Intraoperative Use of Epsilon Amino Caproic Acid and Tranexamic Acid in Surgeries Performed Under Cardiopulmonary Bypass: a Comparative Study To Assess Their Impact On Reopening Due To Postoperative Bleeding

BACKGROUND: Open heart surgeries under cardiopulmonary bypass are associated with excessive perioperative bleeding that often requires reoperation. Antifibrinolytics like epsilon aminocaproic acid and tranexamic acid are widely used to control bleeding. There are limited studies primarily showing the impact of these drugs on the incidence of reopening following open heart surgical procedures. The goal of this study was to compare incidence of reopening following open heart surgeries in patients who were administered either epsilon amino caproic acid or tranexamic acid for control of perioperative bleeding.METHODS: A prospective, randomized, controlled trial was performed among seventy-eight patients of either sex in the age group of 18 to 65 years scheduled for open heart surgeries under cardiopulmonary bypass. They were randomly allocated into three groups where group A (n=26) received epsilon aminocaproic acid, group B (n=26) received tranexamic acid and group C (control group, n=26) received intravenous 0.9% normal saline. Patients had similar anaesthetic protocols, and were monitored for twenty-four hours postoperatively to assess reopening rates because of excessive bleeding.RESULTS: Two patients in each group receiving either tranexamic acid or epsilon aminocaproic acid had excessive bleeding requiring reopening after surgery whereas three patients in the control group had undergone reopening for excessive bleeding (p>0.05).CONCLUSIONS: Epsilon aminocaproic acid and tranexamic acid exhibit similar and comparable effect to placebo on incidence of reopening for excessive bleeding following open heart surgeries under cardiopulmonary bypassKEYWORDS: Bleeding, CPB, CABG, antifibrinilytic

Inter-cluster Thread-to-core Mapping and DVFS on Heterogeneous Multi-cores

Heterogeneous multi-core platforms that contain different types of cores, organized as clusters, are emerging, e.g. ARM's big.LITTLE architecture. These platforms often need to deal with multiple applications, having different performance requirements, executing concurrently. This leads to generation of varying and mixed workloads (e.g. compute and memory intensive) due to resource sharing. Run-time management is required for adapting to such performance requirements and workload variabilities and to achieve energy efficiency. Moreover, the management becomes challenging when the applications are multi-threaded and the heterogeneity needs to be exploited. The existing run-time management approaches do not efficiently exploit cores situated in different clusters simultaneously (referred to as inter-cluster exploitation) and DVFS potential of cores, which is the aim of this paper. Such exploitation might help to satisfy the performance requirement while achieving energy savings at the same time. Therefore, in this paper, we propose a run-time management approach that first selects thread-to-core mapping based on the performance requirements and resource availability. Then, it applies online adaptation by adjusting the voltage-frequency (V-f) levels to achieve energy optimization, without trading-off application performance. For thread-to-core mapping, offline profiled results are used, which contain performance and energy characteristics of applications when executed on the heterogeneous platform by using different types of cores in various possible combinations. For an application, thread-to-core mapping process defines the number of used cores and their type, which are situated in different clusters. The online adaptation process classifies the inherent workload characteristics of concurrently executing applications, incurring a lower overhead than existing learning-based approaches as demonstrated in this paper. The classification of workload is performed using the metric Memory Reads Per Instruction (MRPI). The adaptation process pro-actively selects an appropriate V-f pair for a predicted workload. Subsequently, it monitors the workload prediction error and performance loss, quantified by instructions per second (IPS), and adjusts the chosen V-f to compensate. We validate the proposed run-time management approach on a hardware platform, the Odroid-XU3, with various combinations of multi-threaded applications from PARSEC and SPLASH benchmarks. Results show an average improvement in energy efficiency up to 33% compared to existing approaches while meeting the performance requirements

Microstructural evolution under low shear rates during Rheo processing of LM25 alloy

© ASM InternationalMicrostructural features of LM25 alloy processed by two different routes: (1) conventional casting, and(2)shear casting based on inclined heated surface are studied. The microstructures of the primary phase for the shear-cast samples show rosette or ellipsoidal morphologies. Heat transfer of contacting melt with the inclined tube surface and shear stress exerted on the layers of the melt as result of gravitational force are crucial parameters for the microstructural evolution. Compared to those produced by conventional casting, shear-cast samples have a much improved tensile strength and ductility due to globular microstructure

A literature review on surgery for cervical vagal schwannomas

Cervical vagal schwannoma is a benign, slow-growing mass, often asymptomatic, with a very low lifetime risk of malignant transformation in general population, but diagnosis is still a challenge. Surgical resection is the treatment of choice even if its close relationship with nerve fibres, from which it arises, threats vagal nerve preservation. We present a case report and a systematic review of literature. All studies on surgical resection of cervical vagal schwannoma have been reviewed. Papers matching the inclusion criteria (topic on surgical removal of cervical vagal schwannoma, English language, full text available) were selected. Fifty-three patients with vagal neck schwannoma submitted to surgery were identified among 22 studies selected. Female/male ratio was 1.5 and median age 44 years. Median diameter was 5 cm (range 2 to 10). Most schwannoma were asymptomatic (68.2%) and received an intracapsular excision (64.9%). Postoperative symptoms were reported in 22.6% of patients. Cervical vagal schwannoma is a benign pathology requiring surgical excision, but frequently postoperative complications can affect patients lifelong, so, surgical indications should be based carefully on the balance between risks and benefits

Quantifying the impact of immunotherapy on RNA dynamics in cancer

BACKGROUND: Checkpoint inhibitor (CPI) immunotherapies have provided durable clinical responses across a range of solid tumor types for some patients with cancer. Nonetheless, response rates to CPI vary greatly between cancer types. Resolving intratumor transcriptomic changes induced by CPI may improve our understanding of the mechanisms of sensitivity and resistance. METHODS: We assembled a cohort of longitudinal pre-therapy and on-therapy samples from 174 patients treated with CPI across six cancer types by leveraging transcriptomic sequencing data from five studies. RESULTS: Meta-analyses of published RNA markers revealed an on-therapy pattern of immune reinvigoration in patients with breast cancer, which was not discernible pre-therapy, providing biological insight into the impact of CPI on the breast cancer immune microenvironment. We identified 98 breast cancer-specific correlates of CPI response, including 13 genes which are known IO targets, such as toll-like receptors TLR1, TLR4, and TLR8, that could hold potential as combination targets for patients with breast cancer receiving CPI treatment. Furthermore, we demonstrate that a subset of response genes identified in breast cancer are already highly expressed pre-therapy in melanoma, and additionally we establish divergent RNA dynamics between breast cancer and melanoma following CPI treatment, which may suggest distinct immune microenvironments between the two cancer types. CONCLUSIONS: Overall, delineating longitudinal RNA dynamics following CPI therapy sheds light on the mechanisms underlying diverging response trajectories, and identifies putative targets for combination therapy

Performance, feed utilization, and hepatic metabolic response of weaned juvenile Atlantic bluefin tuna (Thunnus thynnus L.): effects of dietary lipid level and source

The development of formulated diets and feeds is essential to increase production of farmed tuna species. There is limited knowledge of this topic, mainly on Pacific Bluefin tuna (Thunnus orientalis) in Japan, whereas no major attempts have been made with Atlantic Bluefin tuna (Thunnus thynnus; ABT). In the present study, two trials were performed using inert formulated diets as on-growing feeds for weaned ABT juvenile in order to establish adequate dietary levels of both lipid and omega-3 long-chain polyunsaturated fatty acids (LC-PUFA). In a first trial, ABT (initial weight = 2.9±0.9g) were fed for 10 days with either a commercial (Magokoro®, MGK) or two experimental feeds with two different lipid levels (15 or 20%) using krill oil (KO) as the single lipid source in order to estimate the suitable lipid content. Fish fed MGK displayed the highest growth, followed by 15KO, with no differences in fish survival. Thus, a lipid content of 15% was considered better than 20% for ABT juveniles. In the second trial, fish (initial weight = 3.3 ± 0.6g) were fed either MGK, 15KO or a feed containing 15% lipid with a combination (1:1, v/v) KO and rapeseed oil (RO) (15KORO). Fish fed 15KO and 15KORO showed the highest growth in terms of weight and fork length (including weight gain and SGR). Increasing dietary lipid level or adding RO to the feeds did not increase liver lipid content. The liver fatty acid profile largely reflected dietary intake confirming very limited LC-PUFA biosynthetic activity for this teleost species. In this respect, liver of fish fed 15KO and 20KO displayed the highest contents of docosahexaenoic acid (DHA). The hepatic expression of genes of lipid and fatty acid metabolism, transcription factors, and antioxidant enzymes was investigated with many of the genes showing regulation by both dietary lipid and LC-PUFA contents. The present study showed promising results that suggested ABT juveniles can be on grown on inert dry feeds that supported good fish growth and the accumulation of the health-promoting fatty acid DHA. Further studies are required in order to fully elucidate lipid and fatty acid requirements of this iconic species regarding dietary sources and production costs.En prensa1,52

Hydroimidazolone Modification of the Conserved Arg12 in Small Heat Shock Proteins: Studies on the Structure and Chaperone Function Using Mutant Mimics

Methylglyoxal (MGO) is an α-dicarbonyl compound present ubiquitously in the human body. MGO reacts with arginine residues in proteins and forms adducts such as hydroimidazolone and argpyrimidine in vivo. Previously, we showed that MGO-mediated modification of αA-crystallin increased its chaperone function. We identified MGO-modified arginine residues in αA-crystallin and found that replacing such arginine residues with alanine residues mimicked the effects of MGO on the chaperone function. Arginine 12 (R12) is a conserved amino acid residue in Hsp27 as well as αA- and αB-crystallin. When treated with MGO at or near physiological concentrations (2–10 µM), R12 was modified to hydroimidazolone in all three small heat shock proteins. In this study, we determined the effect of arginine substitution with alanine at position 12 (R12A to mimic MGO modification) on the structure and chaperone function of these proteins. Among the three proteins, the R12A mutation improved the chaperone function of only αA-crystallin. This enhancement in the chaperone function was accompanied by subtle changes in the tertiary structure, which increased the thermodynamic stability of αA-crystallin. This mutation induced the exposure of additional client protein binding sites on αA-crystallin. Altogether, our data suggest that MGO-modification of the conserved R12 in αA-crystallin to hydroimidazolone may play an important role in reducing protein aggregation in the lens during aging and cataract formation

Withanolides-Induced Breast Cancer Cell Death Is Correlated with Their Ability to Inhibit Heat Protein 90

Withanolides are a large group of steroidal lactones found in Solanaceae plants that exhibit potential anticancer activities. We have previously demonstrated that a withanolide, tubocapsenolide A, induced cycle arrest and apoptosis in human breast cancer cells, which was associated with the inhibition of heat shock protein 90 (Hsp90). To investigate whether other withanolides are also capable of inhibiting Hsp90 and to analyze the structure-activity relationships, nine withanolides with different structural properties were tested in human breast cancer cells MDA-MB-231 and MCF-7 in the present study. Our data show that the 2,3-unsaturated double bond-containing withanolides inhibited Hsp90 function, as evidenced by selective depletion of Hsp90 client proteins and induction of Hsp70. The inhibitory effect of the withanolides on Hsp90 chaperone activity was further confirmed using in vivo heat shock luciferase activity recovery assays. Importantly, Hsp90 inhibition by the withanolides was correlated with their ability to induce cancer cell death. In addition, the withanolides reduced constitutive NF-κB activation by depleting IκB kinase complex (IKK) through inhibition of Hsp90. In estrogen receptor (ER)-positive MCF-7 cells, the withanolides also reduced the expression of ER, and this may be partly due to Hsp90 inhibition. Taken together, our results suggest that Hsp90 inhibition is a general feature of cytotoxic withanolides and plays an important role in their anticancer activity

Low-Resolution Face Recognition

Whilst recent face-recognition (FR) techniques have made significant progress on recognising constrained high-resolution web images, the same cannot be said on natively unconstrained low-resolution images at large scales. In this work, we examine systematically this under-studied FR problem, and introduce a novel Complement Super-Resolution and Identity (CSRI) joint deep learning method with a unified end-to-end network architecture. We further construct a new large-scale dataset TinyFace of native unconstrained low-resolution face images from selected public datasets, because none benchmark of this nature exists in the literature. With extensive experiments we show there is a significant gap between the reported FR performances on popular benchmarks and the results on TinyFace, and the advantages of the proposed CSRI over a variety of state-of-the-art FR and super-resolution deep models on solving this largely ignored FR scenario. The TinyFace dataset is released publicly at: https://qmul-tinyface.github.io/.Comment: Accepted by 14th Asian Conference on Computer Visio