Simulation of Automated File Migratoon in Information Lifecycle Management

Information Lifecycle Management (ILM) is a strategic concept for storage of information and documents. ILM is based on the idea that in an enterprise information have different values. Information with different values are stored on different storage hierarchies. ILM offers significant potential cost savings by tiering storage and 90% of decision makers consider implementing ILM (Linden 2006). Nonetheless, there are too few experience reports and experimenting and researching in real systems are too expensive. This paper addresses this issue and contributes to supporting and assisting IT managers in their decision-making process. ILM automation needs migration rules. There are well-known static, heuristic migration rules and we present a new dynamic migration rule for ILM. These migration rules are implemented in an ILM simulator. We compare the performance of the new dynamic rule with the heuristics. The simulative approach has two advantages. On the one hand it offers predictions about the dynamic behaviour of an ILM migration rule and, on the other hand, it dispenses with real storage hardware. Simulation leads to decisions under certainty. When making a decision under certainty, the major problem is to determine which is the trade-off among different objectives. Cost-benefit analysis can be used to this purpose. A decision matrix is laid where rows represent choices and columns represent states of nature. The simulated results support the choice of migration rules and help to avoid mismanagement and poor investments in advance. The results raise the awareness of choosing the best alternative

Microimaging of a novel intracochlear drug delivery device in combination with cochlear implants in the human inner ear

The effective delivery of drugs to the inner ear is still an unmet medical need. Local controlled drug delivery to this sensory organ is challenging due to its location in the petrous bone, small volume, tight barriers, and high vulnerability. Local intracochlear delivery of drugs would overcome the limitations of intratympanic (extracochlear) and systemic drug application. The requirements for such a delivery system include small size, appropriate flexibility, and biodegradability. We have developed biodegradable PLGA-based implants for controlled intracochlear drug release that can also be used in combination with cochlear implants (CIs), which are implantable neurosensory prosthesis for hearing rehabilitation. The drug carrier system was tested for implantation in the human inner ear in 11 human temporal bones. In five of the temporal bones, CI arrays from different manufacturers were implanted before insertion of the biodegradable PLGA implants. The drug carrier system and CI arrays were implanted into the scala tympani through the round window. Implanted temporal bones were evaluated by ultra-high-resolution computed tomography (µ-CT) to illustrate the position of implanted electrode carriers and the drug carrier system. The µ-CT measurements revealed the feasibility of implanting the PLGA implants into the scala tympani of the human inner ear and co-administration of the biodegradable PLGA implant with a CI array

Intratympanic corticosteroids for sudden sensorineural hearing loss

BACKGROUND: Idiopathic sudden sensorineural hearing loss (ISSNHL) is common, and defined as a sudden decrease in sensorineural hearing sensitivity of unknown aetiology. Systemic corticosteroids are widely used, however their value remains unclear. Intratympanic injections of corticosteroids have become increasingly common in the treatment of ISSNHL. OBJECTIVES: To assess the effects of intratympanic corticosteroids in people with ISSNHL. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; CENTRAL (2021, Issue 9); PubMed; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials (search date 23 September 2021). SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving people with ISSNHL and follow-up of over a week. Intratympanic corticosteroids were given as primary or secondary treatment (after failure of systemic therapy). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods, including GRADE to assess the certainty of the evidence. Our primary outcome was change in hearing threshold with pure tone audiometry. Secondary outcomes included the proportion of people whose hearing improved, final hearing threshold, speech audiometry, frequency-specific hearing changes and adverse effects. MAIN RESULTS: We included 30 studies, comprising 2133 analysed participants. Some studies had more than two treatment arms and were therefore relevant to several comparisons. Studies investigated intratympanic corticosteroids as either primary (initial) therapy or secondary (rescue) therapy after failure of initial treatment. 1. Intratympanic corticosteroids versus systemic corticosteroids as primary therapy We identified 16 studies (1108 participants). Intratympanic therapy may result in little to no improvement in the change in hearing threshold (mean difference (MD) -5.93 dB better, 95% confidence interval (CI) -7.61 to -4.26; 10 studies; 701 participants; low-certainty). We found little to no difference in the proportion of participants whose hearing was improved (risk ratio (RR) 1.04, 95% CI 0.97 to 1.12; 14 studies; 972 participants; moderate-certainty). Intratympanic therapy may result in little to no difference in the final hearing threshold (MD -3.31 dB, 95% CI -6.16 to -0.47; 7 studies; 516 participants; low-certainty). Intratympanic therapy may increase the number of people who experience vertigo or dizziness (RR 2.53, 95% CI 1.41 to 4.54; 1 study; 250 participants; low-certainty) and probably increases the number of people with ear pain (RR 15.68, 95% CI 6.22 to 39.49; 2 studies; 289 participants; moderate-certainty). It also resulted in persistent tympanic membrane perforation (range 0% to 3.9%; 3 studies; 359 participants; very low-certainty), vertigo/dizziness at the time of injection (1% to 21%, 3 studies; 197 participants; very low-certainty) and ear pain at the time of injection (10.5% to 27.1%; 2 studies; 289 participants; low-certainty). 2. Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as primary therapy We identified 10 studies (788 participants). Combined therapy may have a small effect on the change in hearing threshold (MD -8.55 dB better, 95% CI -12.48 to -4.61; 6 studies; 435 participants; low-certainty). The evidence is very uncertain as to whether combined therapy changes the proportion of participants whose hearing is improved (RR 1.27, 95% CI 1.15 to 1.41; 10 studies; 788 participants; very low-certainty). Combined therapy may result in slightly lower (more favourable) final hearing thresholds but the evidence is very uncertain, and it is not clear whether the change would be important to patients (MD -9.11 dB, 95% CI -16.56 to -1.67; 3 studies; 194 participants; very low-certainty). Some adverse effects only occurred in those who received combined therapy. These included persistent tympanic membrane perforation (range 0% to 5.5%; 5 studies; 474 participants; very low-certainty), vertigo or dizziness at the time of injection (range 0% to 8.1%; 4 studies; 341 participants; very low-certainty) and ear pain at the time of injection (13.5%; 1 study; 73 participants; very low-certainty).  3. Intratympanic corticosteroids versus no treatment or placebo as secondary therapy We identified seven studies (279 participants). Intratympanic therapy may have a small effect on the change in hearing threshold (MD -9.07 dB better, 95% CI -11.47 to -6.66; 7 studies; 280 participants; low-certainty). Intratympanic therapy may result in a much higher proportion of participants whose hearing is improved (RR 5.55, 95% CI 2.89 to 10.68; 6 studies; 232 participants; low-certainty). Intratympanic therapy may result in lower (more favourable) final hearing thresholds (MD -11.09 dB, 95% CI -17.46 to -4.72; 5 studies; 203 participants; low-certainty). Some adverse effects only occurred in those who received intratympanic injection. These included persistent tympanic membrane perforation (range 0% to 4.2%; 5 studies; 185 participants; very low-certainty), vertigo or dizziness at the time of injection (range 6.7% to 33%; 3 studies; 128 participants; very low-certainty) and ear pain at the time of injection (0%; 1 study; 44 participants; very low-certainty).  4. Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as secondary therapy We identified one study with 76 participants. Change in hearing threshold was not reported. Combined therapy may result in a higher proportion with hearing improvement, but the evidence is very uncertain (RR 2.24, 95% CI 1.10 to 4.55; very low-certainty). Adverse effects were poorly reported with only data for persistent tympanic membrane perforation (rate 8.1%, very low-certainty). AUTHORS' CONCLUSIONS: Most of the evidence in this review is low- or very low-certainty, therefore it is likely that further studies may change our conclusions.   For primary therapy, intratympanic corticosteroids may have little or no effect compared with systemic corticosteroids. There may be a slight benefit from combined treatment when compared with systemic treatment alone, but the evidence is uncertain. For secondary therapy, there is low-certainty evidence that intratympanic corticosteroids, when compared to no treatment or placebo, may result in a much higher proportion of participants whose hearing is improved, but may only have a small effect on the change in hearing threshold. It is very uncertain whether there is additional benefit from combined treatment over systemic steroids alone. Although adverse effects were poorly reported, the different risk profiles of intratympanic treatment (including tympanic membrane perforation, pain and dizziness/vertigo) and systemic treatment (for example, blood glucose problems) should be considered when selecting appropriate treatment

Primary URECs: a source to better understand the pathology of renal tubular epithelia in pediatric hereditary cystic kidney diseases

Background In pediatric hereditary cystic kidney diseases, epithelial cell defects mostly result from rare, autosomal recessively inherited pathogenic variants in genes encoding proteins of the cilia-centrosome complex. Consequences of individual gene variants on epithelial function are often difficult to predict and can furthermore depend on the patient's genetic background. Here, we studied urine-derived renal tubular epithelial cells (URECs) from genetically determined, pediatric cohorts of different hereditary cystic kidney diseases, comprising autosomal recessive polycystic kidney disease, nephronophthisis (NPH) and the Bardet Biedl syndrome (BBS). UREC characteristics and behavior in epithelial function-related 3D cell culture were compared in order to identify gene and variant-specific properties and to determine aspects of epithelial (cell) dysfunction. Results UREC preparations from patients (19) and healthy controls (39) were studied in a qualitative and quantitative manner using primary cells cultured for up-to 21 days. In patients with biallelic pathogenic variants in PKHD1 or NPHP genes, we were able to receive satisfactory amounts of URECs of reproducible quality. In BBS patients, UREC yield was lower and more dependent on the individual genotype. In contrast, in UREC preparations derived from healthy controls, no predictable and satisfactory outcome could be established. Considering cell proliferation, tubular origin and epithelial properties in 2D/3D culture conditions, we observed distinct and reproducible epithelial properties of URECs. In particular, the cells from patients carrying PKHD1 variants were characterized by a high incidence of defective morphogenesis of monolayered spheroids-a property proposed to be suitable for corrective intervention. Furthermore, we explored different ways to generate reference cell lines for both-patients and healthy controls-in order to eliminate restrictions in cell number and availability of primary URECs. Conclusions Ex vivo 3D cell culture of primary URECs represents a valuable, non-invasive source to evaluate epithelial cell function in kidney diseases and as such helps to elucidate the functional consequences of rare genetic disorders. In combination with genetically defined control cell lines to be generated in the future, the cultivation of primary URECs could become a relevant tool for testing personalized treatment of epithelial dysfunction in patients with hereditary cystic kidney disease

Hypo-fractionated SBRT for localized prostate cancer: a German bi-center single treatment group feasibility trial

Abstract Background For prostate cancer treatment, treatment options with minimal side effects are desired. External beam radiation therapy (EBRT) is non-invasive, standard of care and delivered in either conventional fractionation over 8 weeks or with moderate hypo-fractionation over about 5 weeks. Recent advances in radiotherapy technology have made extreme hypo-fractionated stereotactic body radiation therapy (SBRT) of prostate cancer feasible, which has not yet been introduced as a standard treatment method in Germany. Initial results from other countries are promising, but long-term results are not yet available. The aim of this study is to investigate feasibility and effectiveness of SBRT for prostate cancer in Germany. Methods/design This German bi-center single group trial (HYPOSTAT) is designed to evaluate feasibility and effectiveness, as measured by toxicity and PSA-response, respectively, of an extreme hypo-fractionated SBRT regimen with five fractions of 7 Gy in treatment of localized low and intermediate risk prostate cancer. The target volume includes the prostate with or without the base of seminal vesicles depending on risk stratification and uncertainty margins that are kept at 3–5 mm. SBRT treatment is delivered with the robotic CyberKnife system, which was recently introduced in Germany. Acute and late toxicity after one year will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE v. 4.0), Radiation Therapy Oncology Group (RTOG) and International Prostate Symptom Score (IPSS) Scores. The quality of life will be assessed before and after treatment with the EORTC QLQ C30 questionnaire. Hypothesizing that the proportion of patients with grade 2 side effects or higher is less or equal than 2.8%, thus markedly lower than the standard EBRT percentage (17.5%), the recruitment target is 85 patients. Discussion The HYPOSTAT trial aims at demonstrating short term feasibility of extreme hypo-fractioned SBRT for the treatment of prostate cancer and might be used as the pilot study for a multi-center multi-platform or for randomized-controlled trials comparing conventional radiotherapy with SBRT for localized prostate cancer in the future. The study concept of patient enrollment, follow up and evaluation by multiple public university clinics and actual patient treatment in dedicated private radiosurgery practices with high-tech radiation equipment is unique for clinical trials. Study status The study is ongoing and currently recruiting patients. Trial registration Registration number: NCT02635256 ( clinicaltrials.gov ). Registered 8 December 2015

Anionic silicate organic frameworks constructed from hexacoordinate silicon centres

Crystalline frameworks composed of hexacoordinate silicon species have thus far only been observed in a few high pressure silicate phases. By implementing reversible Si-O chemistry for the crystallization of covalent organic frameworks, we demonstrate the simple one-pot synthesis of silicate organic frameworks based on octahedral dianionic SiO6 building units. Clear evidence of the hexacoordinate environment around the silicon atoms is given by Si-29 nuclear magnetic resonance analysis. Characterization by high-resolution powder X-ray diffraction, density functional theory calculation and analysis of the pair-distribution function showed that those anionic frameworks-M-2[Si(C16H10O4)(1.5)], where M = Li, Na, K and C16H10O4 is 9,10-dimethylanthracene-2,3,6,7-tetraolate-crystallize as two-dimensional hexagonal layers stabilized in a fully eclipsed stacking arrangement with pronounced disorder in the stacking direction. Permanent microporosity with high surface area (up to 1,276 m(2) g(-1)) was evidenced by gas-sorption measurements. The negatively charged backbone balanced with extra-framework cations and the permanent microporosity are characteristics that are shared with zeolites