Fully nonlinear excitations of non-Abelian plasma

We investigate fully nonlinear, non-Abelian excitations of quark-antiquark plasma, using relativistic fluid theory in cold plasma approximation. There are mainly three important nonlinearities, coming from various sources such as non-Abelian interactions of Yang-Mills (YM) fields, Wong's color dynamics and plasma nonlinearity, in our model. By neglecting nonlinearities due to plasma and color dynamics we get back the earlier results of Blaizot {\it et. al.}, Phys. Rev. Lett. 72, 3317 (1994). Similarly, by neglecting YM fields nonlinearity and plasma nonlinearity, it reduces to the model of Gupta {\it et. al.}, Phys. Lett. B498, 223 (2005). Thus we have the most general non-Abelian mode of quark-gluon plasma (QGP). Further, our model resembles the problem of propagation of laser beam through relativistic plasma, Physica 9D, 96 (1983). in the absence of all non-Abelian interactions.Comment: 8 pages, 2 figures, articl

Statistical mechanics of confined quantum particles

We develop statistical mechanics and thermodynamics of Bose and Fermi systems in relativistic harmonic oscillator (RHO) confining potential, which may be applicable in quark gluon plasma (QGP), astrophysics, Bose-Einstein condensation (BEC), condensed matter physics etc. Detailed study of QGP system is carried out and compared with lattice results. Further, as an application, our equation of state (EoS) of QGP is used to study compact stars like quark star.Comment: 9 pages, 2 figures, articl

Strongly Coupled Quark Gluon Plasma (SCQGP)

We propose that the reason for the non-ideal behavior seen in lattice simulation of quark gluon plasma (QGP) and relativistic heavy ion collisions (URHICs) experiments is that the QGP near T_c and above is strongly coupled plasma (SCP), i.e., strongly coupled quark gluon plasma (SCQGP). It is remarkable that the widely used equation of state (EoS) of SCP in QED (quantum electrodynamics) very nicely fits lattice results on all QGP systems, with proper modifications to include color degrees of freedom and running coupling constant. Results on pressure in pure gauge, 2-flavors and 3-flavors QGP, are all can be explained by treating QGP as SCQGP as demonstated here.Energy density and speed of sound are also presented for all three systems. We further extend the model to systems with finite quark mass and a reasonably good fit to lattice results are obtained for (2+1)-flavors and 4-flavors QGP. Hence it is the first unified model, namely SCQGP, to explain the non-ideal QGP seen in lattice simulations with just two system dependent parameters.Comment: Revised with corrections and new results, Latex file (11 pages), postscript file of 7 figure

Metabolomics and pharmacogenetics based 5-fluorouracil monitoring in colorectal cancer patients

Objective: To provide quick and accurate clinical diagnostic tools those are currently not available leading to improper management of colorectal cancer (CRC) patients. Methods: The metabolomic profiles of 10 CRC patients treated with 5-fluorouracil and 24 healthy volunteers were analysed. The subjects were genotyped for UGT1A1*28, DPYD 1896 T>C and DPYD*5. Results: Our results show alterations in the metabolism of bile acid, glycolysis and fatty acid in patients. The distinctive metabolite profiles established using PLSDA identify several biomarkers for diagnostic use in clinical settings. The predictive PLSDA model revealed 100% accuracy of metabolites differentiating CRC patients and healthy volunteers. In addition, the metabolic profiles associated with different genotypes of DPYD and UGT1A1 explains the impact of genetic variation on differential drug responses. Conclusion: Pharmacogenetics and metabolomics profiles are potential platforms for more comprehensive monitoring of patient's disease progress and drug response. Further study is however needed to validate the use of biomarkers identified

A solution of the coincidence problem based on the recent galactic core black hole mass density increase

A mechanism capable to provide a natural solution to two major cosmological problems, i.e. the cosmic acceleration and the coincidence problem, is proposed. A specific brane-bulk energy exchange mechanism produces a total dark pressure, arising when adding all normal to the brane negative pressures in the interior of galactic core black holes. This astrophysically produced negative dark pressure explains cosmic acceleration and why the dark energy today is of the same order to the matter density for a wide range of the involved parameters. An exciting result of the analysis is that the recent rise of the galactic core black hole mass density causes the recent passage from cosmic deceleration to acceleration. Finally, it is worth mentioning that this work corrects a wide spread fallacy among brane cosmologists, i.e. that escaping gravitons result to positive dark pressure.Comment: 14 pages, 3 figure

Autologous stem cell transplantation with low-dose cyclophosphamide to improve mucosal healing in adults with refractory Crohn's disease: the ASTIClite RCT

Some text in this abstract has been reproduced from Lindsay J, Din S, Hawkey C, Hind D, Irving P, Lobo A, et al. OFR-9 An RCT of autologous stem-cell transplantation in treatment refractory Crohn’s disease (low-intensity therapy evaluation): ASTIClite. Gut 2021;70(Suppl. 4):A4. Background Treatment-refractory Crohn’s disease is characterised by chronic symptoms, poor quality of life and high costs to the NHS, and through days of work lost by patients. A previous trial of autologous haematopoietic stem cell transplant (HSCT) failed its end point of medication-free clinical remission for 3 months with no evidence of disease activity, and reported high toxicity. Subsequent studies suggest that HSCT achieves complete mucosal healing in 50% of patients, and that toxicity likely relates to the cyclophosphamide dose. Objectives The primary objective was to assess the efficacy of HSCTlite (HSCT with low-dose cyclophosphamide) compared with standard care for inducing regression of intestinal ulceration in patients with refractory Crohn’s disease at week 48. Secondary objectives included the assessment of disease activity, quality of life and regimen safety. Mechanistic objectives included immune reconstitution after HSCTlite. Design Two-arm, parallel-group randomised controlled trial with a 2 : 1 (intervention : control) allocation ratio. Setting Nine NHS trusts (eight trusts were recruitment sites; one trust was a treatment-only site). Participants Adults with treatment-refractory Crohn’s disease, for whom surgery was inappropriate or who had declined surgery. Interventions The intervention treatment was HSCTlite using cyclophosphamide, and the control was any current available treatment for Crohn’s disease, apart from stem cell transplantation. Main outcomes The primary outcome was treatment success at week 48 [mucosal healing (Simple Endoscopic Score for Crohn’s Disease ulcer subscore of 0) without surgery or death], assessed by central readers blinded to allocation and timing of assessment. Key secondary outcomes were clinical remission, Simple Endoscopic Score for Crohn’s Disease scores at week 48, change in Crohn’s Disease Activity Index scores and safety. Results The trial was halted owing to Suspected unexpected serious adverse events that took place after randomising 23 patients (HSCTlite arm, n = 13; usual-care arm, n = 10). Ten out of the 13 patients randomised to the HSCTlite arm received the intervention and nine (one death) reached the 48-week follow-up. In the usual-care arm 9 out of the 10 patients randomised reached the 48-week follow-up (one ineligible). The primary outcome was available for 7 out of 10 HSCTlite patients (including the patient who died) and six out of nine usual-care patients. Absence of endoscopic ulceration without surgery or death was reported in three out of seven (43%) HSCTlite patients, compared with zero out of six (0%) usual-care patients. Centrally read Simple Endoscopic Score for Crohn’s Disease scores [mean (standard deviation)] were 10.8 (6.3) and 10.0 (6.1) at baseline, compared with 2.8 (2.9) and 18.7 (9.1) at week 48, in the HSCT and usual-care arms, respectively. Clinical remission (Crohn’s Disease Activity Index scores of < 150) occurred in 57% and 17% of patients in the HSCTlite and usual-care arms, respectively, at week 48. Serious adverse events were more frequent in the HSCTlite arm [38 in 13 (100%) patients] than in the usual-care arm [16 in 4 (40%) patients]. Nine suspected unexpected serious adverse reactions were reported in six HSCTlite patients, including three cases of delayed renal failure due to proven thrombotic microangiopathy. Two HSCTlite patients died. Conclusions Within the limitations of reduced patient recruitment and numbers of patients assessed, HSCTlite meaningfully reduced endoscopic disease activity, with three patients experiencing resolution of ulceration. Suspected unexpected serious adverse reactions, particularly relating to thrombotic microangiopathy, make this regimen unsuitable for future clinical use. Limitations The early trial closure prevented complete recruitment, and the impact of the coronavirus pandemic prevented completion of some study investigations. Small participant numbers meant analysis could only be descriptive. Future work Owing to undetermined aetiology of thrombotic microangiopathy, further trials of HSCTlite in this population are not considered appropriate. Priorities should be to determine optimal treatment strategies for patients with refractory Crohn’s disease, including those with a stoma or multiple previous resections

Safety and efficacy of autologous haematopoietic stem-cell transplantation with low-dose cyclophosphamide mobilisation and reduced intensity conditioning versus standard of care in refractory Crohn’s disease (ASTIClite): an open-label, multicentre, randomised controlled trial

Background A previous controlled trial of autologous haematopoietic stem-cell transplantation (HSCT) in patients with refractory Crohn's disease did not meet its primary endpoint and reported high toxicity. We aimed to assess the safety and efficacy of HSCT with an immune-ablative regimen of reduced intensity versus standard of care in this patient population. Methods This open-label, multicentre, randomised controlled trial was conducted in nine National Health Service hospital trusts across the UK. Adults (aged 18–60 years) with active Crohn's disease on endoscopy (Simplified Endoscopic Score for Crohn's Disease [SES-CD] ulcer sub-score of ≥2) refractory to two or more classes of biological therapy, with no perianal or intra-abdominal sepsis or clinically significant comorbidity, were recruited. Participants were centrally randomly assigned (2:1) to either HSCT with a reduced dose of cyclophosphamide (intervention group) or standard care (control group). Randomisation was stratified by trial site by use of random permuted blocks of size 3 and 6. Patients in the intervention group underwent stem-cell mobilisation (cyclophosphamide 1 g/m2 with granulocyte colony-stimulating factor (G-CSF) 5 μg/kg) and stem-cell harvest (minimum 2·0 × 106 CD34+ cells per kg), before conditioning (fludarabine 125 mg/m2, cyclophosphamide 120 mg/kg, and rabbit anti-thymocyte globulin [thymoglobulin] 7·5 mg/kg in total) and subsequent stem-cell reinfusion supported by G-CSF. Patients in the control group continued any available conventional, biological, or nutritional therapy. The primary outcome was absence of endoscopic ulceration (SES-CD ulcer sub-score of 0) without surgery or death at week 48, analysed in the intention-to-treat population by central reading. This trial is registered with the ISRCTN registry, 17160440. Findings Between Oct 18, 2018, and Nov 8, 2019, 49 patients were screened for eligibility, of whom 23 (47%) were randomly assigned: 13 (57%) to the intervention group and ten (43%) to the control group. In the intervention group, ten (77%) participants underwent HSCT and nine (69%) reached 48-week follow-up; in the control group, nine (90%) reached 48-week follow-up. The trial was halted in response to nine reported suspected unexpected serious adverse reactions in six (46%) patients in the intervention group, including renal failure due to proven thrombotic microangiopathy in three participants and one death due to pulmonary veno-occlusive disease. At week 48, absence of endoscopic ulceration without surgery or death was reported in three (43%) of seven participants in the intervention group and in none of six participants in the control group with available data. Serious adverse events were more frequent in the intervention group (38 in 13 [100%] patients) than in the control group (16 in four [40%] patients). A second patient in the intervention group died after week 48 of respiratory and renal failure. Interpretation Although HSCT with an immune-ablative regimen of reduced intensity decreased endoscopic disease activity, significant adverse events deem this regimen unsuitable for future clinical use in patients with refractory Crohn's disease. Funding Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership