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- Guidoboni, G., et al.
(författare)
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How to Reach a Thousand-Second in-Plane Polarization Lifetime with 0.97-GeV/c Deuterons in a Storage Ring
- 2016
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 117:5
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Tidskriftsartikel (refereegranskat)abstract
- We observe a deuteron beam polarization lifetime near 1000 s in the horizontal plane of a magnetic storage ring (COSY). This long spin coherence time is maintained through a combination of beam bunching, electron cooling, sextupole field corrections, and the suppression of collective effects through beam current limits. This record lifetime is required for a storage ring search for an intrinsic electric dipole moment on the deuteron at a statistical sensitivity level approaching 10(-29) e cm.
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- Zumla, A, et al.
(författare)
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Towards host-directed therapies for tuberculosis
- 2015
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Ingår i: Nature reviews. Drug discovery. - : Springer Science and Business Media LLC. - 1474-1784 .- 1474-1776. ; 14:8, s. 511-
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Eversmann, D., et al.
(författare)
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New Method for a Continuous Determination of the Spin Tune in Storage Rings and Implications for Precision Experiments
- 2015
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 115:9
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Tidskriftsartikel (refereegranskat)abstract
- A new method to determine the spin tune is described and tested. In an ideal planar magnetic ring, the spin tune-defined as the number of spin precessions per turn-is given by nu(s) = gamma G (gamma is the Lorentz factor, G the gyromagnetic anomaly). At 970 MeV/c, the deuteron spins coherently process at a frequency of approximate to 120 kHz in the Cooler Synchrotron COSY. The spin tune is deduced from the up-down asymmetry of deuteron-carbon scattering. In a time interval of 2.6 s, the spin tune was determined with a precision of the order 10(-8), and to 1 x 10(-10) for a continuous 100 s accelerator cycle. This renders the presented method a new precision tool for accelerator physics; controlling the spin motion of particles to high precision is mandatory, in particular, for the measurement of electric dipole moments of charged particles in a storage ring.
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- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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- Dierig, A., et al.
(författare)
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A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis
- 2023
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Ingår i: Trials. - : BMC. - 1745-6215. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Linezolid is an effective, but toxic anti-tuberculosis drug that is currently recommended for the treatment of drug-resistant tuberculosis. Improved oxazolidinones should have a better safety profile, while preserving efficacy. Delpazolid is a novel oxazolidinone developed by LegoChem Biosciences Inc. that has been evaluated up to phase 2a clinical trials. Since oxazolidinone toxicity can occur late in treatment, LegoChem Biosciences Inc. and the PanACEA Consortium designed DECODE to be an innovative dose-ranging study with long-term follow-up for determining the exposure-response and exposure-toxicity relationship of delpazolid to support dose selection for later studies. Delpazolid is administered in combination with bedaquiline, delamanid and moxifloxacin.Methods: Seventy-five participants with drug-sensitive, pulmonary tuberculosis will receive bedaquiline, delamanid and moxifloxacin, and will be randomized to delpazolid dosages of 0 mg, 400 mg, 800 mg, 1200 mg once daily, or 800 mg twice daily, for 16 weeks. The primary efficacy endpoint will be the rate of decline of bacterial load on treatment, measured by MGIT liquid culture time to detection from weekly sputum cultures. The primary safety endpoint will be the proportion of oxazolidinone class toxicities; neuropathy, myelosuppression, or tyramine pressor response. Participants who convert to negative liquid media culture by week 8 will stop treatment after the end of their 16-week course and will be observed for relapse until week 52. Participants who do not convert to negative culture will receive continuation phase treatment with rifampicin and isoniazid to complete a six-month treatment course.Discussion: DECODE is an innovative dose-finding trial, designed to support exposure-response modelling for safe and effective dose selection. The trial design allows assessment of occurrence of late toxicities as observed with linezolid, which is necessary in clinical evaluation of novel oxazolidinones. The primary efficacy endpoint is the change in bacterial load, an endpoint conventionally used in shorter dose-finding trials. Long-term follow-up after shortened treatment is possible through a safety rule excluding slow-and non-responders from potentially poorly performing dosages.
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| 19. |
- Heyckendorf, J, et al.
(författare)
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Prediction of anti-tuberculosis treatment duration based on a 22-gene transcriptomic model
- 2021
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 58:3
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Tidskriftsartikel (refereegranskat)abstract
- The World Health Organization recommends standardised treatment durations for patients with tuberculosis (TB). We identified and validated a host-RNA signature as a biomarker for individualised therapy durations for patients with drug-susceptible (DS)- and multidrug-resistant (MDR)-TB.MethodsAdult patients with pulmonary TB were prospectively enrolled into five independent cohorts in Germany and Romania. Clinical and microbiological data and whole blood for RNA transcriptomic analysis were collected at pre-defined time points throughout therapy. Treatment outcomes were ascertained by TBnet criteria (6-month culture status/1-year follow-up). A whole-blood RNA therapy-end model was developed in a multistep process involving a machine-learning algorithm to identify hypothetical individual end-of-treatment time points.Results50 patients with DS-TB and 30 patients with MDR-TB were recruited in the German identification cohorts (DS-GIC and MDR-GIC, respectively); 28 patients with DS-TB and 32 patients with MDR-TB in the German validation cohorts (DS-GVC and MDR-GVC, respectively); and 52 patients with MDR-TB in the Romanian validation cohort (MDR-RVC). A 22-gene RNA model (TB22) that defined cure-associated end-of-therapy time points was derived from the DS- and MDR-GIC data. The TB22 model was superior to other published signatures to accurately predict clinical outcomes for patients in the DS-GVC (area under the curve 0.94, 95% CI 0.9–0.98) and suggests that cure may be achieved with shorter treatment durations for TB patients in the MDR-GIC (mean reduction 218.0 days, 34.2%; p<0.001), the MDR-GVC (mean reduction 211.0 days, 32.9%; p<0.001) and the MDR-RVC (mean reduction of 161.0 days, 23.4%; p=0.001).ConclusionBiomarker-guided management may substantially shorten the duration of therapy for many patients with MDR-TB.
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