observed during this period, both in adult and pediatric contexts. Methods: This retrospective study was conducted on the behalf of the Italian Society of Pediatric Nephrology (SINePe) in 17 Italian pediatric EDs in March and April 2020, comparing them with data from the same periods in 2018 and 2019. The total number of pediatric (age 0–18 years) ED visits, the number of febrile urinary tract infection (UTI) diagnoses, and clinical and laboratory parameters were retrospectively collected. Results: The total number of febrile UTI diagnoses was 339 (73 in 2020, 140 in 2019, and 126 in 2018). During the first Covid-19 pandemic, the total number of ED visits decreased by 75.1%, the total number of febrile UTI diagnoses by 45.1%, with an increase in the UTI diagnosis rate (+ 121.7%). The data collected revealed an increased rate of patients with two or more days of fever before admission (p = 0.02), a significant increase in hospitalization rate (+ 17.5%, p = 0.008) and also in values of C reactive protein (CRP) (p = 0.006). In 2020, intravenous antibiotics use was significantly higher than in 2018 and 2019 (+ 15%, p = 0.025). Urine cultures showed higher Pseudomonas aeruginosa and Enterococcus faecalis percentages and lower rates of Escherichia coli (p = 0.02). Conclusions: The first wave of the Covid-19 pandemic had an essential impact on managing febrile UTIs in the ED, causing an absolute reduction of cases referring to the ED but with higher clinical severity. Children with febrile UTI were more severely ill than the previous two years, probably due to delayed access caused by the fear of potential hospital-acquired Sars-Cov-2 infection. The possible increase in consequent kidney scarring in this population should be considered

Design, fabrication, and characterisation of a silicon microneedle array for transdermal therapeutic delivery using a single step wet etch process

The fabrication of silicon in-plane microneedle arrays from a simple single wet etch step is presented. The characteristic 54.7° sidewall etch angle obtained via KOH etching of (1 0 0) orientation silicon wafers has been used to create a novel microneedle design. The KOH simultaneously etches both the front and back sides of the wafer to produce V shaped grooves, that intersect to form a sharp pyramidal six-sided microneedle tip. This method allows fabrication of solid microneedles with different geometries to determine the optimal microneedle length and width for effective penetration and minimally invasive drug delivery. A modified grooved microneedle design can also be used to create a hollow microneedle, via bonding of two grooved microneedles together, creating an enclosed hollow channel. The microneedle arrays developed, effectively penetrate the skin without significant indentation, thereby enabling effective delivery of active ingredients via either a poke and patch application using solid microneedles or direct injection using hollow microneedles. This simple, scalable and cost effective method utilises KOH to etch the silicon wafer in-plane, allowing microneedles with variable length of several mm to be fabricated, as opposed to out-of-plane MNs, which are geometrically restricted to dimensions less than the thickness of the wafer. These microneedle arrays have been used to demonstrate effective delivery of insulin and hyaluronic acid into the skin

A diastrophic dysplasia sulfate transporter (SLC26A2) mutant mouse: morphological and biochemical characterization of the resulting chondrodysplasia phenotype.

Mutations in the diastrophic dysplasia sulfate transporter (DTDST or SLC26A2) cause a family of recessively inherited chondrodysplasias including, in order of decreasing severity, achondrogenesis 1B, atelosteogenesis 2, diastrophic dysplasia (DTD) and recessive multiple epiphyseal dysplasia. The gene encodes a widely distributed sulfate/chloride antiporter of the cell membrane whose function is crucial for the uptake of inorganic sulfate, which is needed for proteoglycan sulfation. To provide new insights in the pathogenetic mechanisms leading to skeletal and connective tissue dysplasia and to obtain an in vivo model for therapeutic approaches to DTD, we generated a Dtdst knock-in mouse with a partial loss of function of the sulfate transporter. In addition, the intronic neomycine cassette in the mutant allele contributed to the hypomorphic phenotype by inducing abnormal splicing. Homozygous mutant mice were characterized by growth retardation, skeletal dysplasia and joint contractures, thereby recapitulating essential aspects of the DTD phenotype in man. The skeletal phenotype included reduced toluidine blue staining of cartilage, chondrocytes of irregular size, delay in the formation of the secondary ossification center and osteoporosis of long bones. Impaired sulfate uptake was demonstrated in chondrocytes, osteoblasts and fibroblasts. In spite of the generalized nature of the sulfate uptake defect, significant proteoglycan undersulfation was detected only in cartilage. Chondrocyte proliferation and apoptosis studies suggested that reduced proliferation and/or lack of terminal chondrocyte differentiation might contribute to reduced bone growth. The similarity with human DTD makes this mouse strain a useful model to explore pathogenetic and therapeutic aspects of DTDST-related disorders

Human Factors Investigation in Maritime Incident Analysis for Improved Ship Safety: an Innovative Approach Based on System Theory

The complexity of Human Factors interactions with ship safety will be addressed within the field of maritime accident analysis by means of the Causal Analysis using System Theory (CAST). This is a specific tool within the more comprehensive System-Theoretic Accident Model and Processes (STAMP) approach, already applied in other fields like aviation, defence, healthcare with significant outcomes in terms of safety enhancements. CAST can provide a framework to understand the entire accident process and identify the most important systemic causal factors, including the systemic socio-technical ones, since it provides the capability to spot weakness in existing safety control structure in order to possibly implement advances. In this perspective, the application to the Herald of Free Enterprise accident will be discussed, with focus on CAST effectiveness in assessing the complex Human Factors interaction with the ship safety control structure and in providing input to continuously enhance the ship safety and the ship resilience by design

APPLICATION OF CAST to COSTA CONCORDIA ACCIDENT

CAST (Causal Analysis based on Systems Theory) is used to rationally elicit the cause of Costa Concordia accident

HUMAN FACTOR AND AUTOMATION: A STPA APPRACH TO ENHANCE SHIP SAFETY

Ships complexity is continuously increasing and lots of action controls, traditionally carried out by crew members, are now managed and executed by the on-board automation systems. The relation among humans and automation system shall be studied with specific attention to their mutual interface and interaction issues, in order to better pursue safety. The STAMP (System-Theoretic Accident Model and Processes)-based tool named STPA (System Theoretic Process Analysis) consists the following steps: identify system hazards; draw functional control structure; identify unsafe control actions (UCAs); identify accident scenarios; formulate decisions and recommendations. In this paper an approach to model the relations among human operator and automation, based on STPA, will be proposed. An application case will be developed considering a large passenger ship and the specific hazard of dead ship condition (energy black-out). In case of navigation close to the shore and heavy weather condition, this situation can rapidly evolve into a ship loss