This article presents the concrete benefits of applying a model-based systems engineering approach using selected examples in the life cycle of Wendelstein 7-X.
A safety instrumented system (SIS) is in place for the continuous safe operation of Wendelstein 7-X (W7-X). The central safety system (cSS) is part of this system. Prior to the last operation phase ...(OP) 2.1 in preparation for the steady-state regime, the cSS was fundamentally revised. A requirements engineering tool (RET) was introduced to support the development process. The SIS development plan, adapted to the W7-X, provides for fixed steps. All functional requirements derived from the W7-X risk analysis for the cSS and derived objects along the safety lifecycle are documented in the RET by means of work items. In this way, the requirements of the SIS standards and those of the approving authorities can be met. Dependency relationships have been established between the work items to allow the analysis of completeness, dependency, and explicitness, as well as the analysis of the impact of possible changes at any point in the process. The requests for adaptations and extensions to the cSS, derived from the experience with the SIS in OP2.1, are also organized with the RET.
Techniques to treat urethral stricture and hypospadias are restricted, as substitution of the unhealthy urethra with tissue from other origins (skin, bladder or buccal mucosa) has some limitations. ...Therefore, alternative sources of tissue for use in urethral reconstructions are considered, such as ex vivo engineered constructs.
To review recent literature on tissue engineering for human urethral reconstruction.
A search was made in the PubMed and Embase databases restricted to the last 25 years and the English language.
A total of 45 articles were selected describing the use of tissue engineering in urethral reconstruction. The results are discussed in four groups: autologous cell cultures, matrices/scaffolds, cell-seeded scaffolds, and clinical results of urethral reconstructions using these materials. Different progenitor cells were used, isolated from either urine or adipose tissue, but slightly better results were obtained with in vitro expansion of urothelial cells from bladder washings, tissue biopsies from the bladder (urothelium) or the oral cavity (buccal mucosa). Compared with a synthetic scaffold, a biological scaffold has the advantage of bioactive extracellular matrix proteins on its surface. When applied clinically, a non-seeded matrix only seems suited for use as an onlay graft. When a tubularized substitution is the aim, a cell-seeded construct seems more beneficial.
Considerable experience is available with tissue engineering of urethral tissue in vitro, produced with cells of different origin. Clinical and in vivo experiments show promising results.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVES:Early identification of potential recovery of postanoxic coma is a major challenge. We studied the additional predictive value of EEG.
METHODS:Two hundred seventy-seven consecutive ...comatose patients after cardiac arrest were included in a prospective cohort study on 2 intensive care units. Continuous EEG was measured during the first 3 days. EEGs were classified as unfavorable (isoelectric, low-voltage, burst-suppression with identical bursts), intermediate, or favorable (continuous patterns), at 12, 24, 48, and 72 hours. Outcome was dichotomized as good or poor. Resuscitation, demographic, clinical, somatosensory evoked potential, and EEG measures were related to outcome at 6 months using logistic regression analysis. Analyses of diagnostic accuracy included receiver operating characteristics and calculation of predictive values.
RESULTS:Poor outcome occurred in 149 patients (54%). Single measures unequivocally predicting poor outcome were an unfavorable EEG pattern at 24 hours, absent pupillary light responses at 48 hours, and absent somatosensory evoked potentials at 72 hours. Together, these had a specificity of 100% and a sensitivity of 50%. For the remaining 203 patients, who were still in the “gray zone” at 72 hours, a predictive model including unfavorable EEG patterns at 12 hours, absent or extensor motor response to pain at 72 hours, and higher age had an area under the curve of 0.90 (95% confidence interval 0.84–0.96). Favorable EEG patterns at 12 hours were strongly associated with good outcome. EEG beyond 24 hours had no additional predictive value.
CONCLUSIONS:EEG within 24 hours is a robust contributor to prediction of poor or good outcome of comatose patients after cardiac arrest.
The Wendelstein 7-X (W7-X) optimized stellarator fusion experiment, which went into operation in 2015, has been operating since 2017 with an un-cooled modular graphite divertor. This allowed first ...divertor physics studies to be performed at pulse energies up to 80 MJ, as opposed to 4 MJ in the first operation phase, where five inboard limiters were installed instead of a divertor. This, and a number of other upgrades to the device capabilities, allowed extension into regimes of higher plasma density, heating power, and performance overall, e.g. setting a new stellarator world record triple product. The paper focuses on the first physics studies of how the island divertor works. The plasma heat loads arrive to a very high degree on the divertor plates, with only minor heat loads seen on other components, in particular baffle structures built in to aid neutral compression. The strike line shapes and locations change significantly from one magnetic configuration to another, in very much the same way that codes had predicted they would. Strike-line widths are as large as 10 cm, and the wetted areas also large, up to about 1.5 m2, which bodes well for future operation phases. Peak local heat loads onto the divertor were in general benign and project below the 10 MW m−2 limit of the future water-cooled divertor when operated with 10 MW of heating power, with the exception of low-density attached operation in the high-iota configuration. The most notable result was the complete (in all 10 divertor units) heat-flux detachment obtained at high-density operation in hydrogen.
Wendelstein 7-X (W7-X) is currently under commissioning in preparation for its initial plasma operation phase, operation phase 1.1 (OP1.1). This first phase serves primarily to provide an integral ...commissioning of all major systems needed for plasma operation, as well as systems, such as diagnostics, that need plasma operation to verify their foreseen functions. In OP1.1, W7-X will have a reduced set of in-vessel components. In particular, five graphite limiter stripes replace the later foreseen divertor. This paper describes the expected machine capabilities in OP1.1, as well as a selection of physics topics that can be addressed in OP1.1, despite the simplified configuration and the reduced machine capabilities. Physics topics include the verification and adjustment of the magnetic topology, the testing of the foreseen plasma start-up scenarios and the feed-forward control of plasma density and temperature evolution, as well as more advanced topics such as scrape-off layer (SOL) studies at short connection lengths and transport studies. Plasma operation in OP1.1 will primarily be performed in helium, with a hydrogen plasma phase at the end.
Summary
Osteoarthritis (OA) is the most common joint disease that strongly reduces the quality of life in patients; However, no disease‐modifying therapy is available. For a long time, OA was ...considered a non‐inflammatory disease that was the result of ‘wear‐and‐tear’ and abnormal mechanics, and therefore many considered the term ‘osteoarthritis’ a misnomer. However, during the last decades the notion arose that inflammation is not only present in the majority of OA patients but, rather, actively involved in the progression of the disease. Influx of immune cells is observed in the synovium and a plethora of inflammatory mediators is present in tissues and fluids from OA patients. These mediators cause the production of degrading enzymes that break down the cartilage matrix, which is the main hallmark of OA. Alarmins, which belong to the group of danger signals, have been implicated in many inflammatory diseases. They are among the first factors to be released upon cell stress due to, for example, infection, damage and inflammation. They attract and activate cells of the immune system and therefore lie at the base of the inflammatory reaction. In this narrative review, an overview of the history of OA, the evolving concept of inflammation as important factor in the OA pathogenesis, and particularly the central role that alarmins play in the initiation and maintenance of the low‐grade inflammatory response in OA, is provided. Moreover, the targeting of alarmins as a promising approach to dampen the inflammation in OA is highlighted.
Whereas osteoarthritis was historically considered a disease solely of the articular cartilage, it is nowadays broadly accepted that inflammation plays a crucial role in the disease development. Of particular interest in the inflammatory cascade during osteoarthritis are the alarmins, which are released upon cell stress and lie at the basis of the immune reaction. This review gives an overview of the inflammatory processes that are involved in osteoarthritis, with a particular focus on alarmins, and provides possibilities to inhibit these alarmins.
An extended modification phase of the superconducting fusion experiment Wendelstein 7-X (W7-X) was completed late 2021 after installing actively cooled divertor units and the integration or ...modification of new technical components and diagnostics. Currently, the commissioning of the W7-X experiment is underway. First, technical plasma operation is scheduled for the end of September 2022, and scientific plasma operation will start at the end of November. The fast interlock system (FIS) is an important component of the safety instrumented system (SIS) of W7-X. The main task of the FIS is to protect the inner plasma vessel components from thermal overload from both plasma heating systems (e.g., neutral beam injection) and the plasma itself. There are strict limits for reaction times after detection of interlock relevant events, which have to be observed in order to prevent overload situations of the first wall. The requirements for the FIS were substantially modified and extended, in order to address the challenges due to the actively cooled divertor. This led to extensive revision of the technical implementation and the software of the FIS. In this article, after a short introduction of FIS design and operation in operating phase (OP1), the modification of FIS for OP 2.1 operation is presented. Finally, the first results during the OP 2.1 commissioning and operation of the FIS are discussed.
Performing exhaustive searches over a large number of text documents can be tedious, since it is very hard to formulate search queries or define filter criteria that capture an analyst's information ...need adequately. Classification through machine learning has the potential to improve search and filter tasks encompassing either complex or very specific information needs, individually. Unfortunately, analysts who are knowledgeable in their field are typically not machine learning specialists. Most classification methods, however, require a certain expertise regarding their parametrization to achieve good results. Supervised machine learning algorithms, in contrast, rely on labeled data, which can be provided by analysts. However, the effort for labeling can be very high, which shifts the problem from composing complex queries or defining accurate filters to another laborious task, in addition to the need for judging the trained classifier's quality. We therefore compare three approaches for interactive classifier training in a user study. All of the approaches are potential candidates for the integration into a larger retrieval system. They incorporate active learning to various degrees in order to reduce the labeling effort as well as to increase effectiveness. Two of them encompass interactive visualization for letting users explore the status of the classifier in context of the labeled documents, as well as for judging the quality of the classifier in iterative feedback loops. We see our work as a step towards introducing user controlled classification methods in addition to text search and filtering for increasing recall in analytics scenarios involving large corpora.
Objective:
This study was designed to establish the reliability of neurologic examination, neuron‐specific enolase (NSE), and median nerve somatosensory‐evoked potentials (SEPs) to predict poor ...outcome in patients treated with mild hypothermia after cardiopulmonary resuscitation (CPR).
Methods:
This multicenter prospective cohort study included adult comatose patients admitted to the intensive care unit (ICU) after CPR and treated with hypothermia (32–34°C). False‐positive rates (FPRs 1 − specificity) with their 95% confidence intervals (CIs) were calculated for pupillary light responses, corneal reflexes, and motor scores 72 hours after CPR; NSE levels at admission, 12 hours after reaching target temperature, and 36 hours and 48 hours after collapse; and SEPs during hypothermia and after rewarming. The primary outcome was poor outcome, defined as death, vegetative state, or severe disability (Glasgow Outcome Scale 1–3) after 6 months.
Results:
Of 391 patients included, 53% had a poor outcome. Absent pupillary light responses (FPR 1; 95% CI, 0–7) or absent corneal reflexes (FPR 4; 95% CI, 1–13) 72 hours after CPR, and absent SEPs during hypothermia (FPR 3; 95% CI, 1–7) and after rewarming (FPR 0; 95% CI, 0–18) were reliable predictors. Motor scores 72 hours after CPR (FPR 10; 95% CI, 6–16) and NSE levels were not.
Interpretation:
In patients with persisting coma after CPR and therapeutic hypothermia, use of motor score or NSE, as recommended in current guidelines, could possibly lead to inappropriate withdrawal of treatment. Poor outcomes can reliably be predicted by testing brainstem reflexes 72 hours after CPR and performing SEP. ANN NEUROL 2012;71:206–212
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