We report on experimental studies of polarimetric sensitivity to torsion in spun highly birefringent fibers. Two classes of spun fibers were examined, namely spun side-hole fibers and birefringent ...microstructured fibers with different birefringence dispersion, spin pitches, and spin directions. The polarimetric sensitivity to torsion was determined by monitoring a displacement of the spectral interference fringes arising in the output signal because of interference of polarization modes and induced by an additional fiber twist. Both the experimental results and the analytical predictions showed that the sensitivity to torsion normalized to the fringe width in the spun highly birefringent fibers increased asymptotically with the twist rate to the value of 1/ π rad
. We have also studied the polarimetric response to temperature in the spun side-hole fibers. We have found that, in contrast to the torsional sensitivity, the temperature sensitivity decays asymptotically to zero with increasing fiber twist rate. Therefore, the spun fibers with short spin pitches are especially well suited for torsion measurements because the torsional sensitivity and the range of linear response are both enhanced in such fibers, while at the same time, the cross-sensitivity to temperature is reduced.
Helical core fibers (HCFs) suffer from low coupling efficiency and unavoidable excitation of higher order modes below the cutoff wavelength because of a core tilt with respect to the symmetry axis of ...the cladding. We propose an effective way of increasing the coupling efficiency to a HCF by untwisting its beginning section in a hydrogen flame. The proposed solution provides also a control over the excitation of higher order modes in HCFs and can be applied in splicing as well as in a free-space launching configuration. We experimentally demonstrate that by using the proposed method, the coupling efficiency between a SMF-28 and HCF can be increased to the level reachable for straight fibers, which is limited only by a modal fields mismatch. We also present detailed numerical and analytical studies of the coupling efficiency between a HCF and SMF versus the pitch distance in the partially untwisted input section of the HCF, which takes into account fundamental and higher-order modes.
Monosomal karyotype (MK) and complex karyotype (CK) are poor prognostic factors in acute myeloid leukemia (AML). A comprehensive analysis of cytogenetic and clinical factors influencing an outcome of ...AML-CK
+
was performed. The impact of cladribine containing induction on treatment results was also evaluated. We analyzed 125 patients with AML-CK
+
treated within PALG protocols. MK was found in 75 (60%) individuals. The overall complete remission (CR) rate of 66 intensively treated patients was 62% vs. 28% in CK
+
MK
−
and CK
+
MK
+
group (p = .01). No difference in CR rate was observed between DA and DAC arms. The overall survival (OS) in intensively treated patients was negatively influenced by MK, karyotype complexity (≥5 abnormalities), and WBC >20 G/L in multivariate analysis. The addition of cladribine to DA regimen improved OS only in MK
−
but not in MK
+
group. In conclusion, concomitance of MK with ≥5 chromosomal abnormalities is associated with dismal treatment outcome in AMK-CK
+
.
Objectives:Cytogenetics is one of the most important prognostic factors in acute myeloid leukemia (AML). Two major, partially overlapping cytogenetic subsets of AML associated with an adverse ...prognosis, are AML with complex karyotype (CK) and AML with monosomal karyotype (MK). MK has been shown to constitute a cytogenetic feature that identifies AML patients (pts) with very poor outcomes when treated with currently available therapy. CK-AML pts are very heterogeneous cytogenetically, and treatment outcomes of these subsets are also influenced by TP53 alterations, complexity of the karyotype or presence of residual normal metaphases. However, impact of all these variables on outcome of CK-AML patients was so far analyzed separately.
The aim of our study was to assess treatment outcome of CK-AML patients with or without MK regarding some cytogenetic and clinical features.
Materials and methods: One hundred twenty five newly diagnosed AML patients with CK treated between January 2007 and January 2013 with PALG protocols (Holowiecki et al., JCO 2012) were included into the study. Cytogenetic analysis was performed on metaphases from bone marrow aspirates taken at diagnosis using standard banding techniques. Karyotypes were reported in accordance with the ISCN 2009. CK was defined as a presence of ≥ 3 unrelated abnormalities. MK was defined by the presence of an autosomal monosomy in conjunction with at least one other autosomal monosomy or structural abnormality in the absence of t(8;21), inv(16), t(15;17) (Breems et al., JCO 2008). FISH method was used to verify MK in all cases with monosomy as well as to assess 17p13 (TP53) deletion.
Results:Clinical characteristics. The median age of all pts was 60 years (range 19-85 years). FISH verification proved the MK karyotype (MK+) in 75 out of 125 (60%) pts with CK-AML. Remaining pts had non-monosomal CK (MK-). Sixty six (55%) pts received intensive induction chemotherapy (IC) according to PALG protocols and 59 pts received non-intensive treatment with low-dose cytarabine (LDAC) or best supportive care (BSC). Baseline characteristics were generally balanced between MK+ and MK- groups in terms of age, WBC and PLT counts, hemoglobin level, percentage of bone marrow blasts at diagnosis and presence of residual normal metaphases in the karyotype. Higher proportions of MK+ pts had deletion of 17p13 (TP53) (47,9% vs. 20,4% of MK-; p=0.0017) as well as ≥5 cytogenetic aberrations (93,3% vs. 74%; p=0.004). Furthermore, there were no differences in the proportion of IC, LDAC and BSC strategies between both groups.
Treatment Response and Outcome. With the median time of follow-up 7,7 months (mos), median OS in MK- pts was significantly longer compared to MK+ group (4,5 mos vs. 2,0 mos; p=0.0075). 66/125 CK-AML pts received standard IC according to PALG AML protocols (DA-36 pts; DAC-27 pts and DAF-3 pts). Only 7 pts underwent allogeneic stem cell transplantation (allo-SCT). In intensively treated pts the overall CR rate in MK- was about twice as high as in MK+ group (62,1% vs 32,4%; p=0.013). The median OS in MK- pts was longer compared to MK+ group (6,8 mos vs. 2,7 mos; p=0.016). Probability of 1-year OS in MK+ vs. MK- group was 14% vs. 30%. In multivariate analysis we have found that WBC >20 G/l, MK and ≥5 chromosomal abnormalities were independent prognostic factors associated with significantly shorter OS (Table 1). In contrast, allo-SCT was associated with survival benefit. Furthermore, we analyzed the impact of purine analogue containing induction regimens on treatment outcome. We found that addition of cladribine to the standard DA regimen improves OS in MK- but not in MK+ group (Figure 1).
Conclusions: Monosomal karyotype, high WBC count and high complexity of the karyotype (≥5 aberrations) are associated with more aggressive clinical course and short survival in high-risk CK-AML. Cladribine added to standard DA induction regimen prolongs survival of pts with complex but not monosomal karyotype.
*AW and EW equally contributed to the study.
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No relevant conflicts of interest to declare.
The frequency of micronucleated polychromatic erythrocytes in the bone marrow of Swiss mice treated with WR-2721, at a dose of 200 mg/kg or 400 mg/kg body weight, 15 or 30 min prior to ...cyclophosphamide (CP) administration, at a dose of 200 mg/kg body weight, was determined 24 h after CP treatment. In mice injected with CP, the number of micronuclei in polychromatic erythrocytes was significantly increased in comparison with the controls, and in mice treated with WR-2721 and CP, the frequency of micronucleated polychromatic erythrocytes was distinctly decreased in comparison to those given CP alone. The protective effect of WR-2721 against cyclophosphamide-induced clastogenicity was shown. The effect was dependent on the dose of the thiol agent given, and it was more expressed when WR-2721 was applied at the higher dose, 400 mg/kg body weight. However, the protection by the aminothiol appeared not to depend on the time intervals between WR-2721 and CP administration to the mouse organism.
The effect of WR-2721 against cyclophosphamide-induced clastogenicity was studied using the in vivo micronucleus assay. The frequency of micronuclei in polychromatic erythrocytes in the peripheral ...blood of mice treated with WR-2721 and cyclophosphamide (CP), each of the compounds at a dose of 200 mg/kg body weight, was evaluated during the 15-day period. The suppressing effect of WR-2721, given 30 min prior to cyclophosphamide administration, on micronuclei induced by the alkylating agent was demonstrated. The number of micronuclei was increased on day 1 after CP application and declined thereafter with the frequency of micronucleated polychromatic erythrocytes remaining lower in WR-2721 pre-treated mice. The modulatory effect of WR-2721 on the clastogenic activity of cyclophosphamide in the erythropoietic system by the mouse micronucleus test was shown.
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