Design and Performance Evaluation of DL MAC Scheduling Model in LTE

In case of Long Term Evolution (LTE), the scheduler in the MAC layer of the eNodeB allocates the available radio resources among different UEs in a cell through proper handling of priority. The scheduling method used largely impacts the throughput of individual users as well as throughput of the cell. It is worthwhile to check on the throughput conditions for different scheduling scenarios before the actual deployment of LTE. This would help design the algorithm of the scheduler at the eNodeB appropriately. In this dissertation, the throughput conditions require to investigate for different scheduling methods in LTE

Comparative study between percutaneous pinning and ligamentotaxis using external fixator in the management of distal end radius fracture in adults: a prospective study

Background: Fractures of distal end of radius are beginning at the proximal end of pronator quadratus and ending at the radio-carpal articulation. The final aim in the management of comminuted intra-articular fractures of distal radius is to restore normal function. Recognition of patterns that are inherently unstable and therefore necessitate additional forms of fixation to secure and maintain reduction and prevent late collapse is the key for successful management of the more complex fractures of distal radius. The aim is to study the functional outcome of surgical management of comminuted intra-articular fractures of distal end radius by comparing 2 different methods of surgical interventions.Methods: In study of 30 cases treated in period from March 2008 to September 2009 at St. Martha’s Hospital by ligamentotaxis and percutaneous pinning, all patients with compound fractures, Frykman's IV, V, VI, VII and VIII, comminuted fractures and in fractures where reduction was lost following closed reduction and POP application were taken into consideration.Results: The average age in males were 41.35 years and female were 35 years. 12 (40%) fractures were type VII, 6 (20%) were type VIII, 9 (30%) were type IV and 3 cases (10%) was type V. functional results in ligamentotaxis group (G1) 7 cases had excellent results (47%), in percutaneous pinning (G2), 3 cases had excellent result (20%). In ligamentotaxis group (G1) 3 had good results (20%), in percutaneous group (G2) 6 had good results (40%). In ligamentotaxis group (G1) 5 had poor results (33%), in percutaneous pinning group (G2) 6 had poor results (40%).Conclusions: In comparative studies, external fixation with percutaneous pinning consistently achieves better anatomical results as compared to percutaneous pinning alone. In our study, also this technique has shown satisfactory result that lead to high rate of return to pre-injury status, high level of patient satisfaction and low rate of complications

Toll-like receptor expression in crypt epithelial cells, putative stem cells and intestinal myofibroblasts isolated from controls and patients with inflammatory bowel disease

The aim of our studies was to investigate the expression of Toll-like receptor (TLR)-2 and TLR-4 (and in some studies TLR-5) in myofibroblasts and small and large intestinal crypt epithelial cells from control patients and those affected by Crohn's disease and ulcerative colitis. Isolated and disaggregated crypt epithelial cells and monolayers of myofibroblasts were used for studies by reverse transcription–polymerase chain reaction (RT–PCR), real-time RT–PCR, flow cytometry, immunocytochemistry and Western blot analysis. Compared to control cells, crypt epithelial cells isolated from active ulcerative colitis and Crohn's disease colonic mucosal samples showed significantly higher expression of TLR-2 and TLR-4 transcripts and protein (on the cell surface). There was also enhanced expression of TLR-4 in crypt cells from ileal Crohn's disease. Expression of TLR-2 and TLR-4 transcripts in crypt epithelial cells isolated from inflamed mucosa of distal ulcerative colitis did not differ significantly from such cells obtained from the normal proximal colon. Crypt epithelial cells with side population characteristics (putative stem cells) also expressed transcripts and protein for TLR-2, TLR-4 and TLR-5. Colonic myofibroblast expression of these TLRs was much weaker than in crypt epithelial cells. In conclusion, enhanced TLR-2 and TLR-4 expression by crypt epithelial cells in active inflammatory bowel disease likely reflects greater ability to respond to microbial products. Results from our studies using mucosal samples from patients with distal ulcerative colitis suggest that the enhanced expression of these TLRs could be constitutive. TLR-2, TLR-4 and TLR-5 expression by stem cells imply ability to respond to distinct bacterial products

11β hydroxysteroid dehydrogenase type 1 transgenic mesenchymal stem cells attenuate inflammation in models of sepsis

Background: Human bone marrow mesenchymal stem cell (MSC) administration reduces inflammation in pre-clinical models of sepsis and sepsis-related lung injury, however clinical efficacy in patients has not yet been demonstrated. We previously showed that Alveolar Macrophage (AM) 11β-hydroxysteroid dehydrogenase type-1 (HSD-1) autocrine signalling is impaired in critically ill sepsis patients, which promotes inflammatory injury. Administration of transgenic MSCs (tMSCs) which overexpress HSD-1 may enhance the anti-inflammatory effects of local glucocorticoids and be more effective at reducing inflammation in sepsis than cellular therapy alone.Methods: MSCs were transfected using a recombinant lentiviral vector containing the HSD-1 and GPF transgenes under the control of a tetracycline promoter. Thin layer chromatography assessed HSD-1 reductase activity in tMSCs. Mesenchymal stem cell phenotype was assessed by flow cytometry and bi-lineage differentiation. HSD-1 tMSCs were co-cultured with LPS-stimulated monocyte-derived macrophages (MDMs) from healthy volunteers prior to assessment of pro-inflammatory cytokine release. HSD-1 tMSCs were administered intravenously to mice undergoing caecal ligation and puncture (CLP).Results: MSCs were transfected with an efficiency of 91.1%, and maintained an MSC phenotype. Functional HSD-1 activity was demonstrated in tMSCs, with predominant reductase cortisol activation (peak 8.23 pM/hour/100,000 cells). HSD-1 tMSC co-culture with LPS-stimulated MDMs suppressed TNFα and IL-6 release. Administration of transgene activated HSD-1 tMSCs in a murine model of CLP attenuated neutrophilic inflammation more effectively than transgene inactive tMSCs (medians 0.403 v 1.36 × 106/ml, p = 0.033).Conclusion: The synergistic impact of HSD-1 transgene expression and MSC therapy attenuated neutrophilic inflammation in a mouse model of peritoneal sepsis more effectively than MSC therapy alone. Future studies investigating the anti-inflammatory capacity of HSD-1 tMSCs in models of sepsis-related direct lung injury and inflammatory diseases are required

Dexamethasone impairs the expression of antimicrobial mediators in lipopolysaccharide-activated primary macrophages by inhibiting both expression and function of interferon β

Glucocorticoids potently inhibit expression of many inflammatory mediators, and have been widely used to treat both acute and chronic inflammatory diseases for more than seventy years. However, they can have several unwanted effects, amongst which immunosuppression is one of the most common. Here we used microarrays and proteomic approaches to characterise the effect of dexamethasone (a synthetic glucocorticoid) on the responses of primary mouse macrophages to a potent pro-inflammatory agonist, lipopolysaccharide (LPS). Gene ontology analysis revealed that dexamethasone strongly impaired the lipopolysaccharide-induced antimicrobial response, which is thought to be driven by an autocrine feedback loop involving the type I interferon IFNβ. Indeed, dexamethasone strongly and dose-dependently inhibited the expression of IFNβ by LPS-activated macrophages. Unbiased proteomic data also revealed an inhibitory effect of dexamethasone on the IFNβ-dependent program of gene expression, with strong down-regulation of several interferon-induced antimicrobial factors. Surprisingly, dexamethasone also inhibited the expression of several antimicrobial genes in response to direct stimulation of macrophages with IFNβ. We tested a number of hypotheses based on previous publications, but found that no single mechanism could account for more than a small fraction of the broad suppressive impact of dexamethasone on macrophage type I interferon signaling, underlining the complexity of this pathway. Preliminary experiments indicated that dexamethasone exerted similar inhibitory effects on primary human monocyte-derived or alveolar macrophages.</p

Fully Automated Electrophysiological Model Personalisation Framework from CT Imaging

International audienceThere has been a recent growing interest for cardiac computed tomography (CT) imaging in the electrophysiological community. This imaging modality indeed allows to locate and assess post-infarct scar heterogeneity, allowing to predict zones of abnormal electrical activity and even personalise EP models. To this end, most of the literature uses manually segmented CT images where one fundamental information is extracted, the myocardial wall thickness. In this paper, we evaluate the impact of using an automated deep learning (DL) methodology to segment the left ventricular wall and extract relevant scar information on the resulting personalised models. Using CT images from 8 patients that were not used during the DL training, we show that the automated segmentation is very similar to the manual one (median Dice score: 0.9). Thickness information obtained this way is also very close to the manual one (median difference: 0.7 mm). A wavefront propagation model personalisation framework based on this thickness information does not show relevant differences in its output (median difference in local activation time: 2 ms), proving its robustness. Bipolar electrograms, simulated through a novel approach, do not differ significantly between manual and automated segmentations (Pearson's r: 0.99)

Cryoballoon pulmonary vein isolation as first-line treatment of typical atrial flutter: long-term outcomes of the CRAFT trial

\ua9 The Author(s) 2024.Background: CRAFT was an international, multicentre, randomised controlled trial across 11 sites in the United UK and Switzerland. Given the evidence that pulmonary vein triggers may be responsible for atrial flutter (AFL) as well as atrial fibrillation (AF), we hypothesised that cryoballoon pulmonary vein isolation (PVI) would provide greater symptomatic arrhythmia reduction than cavotricuspid isthmus (CTI) ablation, whilst also reducing the subsequent burden of AF. Twelve-month outcomes were previously reported. In this study, we report the extended outcomes of the CRAFT study to 36 months. Methods: Patients with typical AFL and no evidence of AF were randomised 1:1 to cryoballoon PVI or radiofrequency CTI. All patients received an implantable loop recorder (ILR) for continuous cardiac rhythm monitoring. The primary outcome was time-to-symptomatic arrhythmia recurrence &gt; 30 s. Secondary outcomes included time-to-first-AF episode ≥ 2 min. The composite safety outcome included death, stroke and procedural complications. Results: A total of 113 patients were randomised to cryoballoon PVI (n = 54) or radiofrequency CTI ablation (n = 59). Ninety-one patients reconsented for extended follow-up beyond 12 months. There was no difference in the primary outcome between arms, with the primary outcome occurring in 12 PVI vs 11 CTI patients (HR 0.97; 95% CI 0.43–2.20; p = 0.994). AF ≥ 2 min was significantly less frequent in the PVI arm, affecting 26 PVI vs 36 CTI patients (HR 0.48; 95% CI 0.29–0.79; p = 0.004). The composite safety outcome occurred in 5 PVI and 6 CTI patients (p = 0.755). Conclusion: Cryoballoon PVI shows similar efficacy to radiofrequency CTI ablation in reducing symptomatic arrhythmia recurrence in patients presenting with isolated typical AFL but significantly reduces the occurrence of subsequent AF. Graphical Abstract: (Figure presented.)

Inflammation Dynamically Regulates Steroid Hormone Metabolism and Action within Macrophages in Rheumatoid Arthritis

Rationale: In inflammatory diseases such as rheumatoid arthritis (RA), steroid metabolism is a central component mediating the actions of immuno-modulatory glucocorticoids and sex steroids. However, the regulation and function of cellular steroid metabolism within key leukocyte populations such as macrophages remain poorly defined. In this study, the inflammatory regulation of global steroid metabolism was assessed in RA macrophages. Methods: Bulk RNA-seq data from RA synovial macrophages was used to assess transcripts encoding key enzymes in steroid metabolism and signalling. Changes in metabolism were assessed in synovial fluids, correlated to measures of disease activity and functionally validated in primary macrophage cultures. Results: RNA-seq revealed a unique pattern of differentially expressed genes, including changes in genes encoding the enzymes 11β-HSD1, SRD5A1, AKR1C2 and AKR1C3. These correlated with disease activity, favouring increased glucocorticoid and androgen levels. Synovial fluid 11β-HSD1 activity correlated with local inflammatory mediators (TNFα, IL-6, IL-17,), whilst 11β-HSD1, SRD5A1 and AKR1C3 activity correlated with systemic measures of disease and patient pain (ESR, DAS28 ESR, global disease activity). Changes in enzyme activity were evident in inflammatory activated macrophages in vitro and revealed a novel androgen activating role for 11β-HSD1. Together, increased glucocorticoids and androgens were able to suppress inflammation in macrophages and fibroblast-like-synoviocytes. Conclusions: This study underscores the significant increase in androgen and glucocorticoid activation within inflammatory polarized macrophages of the synovium, contributing to local suppression of inflammation. The diminished profile of inactive steroid precursors in postmenopausal women may contribute to disturbances in this process, leading to increased disease incidence and severity.<br/

Best practice standards for the delivery of NHS infection services in the United Kingdom

Infection expertise in the NHS has historically been provided predominantly by hospital-based medical microbiologists responsible for provision of diagnostic services and advice to front-line clinicians. While most hospitals had consultant-led microbiology departments, infectious iiseases departments were based in a small number of specialist centres. The demand for infection expertise is growing in the NHS, driven by advances in medical care, increasing awareness of the impact of antibiotic resistant and healthcare associated infections and threats from emerging infectious diseases. At the same time diagnostic services are being reorganised into pathology networks. The Combined Infection Training (CIT) is delivering a consultant workforce with expertise both in laboratory diagnostic practice and delivery of direct patient care. These changes create challenges for delivery of high quality infection expertise equitably across the NHS. They also offer an opportunity to shape infection services to meet clinical and laboratory demands. To date there has not been an attempt to bring together a single set of best practice guidelines for the requirements of an infection service. This document sets out seven standards. These are written to be practical and flexible according to the diverse ways in which infection expertise may be required across the NHS. It has been prepared by the Clinical Services Committee of the British Infection Association drawing on published evidence and guidance where they exist and on the group's extensive experience of delivering infection services in hospitals across the NHS. It was then refined with input from the RCP Joint Specialist committee (JSC) and the RCPath Specialist Advisory Committee (SAC) and through consultation with the RCPath membership. It has been endorsed by the Royal College of Pathologists and the Royal College of Physicians. It will be reviewed annually by the CSC and updated as additional evidence becomes available

Vitamin D to prevent lung injury following esophagectomy: A randomized, placebo-controlled trial

Objectives: Observational studies suggest an association between vitamin D deficiency and adverse outcomes of critical illness and identify it as a potential risk factor for the development of lung injury. To determine whether pre-operative administration of oral high-dose cholecalciferol ameliorates early acute lung injury post-operatively in adults undergoing elective esophagectomy. Design: A double-blind, randomized, placebo-controlled trial. Setting: Three large UK university hospitals. Patients: Seventy-nine adult patients undergoing elective esophagectomy were randomized. Intervention: A single oral preoperative (3-14 days) dose of 7.5mg (300,000IU; 15mls) cholecalciferol or matched placebo. Measurements and Main Results: Primary outcome was change in extravascular lung water index (EVLWI) at the end of esophagectomy. Secondary outcomes included PaO2:FiO2 ratio, development of lung injury, ventilator and organ-failure free days, 28 and 90 day survival, safety of cholecalciferol supplementation, plasma vitamin D status (25(OH)D, 1,25(OH)2D and vitamin D binding protein), pulmonary vascular permeability index (PVPI) and EVLWI day 1 postoperatively. An exploratory study measured biomarkers of alveolar-capillary inflammation and injury. Forty patients were randomized to cholecalciferol and 39 to placebo. There was no significant change in EVLWI at the end of the operation between treatment groups (placebo median 1.0[IQR 0.4 – 1.8] vs cholecalciferol median 0.4[IQR 0.4 – 1.2] ml/kg, p=0.059). Median PVPI values were significantly lower in the cholecalciferol treatment group (placebo 0.4[IQR 0 – 0.7] vs cholecalciferol 0.1[IQR -0.15 -0.35], p=0.027). Cholecalciferol treatment effectively increased 25(OH)D concentrations but surgery resulted in a decrease in 25(OH)D concentrations at day 3 in both arms. There was no difference in clinical outcomes. Conclusions: High-dose preoperative treatment with oral cholecalciferol was effective at increasing 25(OH)D concentrations, and reduced changes in postoperative PVPI but not EVLWI