While MGMT promoter methylation (mMGMT) is predictive of response to alkylating chemotherapy and guides treatment decisions in glioblastoma, its role in grade 2 and 3 glioma remains unclear. Recent ...data suggest that mMGMT is prognostic of progression-free survival in 1p/19q-codeleted oligodendrogliomas, but an effect on overall survival (OS) has not been demonstrated.
We identified patients with newly diagnosed 1p/19q-codeleted gliomas and known MGMT promoter status in the National Cancer Database from 2010 to 2019. Multivariable Cox proportional hazards regression modeling was used to assess the effect of mMGMT on OS after adjusting for age, sex, race, comorbidity, grade, extent of resection, chemotherapy, and radiotherapy.
We identified 1,297 eligible patients, 938 (72.3%) of whom received chemotherapy in their initial course of treatment. The MGMT promoter was methylated in 1,009 (77.8%) patients. Unmethylated MGMT (uMGMT) was associated with worse survival compared with mMGMT 70% {95% confidence interval (CI), 64%-77%} vs. 81% (95% CI, 78%-85%); P < 0.001; adjusted HR (aHR), 2.35 (95% CI, 1.77-3.14). uMGMT was associated with worse survival in patients who received chemotherapy 63% (95% CI, 55-73%) vs. 80% (95% CI, 76%-84%); P < 0.001; aHR, 2.61 (95% CI, 1.89-3.60) but not in patients who did not receive chemotherapy P = 0.38; HR, 1.31 (95% CI, 0.71-2.42). Similar results were observed regardless of World Health Organization grade and after single- or multiagent chemotherapy.
Our study demonstrates an association between mMGMT and OS in 1p/19q-codeleted gliomas. MGMT promoter status should be considered as a stratification factor in future clinical trials of 1p/19q-codeleted gliomas that use OS as an endpoint.
Bone infection has received increasing attention in recent years as one of the main outstanding clinical problems in orthopaedic-trauma surgery that has not been successfully addressed. In fact, ...infection may develop across a spectrum of patient types regardless of the level of perioperative management, including antibiotic prophylaxis. Some of the main unknown factors that may be involved, and the main targets for future intervention, include more accurate and less invasive diagnostic options, more thorough and accurate debridement protocols, and more potent and targeted antimicrobials. The underlying biology dominates the clinical management of bone infections, with features such as biofilm formation, osteolysis and vascularisation being particularly influential. Based on the persistence of this problem, an improved understanding of the basic biology is deemed necessary to enable innovation in the field. Furthermore, from the clinical side, better evidence, documentation and outreach will be required to translate these innovations to the patient. This review presents the findings and progress of the AO Trauma Clinical Priority Program on the topic of bone infection.
The simultaneous control of the density and particle number of non-neutral plasmas confined in Penning-Malmberg traps is demonstrated. Control is achieved by setting the plasma's density by applying ...a rotating electric field while simultaneously fixing its axial potential via evaporative cooling. This novel method is particularly useful for stabilizing positron plasmas, as the procedures used to collect positrons from radioactive sources typically yield plasmas with variable densities and particle numbers; it also simplifies optimization studies that require plasma parameter scans. The reproducibility achieved by applying this technique to the positron and electron plasmas used by the ALPHA antihydrogen experiment at CERN, combined with other developments, contributed to a 10-fold increase in the antiatom trapping rate.
Hypermutation In Pancreatic Cancer Humphris, Jeremy L; Patch, Ann-Marie; Nones, Katia ...
Gastroenterology (New York, N.Y. 1943),
01/2017, Letnik:
152, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in ...several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.
Context.
The sub-Jovian, or Neptunian, desert is a previously identified region of parameter space where there is a relative dearth of intermediate-mass planets with short orbital periods.
Aims.
We ...present the discovery of a new transiting planetary system within the Neptunian desert, NGTS-14.
Methods.
Transits of NGTS-14Ab were discovered in photometry from the Next Generation Transit Survey (NGTS). Follow-up transit photometry was conducted from several ground-based facilities, as well as extracted from TESS full-frame images. We combine radial velocities from the HARPS spectrograph with the photometry in a global analysis to determine the system parameters.
Results.
NGTS-14Ab has a radius that is about 30 per cent larger than that of Neptune (0.444 ± 0.030
R
Jup
) and is around 70 per cent more massive than Neptune (0.092 ± 0.012
M
Jup
). It transits the main-sequence K1 star, NGTS-14A, with a period of 3.54 days, just far away enough to have maintained at least some of its primordial atmosphere. We have also identified a possible long-period stellar mass companion to the system, NGTS-14B, and we investigate the binarity of exoplanet host stars inside and outside the Neptunian desert using
Gaia
.
Antihydrogen, a positron bound to an antiproton, is the simplest anti-atom. Its structure and properties are expected to mirror those of the hydrogen atom. Prospects for precision comparisons of the ...two, as tests of fundamental symmetries, are driving a vibrant programme of research. In this regard, a limiting factor in most experiments is the availability of large numbers of cold ground state antihydrogen atoms. Here, we describe how an improved synthesis process results in a maximum rate of 10.5 ± 0.6 atoms trapped and detected per cycle, corresponding to more than an order of magnitude improvement over previous work. Additionally, we demonstrate how detailed control of electron, positron and antiproton plasmas enables repeated formation and trapping of antihydrogen atoms, with the simultaneous retention of atoms produced in previous cycles. We report a record of 54 detected annihilation events from a single release of the trapped anti-atoms accumulated from five consecutive cycles.Antihydrogen studies are important in testing the fundamental principles of physics but producing antihydrogen in large amounts is challenging. Here the authors demonstrate an efficient and high-precision method for trapping and stacking antihydrogen by using controlled plasma.
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