Background: We demonstrated that circulating tumor cell (CTC) number at baseline and follow-up is an independent prognostic factor in metastatic colorectal cancer (mCRC). This analysis was undertaken ...to explore whether patient and treatment characteristics impact the prognostic value of CTCs.
Patients and methods: CTCs were enumerated with immunomagnetic separation from the blood of 430 patients with mCRC at baseline and on therapy. Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of ≥3 or <3 CTCs/7.5ml, respectively. Subgroups were analyzed by line of treatment, liver involvement, receipt of oxaliplatin, irinotecan, or bevacizumab, age, and Eastern Cooperative Oncology Group performance status (ECOG PS).
Results: Seventy-one percent of deaths have occurred. Median follow-up for living patients is 25.8 months. For all patients, progression-free survival (PFS) and overall survival (OS) for unfavorable compared with favorable baseline CTCs is shorter (4.4 versus 7.8 m, P=0.004 for PFS; 9.4 versus 20.6 m, P<0.0001 for OS). In all patient subgroups, unfavorable baseline CTC was associated with inferior OS (P<0.001). In patients receiving first- or second-line therapy (P=0.003), irinotecan (P=0.0001), having liver involvement (P=0.002), ≥65 years (P=0.0007), and ECOG PS of zero (P=0.04), unfavorable baseline CTC was associated with inferior PFS.
Conclusion: Baseline CTC count is an important prognostic factor within specific subgroups defined by treatment or patient characteristics.
We present a new measurement of the positive muon magnetic anomaly, a_{μ}≡(g_{μ}-2)/2, from the Fermilab Muon g-2 Experiment using data collected in 2019 and 2020. We have analyzed more than 4 times ...the number of positrons from muon decay than in our previous result from 2018 data. The systematic error is reduced by more than a factor of 2 due to better running conditions, a more stable beam, and improved knowledge of the magnetic field weighted by the muon distribution, ωover ˜_{p}^{'}, and of the anomalous precession frequency corrected for beam dynamics effects, ω_{a}. From the ratio ω_{a}/ωover ˜_{p}^{'}, together with precisely determined external parameters, we determine a_{μ}=116 592 057(25)×10^{-11} (0.21 ppm). Combining this result with our previous result from the 2018 data, we obtain a_{μ}(FNAL)=116 592 055(24)×10^{-11} (0.20 ppm). The new experimental world average is a_{μ}(exp)=116 592 059(22)×10^{-11} (0.19 ppm), which represents a factor of 2 improvement in precision.
A new highly sensitive method of looking for electric dipole moments of charged particles in storage rings is described. The major systematic errors inherent in the method are addressed and ways to ...minimize them are suggested. It seems possible to measure the muon EDM to levels that test speculative theories beyond the standard model.
As treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. We tested the hypothesis that circulating tumor cells ...(CTCs) could predict clinical outcome in patients with mCRC.
In a prospective multicenter study, CTCs were enumerated in the peripheral blood of 430 patients with mCRC at baseline and after starting first-, second-, or third-line therapy. CTCs were measured using an immunomagnetic separation technique.
Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of three or more or less than three CTCs/7.5 mL, respectively. Patients with unfavorable compared with favorable baseline CTCs had shorter median progression-free survival (PFS; 4.5 v 7.9 months; P = .0002) and overall survival (OS; 9.4 v 18.5 months; P < .0001). Differences persisted at 1 to 2, 3 to 5, 6 to 12, and 13 to 20 weeks after therapy. Conversion of baseline unfavorable CTCs to favorable at 3 to 5 weeks was associated with significantly longer PFS and OS compared with patients with unfavorable CTCs at both time points (PFS, 6.2 v 1.6 months; P = .02; OS, 11.0 v 3.7 months; P = .0002). Among nonprogressing patients, favorable compared with unfavorable CTCs within 1 month of imaging was associated with longer survival (18.8 v 7.1 months; P < .0001). Baseline and follow-up CTC levels remained strong predictors of PFS and OS after adjustment for clinically significant factors.
The number of CTCs before and during treatment is an independent predictor of PFS and OS in patients with metastatic colorectal cancer. CTCs provide prognostic information in addition to that of imaging studies.
Surface waters play a potentially important role in the global carbon balance. Dissolved organic carbon (DOC) fluxes are a major transfer of terrestrial carbon to river systems, and the fate of DOC ...in aquatic systems is poorly constrained. We used a unique combination of spatially distributed sampling of three DOC fractions throughout a river network and modeling to quantify the net removal of terrestrial DOC during a summer base flow period. We found that aquatic reactivity of terrestrial DOC leading to net loss is low, closer to conservative chloride than to reactive nitrogen. Net removal occurred mainly from the hydrophobic organic acid fraction, while hydrophilic and transphilic acids showed no net change, indicating that partitioning of bulk DOC into different fractions is critical for understanding terrestrial DOC removal. These findings suggest that river systems may have only a modest ability to alter the amounts of terrestrial DOC delivered to coastal zones.
Key Points
Low net removal of terrestrial DOC during transport through river networks
HPOA is removed more rapidly than other terrestrial DOC forms
Findings contrast with DOC reactivity measured during other studies
The anomalous magnetic moment of the negative muon has been measured to a precision of 0.7 ppm (ppm) at the Brookhaven Alternating Gradient Synchrotron. This result is based on data collected in ...2001, and is over an order of magnitude more precise than the previous measurement for the negative muon. The result a(mu(-))=11 659 214(8)(3) x 10(-10) (0.7 ppm), where the first uncertainty is statistical and the second is systematic, is consistent with previous measurements of the anomaly for the positive and the negative muon. The average of the measurements of the muon anomaly is a(mu)(exp)=11 659 208(6) x 10(-10) (0.5 ppm).
To determine visual acuity improvement in children with strabismic and combined strabismic-anisometropic (combined-mechanism) amblyopia treated with optical correction alone and to explore factors ...associated with improvement.
Prospective, multicenter, cohort study.
We included 146 children 3 to <7 years old with previously untreated strabismic amblyopia (n = 52) or combined-mechanism amblyopia (n = 94).
Optical treatment was provided as spectacles (prescription based on a cycloplegic refraction) that were worn for the first time at the baseline visit. Visual acuity with spectacles was measured using the Amblyopia Treatment Study HOTV visual acuity protocol at baseline and every 9 weeks thereafter until no further improvement in visual acuity. Ocular alignment was assessed at each visit.
Visual acuity 18 weeks after baseline.
Overall, amblyopic eye visual acuity improved a mean of 2.6 lines (95% confidence interval CI, 2.3-3.0), with 75% of children improving ≥ 2 lines and 54% improving ≥ 3 lines. Resolution of amblyopia occurred in 32% (95% CI, 24%-41%) of the children. The treatment effect was greater for strabismic amblyopia than for combined-mechanism amblyopia (3.2 vs 2.3 lines; adjusted P = 0.003). Visual acuity improved regardless of whether eye alignment improved.
Optical treatment alone of strabismic and combined-mechanism amblyopia results in clinically meaningful improvement in amblyopic eye visual acuity for most 3- to <7-year-old children, resolving in at least one quarter without the need for additional treatment. Consideration should be given to prescribing refractive correction as the sole initial treatment for children with strabismic or combined-mechanism amblyopia before initiating other therapies.
The authors have no proprietary or commercial interest in any of the materials discussed in this article.
The t(4;14) translocation in multiple myeloma (MM) simultaneously dysregulates two apparent oncogenes: fibroblast growth factor receptor 3 (FGFR3) controlled by the 3' immunoglobulin heavy chain ...enhancer on der(14) and MMSET controlled by the intronic Emu enhancer on der(4). Although all MM tumors and cell lines with a t(4;14) translocation have dysregulated MMSET, about 25% do not express FGFR3. Therefore, the function of dysregulated wild-type (WT) FGFR3 in the pathogenesis of MM remains unclear. We developed a murine transgenic (TG) model in which WT FGFR3 is overexpressed in B lymphoid cells. Although high levels of FGFR3 resulted in lymphoid hyperplasia in about one-third of older mice, no increase in tumorigenesis was observed. However, double TG FGFR3/Myc mice develop mature B lymphoma tumors that occur with a higher penetrance and shorter latency than in single TG Myc mice (P=0.006). We conclude that expression of high levels of WT FGFR3 can be oncogenic and cooperate with MYC to generate B lymphoid tumors. This suggests that dysregulated FGFR3 expression is likely to be essential at least for the early stages of pathogenesis of MM tumors that have a t(4;14) translocation.
Analytic expressions for the potentials and fields of flat and cylindrical plates, including the fringe fields, are given. The present analysis extends and simplifies the current expression for the ...fields of flat plates and develops expressions for the fringe fields of cylindrical plates in terms of polar coordinates. The development of a fortran program to output the field strength at a given location within the Proton Electric Dipole Moment (Proton EDM) ring is then described. Fourth-order Runge-Kutta integration is used to investigate the effect of fringe fields on particle and spin dynamics with precision tracking in the proposed Proton EDM experiment.
This paper describes a time-marking system that enables a measurement of the in-plane (horizontal) polarization of a 0.97−GeV/c deuteron beam circulating in the Cooler Synchrotron (COSY) at the ...Forschungszentrum Jülich. The clock time of each polarimeter event is used to unfold the 120-kHz spin precession and assign events to bins according to the direction of the horizontal polarization. After accumulation for one or more seconds, the down-up scattering asymmetry can be calculated for each direction and matched to a sinusoidal function whose magnitude is proportional to the horizontal polarization. This requires prior knowledge of the spin tune or polarization precession rate. An initial estimate is refined by resorting the events as the spin tune is adjusted across a narrow range and searching for the maximum polarization magnitude. The result is biased toward polarization values that are too large, in part because of statistical fluctuations but also because sinusoidal fits to even random data will produce sizable magnitudes when the phase is left free to vary. An analysis procedure is described that matches the time dependence of the horizontal polarization to templates based on emittance-driven polarization loss while correcting for the positive bias. This information will be used to study ways to extend the horizontal polarization lifetime by correcting spin tune spread using ring sextupole fields and thereby to support the feasibility of searching for an intrinsic electric dipole moment using polarized beams in a storage ring. This paper is a combined effort of the Storage Ring EDM collaboration and the JEDI collaboration.
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