Correcting artifacts in transition to a wound optic fiber: Example from high-resolution temperature profiling in the Dead Sea

Spatial resolution fiber-optic cables allow for detailed observation of thermally complex heterogeneous hydrologic systems. A commercially produced high spatial resolution helically wound optic fiber sensing cable is employed in the Dead Sea, in order to study the dynamics of thermal stratification of the hypersaline lake. Structured spatial artifacts were found in the data from the first 10 m of cable (110 m of fiber length) following the transition from straight fiber optic. The Stokes and Anti-Stokes signals indicate that this is the result of differential attenuation, thought to be due to cladding losses. Though the overall spatial form of the loss was consistent, the fine structure of the loss changed significantly in time, and was strongly asymmetrical, and thus was not amenable to standard calibration methods. Employing the fact that the cable was built with a duplex construction, and using high-precision sensors mounted along the cable, it was possible to correct the artifact in space and time, while retaining the high-quality of data obtained in the early part of the cable (prior to significant optical attenuation). The defect could easily be overlooked; however, reanalyzing earlier experiments, we have observed the same issue with installations employing similar cables in Oregon and France, so with this note we both alert the community to this persistent concern and provide an approach to correct the data in case of similar problems.Keywords: optic fiber temperature sensing, high-resolution temperature profiling, artifact

High-resolution temperature sensing in the Dead Sea using fiber optics

The thermal stratification of the Dead Sea was observed in high spatial and temporal resolution by means of fiber-optics temperature sensing. The aim of the research was to employ the novel high-resolution profiler in studying the dynamics of the thermal structure of the Dead Sea and the related processes including the investigation of the metalimnion fluctuations. The 18 cm resolution profiling system was placed vertically through the water column supported by a buoy 450 m from shore, from 2 m above to 53 m below the water surface (just above the local seafloor), covering the entire seasonal upper layer (the metalimnion had an average depth of 20 m). Temperature profiles were recorded every 5 min. The May to July 2012 data set allowed quantitative investigation of the thermal morphology dynamics, including objective definitions of key locations within the metalimnion based on the temperature depth profile and its first and second depth derivatives. Analysis of the fluctuation of the defined metalimnion locations showed strong anticorrelation to measured sea level fluctuations. The slope of the sea level versus metalimnion depth was found to be related to the density ratio of the upper layer and the underlying main water body, according to the prediction of a two-layer model. The heat content of the entire water column was calculated by integrating the temperature profiles. The vertically integrated apparent heat content was seen to vary by 50% in a few hours. These fluctuations were not correlated to the atmospheric heat fluxes, nor to the momentum transfer, but were highly correlated to the metalimnion and the sea level fluctuations (r=0.84). The instantaneous apparent heat flux was 3 orders of magnitude larger than that delivered by radiation, with no direct correlation to the frequency of radiation and wind in the lake. This suggests that the source of the momentary heat flux is lateral advection due to internal waves (with no direct relation to the diurnal cycle). In practice, it is shown that snap-shot profiles of the Dead Sea as obtained with standard thermal profilers will not represent the seasonal typical status in terms of heat content of the upper layer.Keywords: High resolution, Metalimnion, Temperature, Thermocline, Dead Se

Allogeneic stem cell transplant in patients with acute myeloid leukemia and karnofsky performance status score less than or equal to 80% : A study from the acute leukemia working party of the European Society for Blood and Marrow Transplantation (EBMT)

Limited data are currently available on the outcome of patients with acute myeloid leukemia (AML) undergoing allogeneic stem cell transplantation (allo-SCT) with a reduced performance status. We herein present the results of a registry study on 2,936 AML patients undergoing allo-SCT in first remission (CR1) with a Karnofsky Performance Status (KPS) score less than or equal to 80%. Two-year leukemia-free survival (LFS), overall survival (OS) and graft-versus-host disease (GVHD)-free, and relapse-free survival (GRFS) rates were 54%, 59%, and 41%, respectively. In multivariable analysis, patients with a KPS score = 80% had lower non-relapse mortality (NRM) and superior OS in comparison to patients with a KPS scorePeer reviewe

Continuously improving outcome over time after second allogeneic stem cell transplantation in relapsed acute myeloid leukemia: an EBMT registry analysis of 1540 patients

Second allogeneic stem cell transplantation (alloSCT2) is among the most effective treatments for acute myeloid leukemia (AML) relapse after first alloSCT (alloSCT1). Long-term EBMT registry data were used to provide large scale, up-to-date outcome results and to identify factors for improved outcome. Among 1540 recipients of alloSCT2, increasing age, better disease control and performance status before alloSCT2, more use of alternative donors and higher conditioning intensity represented important trends over time. Between the first (2000–2004) and last (2015–2019) period, two-year overall and leukemia-free survival (OS/LFS) increased considerably (OS: 22.5–35%, LFS: 14.5–24.5%). Cumulative relapse incidence (RI) decreased from 64% to 50.7%, whereas graft-versus-host disease and non-relapse mortality (NRM) remained unchanged. In multivariable analysis, later period of alloSCT2 was associated with improved OS/LFS (HR = 0.47/0.53) and reduced RI (HR = 0.44). Beyond, remission duration, disease stage and patient performance score were factors for OS, LFS, RI, and NRM. Myeloablative conditioning for alloSCT2 decreased RI without increasing NRM, leading to improved OS/LFS. Haploidentical or unrelated donors and older age were associated with higher NRM and inferior OS. In summary, outcome after alloSCT2 has continuously improved over the last two decades despite increasing patient age. The identified factors provide clues for the optimized implementation of alloSCT2

Complex karyotype but not other cytogenetic abnormalities is associated with worse posttransplant survival of patients with nucleophosmin 1-mutated acute myeloid leukemia:A study from the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party

In the 2022 European LeukemiaNet classification, patients with nucleophosmin 1 (NPM1)-mutated acute myeloid leukemia (AML) were classified in the adverse-risk category in the presence of high-risk cytogenetics (CG). Nonetheless, the impact of various CG aberrations on posttransplant outcomes remains to be unraveled. This registry study analyzed adult patients with NPM1-mutated de novo AML who underwent their first allogeneic hematopoietic cell transplantation in the first complete remission from 2005 to 2021. A total of 3275 patients were identified, 2782 had normal karyotype, 493 had chromosomal aberrations including 160 with adverse-risk CG, 72 patients had complex karyotype (CK), and 66 monosomal karyotype (MK). Overall, 2377 (73%) patients had FLT3-ITD. On univariate analysis, only FLT3-ITD, minimal/measurable residual disease (MRD) positivity and CK, but not abnormal CG, affected posttransplant outcomes. On multivariable analysis, CK was associated with lower overall survival (OS) (hazard ratio [HR] 1.72, p =.009). In the subgroup of 493 patients with aberrant CG, the 2-year leukemia-free survival (LFS) and OS were around 61% and 68%, respectively. On multivariable analysis for this subgroup, CK and MRD positivity were associated with increased risk of relapse (HR 1.7, p =.025; and 1.99, p =.003 respectively) and worse LFS (HR 1.62, p =.018; and 1.64, p =.011 respectively) while FLT3-ITD, MK, or other CG abnormalities had no significant effect. Importantly, CK negatively affected OS (HR 1.91, p =.002). In the first complete remission transplant setting, CK was found as the only cytogenetic risk factor for worse outcomes in NPM1-mutated AML. Nevertheless, even for this subgroup, a significant proportion of patients can achieve long-term posttransplant survival.</p

Measurable residual disease, FLT3-ITD mutation, and disease status have independent prognostic influence on outcome of allogeneic stem cell transplantation in NPM1-mutated acute myeloid leukemia

Nucleophosmin-1 (NPM1) mutations in acute myeloid leukemia (AML) confer a survival advantage in the absence of FLT3-internal tandem duplication (FLT3-ITD). Here, we investigated the main predictors of outcome after allogeneic hematopoietic stem cell transplantation (allo-HCT). We identified 1572 adult (age &gt;= 18 year) patients with NPM1-mutated AML in first complete remission (CR1:78%) or second complete remission (CR2:22%) who were transplanted from matched sibling donors (30.8%) or unrelated donors (57.4%) between 2007 and 2019 at EBMT participating centers. Median follow-up for survivors was 23.7 months. FLT3-ITD was present in 69.3% of patients and 39.2% had detectable minimal/measurable residual disease (MRD) at transplant. In multivariate analysis, relapse incidence (RI) and leukemia-free survival (LFS) were negatively affected by concomitant FLT3-ITD mutation (HR 1.66 p = 0.0001, and HR 1.53, p &lt; 0.0001, respectively), MRD positivity at transplant (HR 2.18, p &lt; 10(-5) and HR 1.71, p &lt; 10(-5), respectively), and transplant in CR2 (HR 1.36, p = 0.026, and HR 1.26, p = 0.033, respectively), but positively affected by Karnofsky score &gt;= 90 (HR 0.74, p = 0.012, and HR 0.7, p = 0.0002, respectively). Overall survival (OS) was also negatively influenced by concomitant FLT3-ITD (HR 1.6, p = 0.0001), MRD positivity at transplant (HR 1.61, p &lt; 10(-5)), and older age (HR 1.22 per 10 years, p &lt; 0.0001), but positively affected by matched sibling donor (unrelated donor: HR 1.35, p = 0.012; haploidentical donor: HR 1.45, p = 0.037) and Karnofsky score &gt;= 90 (HR 0.73, p = 0.004). These results highlight the independent and significant role of FLT3-ITD, MRD status, and disease status on posttransplant outcomes in patients with NPM1-mutated AML allowing physicians to identify patients at risk of relapse who may benefit from posttransplant prophylactic interventions.</p

Machine Learning for Mathematical Software

While there has been some discussion on how Symbolic Computation could be used for AI there is little literature on applications in the other direction. However, recent results for quantifier elimination suggest that, given enough example problems, there is scope for machine learning tools like Support Vector Machines to improve the performance of Computer Algebra Systems. We survey the authors own work and similar applications for other mathematical software. It may seem that the inherently probabilistic nature of machine learning tools would invalidate the exact results prized by mathematical software. However, algorithms and implementations often come with a range of choices which have no effect on the mathematical correctness of the end result but a great effect on the resources required to find it, and thus here, machine learning can have a significant impact.Comment: To appear in Proc. ICMS 201

CNS Involvement at Initial Diagnosis and Risk of Relapse After Allogeneic HCT for Acute Lymphoblastic Leukemia in First Complete Remission

Outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) for adult acute lymphoblastic leukemia (ALL) have improved over time. Studies have shown that total body irradiation (TBI) is the preferable type of myeloablative conditioning (MAC). However, outcomes based on central nervous system (CNS) involvement, namely CNS-positive versus CNS-negative, have not been compared. Here, we evaluated outcomes of 547 patients (CNS-positive = 96, CNS-negative = 451) who were allografted in the first complete remission (CR1) between 2009 and 2019. Primary endpoint was leukemia-free survival (LFS). Median follow-up was not different between the CNS-positive and CNS-negative groups (79 versus 67.2 months, P = 0.58). The CNS-positive group were younger (median age 31.3 versus 39.7 years, P = 0.004) and were allografted more recently (median year 2012 versus 2010, P = 0.003). In both groups, MAC was the preferred approach (82.3% versus 85.6%, P = 0.41). On multivariate analysis, the CNS-positive group had higher incidence of relapse (RI) (hazard ratio [HR] = 1.58 [95% confidence interval (CI) = 1.06-2.35], P = 0.025), but no adverse effect on LFS (HR = 1.38 [95% CI = 0.99-1.92], P = 0.057) or overall survival (OS) (HR = 1.28 [95% CI = 0.89-1.85], P = 0.18). A subgroup multivariate analysis limited to CNS-positive patients showed that a TBI-based MAC regimen resulted in better LFS (HR = 0.43 [95% CI = 0.22-0.83], P = 0.01) and OS (HR = 0.44 [95% CI = 0.21-0.92], P = 0.03) and lower RI (HR = 0.35 [95% CI = 0.15-0.79], P = 0.01). Another subgroup analysis in CNS-negative patients showed that MAC-TBI preparative regimens also showed a lower RI without a benefit in LFS or OS. While a MAC-TBI allo-HCT regimen may not be suitable to all, particularly for older patients with comorbidities, this approach should be considered for patients who are deemed fit and able to tolerate.Peer reviewe