1,015 research outputs found

    Beta-lactams and Fluoroquinolones Dose Optimization in Critically Ill Patients:To TDM or not to TDM

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    Beta-lactams and Fluoroquinolones Dose Optimization in Critically Ill Patients:To TDM or not to TDM

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    Exploiting similarities between secret and cover images for improved embedding efficiency and security in digital steganography

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    The rapid advancements in digital communication technology and huge increase in computer power have generated an exponential growth in the use of the Internet for various commercial, governmental and social interactions that involve transmission of a variety of complex data and multimedia objects. Securing the content of sensitive as well as personal transactions over open networks while ensuring the privacy of information has become essential but increasingly challenging. Therefore, information and multimedia security research area attracts more and more interest, and its scope of applications expands significantly. Communication security mechanisms have been investigated and developed to protect information privacy with Encryption and Steganography providing the two most obvious solutions. Encrypting a secret message transforms it to a noise-like data which is observable but meaningless, while Steganography conceals the very existence of secret information by hiding in mundane communication that does not attract unwelcome snooping. Digital steganography is concerned with using images, videos and audio signals as cover objects for hiding secret bit-streams. Suitability of media files for such purposes is due to the high degree of redundancy as well as being the most widely exchanged digital data. Over the last two decades, there has been a plethora of research that aim to develop new hiding schemes to overcome the variety of challenges relating to imperceptibility of the hidden secrets, payload capacity, efficiency of embedding and robustness against steganalysis attacks. Most existing techniques treat secrets as random bit-streams even when dealing with non-random signals such as images that may add to the toughness of the challenges.This thesis is devoted to investigate and develop steganography schemes for embedding secret images in image files. While many existing schemes have been developed to perform well with respect to one or more of the above objectives, we aim to achieve optimal performance in terms of all these objectives. We shall only be concerned with embedding secret images in the spatial domain of cover images. The main difficulty in addressing the different challenges stems from the fact that the act of embedding results in changing cover image pixel values that cannot be avoided, although these changes may not be easy to detect by the human eye. These pixel changes is a consequence of dissimilarity between the cover LSB plane and the secretimage bit-stream, and result in changes to the statistical parameters of stego-image bit-planes as well as to local image features. Steganalysis tools exploit these effects to model targeted as well as blind attacks. These challenges are usually dealt with by randomising the changes to the LSB, using different/multiple bit-planes to embed one or more secret bits using elaborate schemes, or embedding in certain regions that are noise-tolerant. Our innovative approach to deal with these challenges is first to develop some image procedures and models that result in increasing similarity between the cover image LSB plane and the secret image bit-stream. This will be achieved in two novel steps involving manipulation of both the secret image and the cover image, prior to embedding, that result a higher 0:1 ratio in both the secret bit-stream and the cover pixels‘ LSB plane. For the secret images, we exploit the fact that image pixel values are in general neither uniformly distributed, as is the case of random secrets, nor spatially stationary. We shall develop three secret image pre-processing algorithms to transform the secret image bit-stream for increased 0:1 ratio. Two of these are similar, but one in the spatial domain and the other in the Wavelet domain. In both cases, the most frequent pixels are mapped onto bytes with more 0s. The third method, process blocks by subtracting their means from their pixel values and hence reducing the require number of bits to represent these blocks. In other words, this third algorithm also reduces the length of the secret image bit-stream without loss of information. We shall demonstrate that these algorithms yield a significant increase in the secret image bit-stream 0:1 ratio, the one that based on the Wavelet domain is the best-performing with 80% ratio.For the cover images, we exploit the fact that pixel value decomposition schemes, based on Fibonacci or other defining sequences that differ from the usual binary scheme, expand the number of bit-planes and thereby may help increase the 0:1 ratio in cover image LSB plane. We investigate some such existing techniques and demonstrate that these schemes indeed lead to increased 0:1 ratio in the corresponding cover image LSB plane. We also develop a new extension of the binary decomposition scheme that is the best-performing one with 77% ratio. We exploit the above two steps strategy to propose a bit-plane(s) mapping embedding technique, instead of bit-plane(s) replacement to make each cover pixel usable for secret embedding. This is motivated by the observation that non-binary pixel decomposition schemes also result in decreasing the number of possible patterns for the three first bit-planes to 4 or 5 instead of 8. We shall demonstrate that the combination of the mapping-based embedding scheme and the two steps strategy produces stego-images that have minimal distortion, i.e. reducing the number of the cover pixels changes after message embedding and increasing embedding efficiency. We shall also demonstrate that these schemes result in reasonable stego-image quality and are robust against all the targeted steganalysis tools but not against the blind SRM tool. We shall finally identify possible future work to achieve robustness against SRM at some payload rates and further improve stego-image quality

    A Comparison of the Human Umbilical Cord's Histomorphometric and Histological Structure in Pregnant Diabetic and Non-Diabetic Women

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    This study aimed to explore the histomorphometrical and histopathological alterations of umbilical cord (UC) vessels caused by gestational diabetes mellitus (GDM) and pre-gestational diabetes mellitus (PGDM). A total of thirty UC samples were obtained from full term pregnant women without any complications. Ten out of thirty UCs were obtained from non-diabetic pregnant women (normal group), 10 from GDM and 10 from PGDM pregnant women. Segments from the placental attachment, center and fetal side of UCs were taken for each group. These segments were processed for paraffin blocks, sectioned, and stained with H&E, Masson trichrome (MT) and Periodic Acid Shift (PAS). The results of the histomorphometric study showed no significant differences in the UC mean weight among these three groups. In three different segments, GDM resulted in a significant decrease in artery and vein wall thickness compared to the control group. GDM and PGDM resulted in a non-significant difference in the diameter of artery and vein in fetal segment, the vein in placental segment, and artery in the central segment compared with normal. All the UCs in the three groups contained two arteries and one vein but only one cord recorded in the GDM group contained one artery and one vein. Histological study of diabetic UC segments showed extravasation of blood, artery discordance, degeneration of Warton’s jelly (WJ) fibers with formation of honeycomb like empty spaces, formation of multiple spaces between smooth muscle cells of tunica media and detachment of the umbilical arteries from surrounding WJ. In both diabetic groups, there was a marked decrease in collagen fibers in tunica intima and media with their irregular arrangement in both arteries and vein especially in placental segment. The results also showed there was a rich carbohydrate content in the intima and media in all three groups. In conclusion, the current results proved that GDM and PGDM have an adverse effect on the structure of UC and its vessels. Keywords: Umbilical cord; Diabetes mellitus; Histological study; Special stains; Blood vessels DOI: 10.7176/JBAH/13-6-04 Publication date: April 30th 2023

    Stability of 10 Beta-Lactam Antibiotics in Human Plasma at Different Storage Conditions

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    BACKGROUND: Recently, several studies have assessed the effects of therapeutic drug monitoring of frequently prescribed beta-lactam antibiotics, for which they were quantified in human plasma samples. Beta-lactams are considered unstable, leading to extra challenges in quantification. Therefore, to ensure sample stability and minimize sample degradation before analysis, stability studies are crucial. This study investigated the stability of 10 frequently used beta-lactam antibiotics in human plasma at relevant storage conditions for clinical use. METHODS: Amoxicillin, benzylpenicillin, cefotaxime, ceftazidime, ceftriaxone, cefuroxime, flucloxacillin, imipenem, meropenem, and piperacillin were analyzed using ultraperformance convergence chromatography tandem mass spectrometry and liquid chromatography tandem mass spectrometry. Their short-term and long-term stabilities were investigated by measuring quality control samples at low and high concentrations against freshly prepared calibration standards. Measured concentrations at each time point were compared with the concentrations at T = 0. Antibiotics were considered stable if recovery results were between 85% and 115%. RESULTS: Short-term stability results indicated ceftriaxone, cefuroxime, and meropenem to be stable up to 24 hours at room temperature. All evaluated antibiotics, except imipenem, were stable on ice in a cool box for 24 hours. Amoxicillin, benzylpenicillin, and piperacillin were stable for 24 hours at 4-6°C. Cefotaxime, ceftazidime, cefuroxime, and meropenem were stable at 4-6°C up to 72 hours. Ceftriaxone and flucloxacillin were stable for 1 week at 4-6°C. Long-term stability results showed that all antibiotics were stable up to 1 year at -80°C, except imipenem and piperacillin, which were stable for 6 months at -80°C. CONCLUSIONS: Plasma samples for amoxicillin, benzylpenicillin, cefotaxime, ceftazidime, flucloxacillin, and piperacillin may be stored for a maximum of 24 hours in a cool box. Refrigeration is suitable for plasma samples of amoxicillin, benzylpenicillin, meropenem, and piperacillin for up to 24 hours and cefotaxime, ceftriaxone, ceftazidime and cefuroxime for 72 hours. Plasma samples for imipenem should be frozen directly at -80°C. For long-term storage, plasma samples can be stored at -80°C for a maximum of 6 months for imipenem and piperacillin and 12 months for all other evaluated antibiotics.</p

    The Pharmacokinetics of Beta-Lactam Antibiotics Using Scavenged Samples in Pediatric Intensive Care Patients:The EXPAT Kids Study Protocol

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    Background: Emerging evidence supports the importance of optimized antibiotic exposure in pediatric intensive care unit (PICU) patients. Traditional antibiotic dosing is not designed for PICU patients, as the extreme pharmacokinetic (PK) behavior of drugs threatens the achievement of optimal antibiotic treatment outcomes. Scavenged sampling is a sampling strategy which may have positive implications for routine TDM and PK research, as well as monitoring other biomarkers. EXPAT Kids study was designed to analyze whether current empiric dosing regimens of frequently used beta-lactam antibiotics achieve defined therapeutic target concentrations in PICU patients. Methods: A mono-centre, exploratory pharmacokinetic and pharmacodynamic study was designed to assess target attainment of beta-lactam antibiotics. One hundred forty patients will be included within 24 months after start of inclusion. At various time points serum concentration of the study antibiotic (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, flucloxacillin, and meropenem) are determined. In parallel with these sampling moments, residual material is collected to validate the use of blood of scavenged heparinized astrup syringes for the quantification of antibiotic exposure. The primary outcome is the time that the free (unbound) concentration of the study antibiotic remains above one to four the minimal inhibitory concentration during a dosing interval (100%ƒT > MIC and 100%ƒT>4xMIC). Other included outcomes are disease severity, safety, length of stay, and inflammatory biomarkers. Discussion: Potentially, scavenged sampling may enrich the EXPAT Kids dataset, and reduce additional blood sampling and workload for clinical personnel. The findings from the EXPAT Kids study will lead to new insights in the PK parameters of beta-lactams and consecutive effects on target attainment and clinical outcomes. Is there a need for more precision in dosing? Netherlands Trial Register Number: Trial NL9326

    Which patients benefit from model-informed precision dosing of beta-lactam antibiotics and ciprofloxacin at the ICU?

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    Objectives: Antibiotic dosing is not optimal in the ICU. Our recent trial investigated the effect of model-informed precision dosing (MIPD) of beta-lactam antibiotics and ciprofloxacin and showed no significant differences in clinical outcomes in all patients. This study aimed to identify subgroups of patients in which the MIPD of these antibiotics could be beneficial for clinical outcomes. Methods: We analysed data from the DOLPHIN randomized controlled trial, which compared MIPD to standard dosing of beta-lactam antibiotics and ciprofloxacin in 388 ICU patients. We divided patients into subgroups based on baseline characteristics and assessed the effect of MIPD on 28-day mortality, 6-month mortality, change in sequential organ failure assessment (delta-SOFA), and ICU length of stay (LOS). Results: We found a lower 28-day mortality in patients with a SOFA below 8 randomized to MIPD (OR 0.40; 95% CI 0.17–0.88). However, patients with a higher SOFA show an increased 28-day mortality (OR 1.94; 95% CI 1.07–3.59) in the MIPD group. ICU LOS was increased in patients receiving MIPD with a SOFA below 8 (IRR 1.36; 95% CI 1.01–1.83) and those receiving MIPD for ceftriaxone (IRR 1.76; 95% CI 1.24–2.51). Patients receiving a dose recommendation within 24 hours show a trend towards decreased ICU LOS (IRR 0.77; 95% CI 0.52–1.16) and higher delta-SOFA (estimate -1.19; 95% CI -2.98–0.60). Conclusions: ICU patients with a SOFA below 8 using MIPD had an increased ICU LOS but a lower 28-day mortality. Fast dose recommendations using MIPD of beta-lactam antibiotics and ciprofloxacin needs to be investigated in ICU patients.</p
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