Conventional Stratification Research Articles

Calibrated Empirical Neutrosophic Cumulative Distribution Function Estimation for Both Symmetric and Asymmetric Data

The traditional stratification weight is widely used in survey sampling for estimation under stratified random sampling (StRS). A neutrosophic calibration approach is proposed under neutrosophic statistics for the first time with the aim of improving conventional stratification weight. This addresses the challenge of estimating the empirical cumulative distribution function (CDF) of a finite population using the neutrosophic technique. The neutrosophic technique extends traditional statistics, dealing with indeterminate, vague, and uncertain values. Thus, using additional information, we are able to obtain an effective estimate of the neutrosophic CDF. The suggested estimator yields an interval range in which the population empirical CDF is likely to exist rather than a single numerical value. The proposed family of neutrosophic estimators will be defined under suitable calibration constraints. A simulation study is also computed in order to assess the effectiveness of the suggested and adapted neutrosophic estimators using real-life symmetric and asymmetric datasets.

Stratified predictions of upper limb motor outcomes after stroke.

Longitudinal observations of upper limb motor recovery after stroke have suggested that certain subgroups may exhibit distinct recovery patterns. Here we sought to examine whether the predictive ability for post-stroke upper limb motor outcomes could be enhanced by applying conventional stratification strategies. For 60 individuals who suffered the first stroke, upper limb motor impairment was assessed with the upper extremity Fugl-Meyer assessment (UE-FMA) at 2 weeks as a baseline and then 3 months post-stroke. Brain structural damage at baseline was assessed by MRI data-derived markers ranging from traditional lesion size to the lesion load and to the disconnectome. Linear regression models for predicting upper limb motor outcomes (UE-FMA score at 3 months post-stroke) based on baseline upper limb motor impairment (UE-FMA score at 2 weeks post-stroke), brain structural damage, and their combinations were generated, and those with the best predictive performance were determined for individual subgroups stratified according to initial impairment (severe and non-severe), lesion location (cortical and non-cortical), and neurophysiological status (motor evoked potential-positive and motor evoked potential-negative). The best predictions were made by baseline upper limb motor impairment alone for subgroups with less functional impairment (non-severe) or less structural involvement (non-cortical), but by the combination of baseline upper limb motor impairment and brain structural damage for the other subgroups. The predictive models tailored for subgroups determined according to initial impairment and neurophysiological status yielded a smaller overall error than that for the whole group in upper limb motor outcome predictions. The predictive ability for upper limb motor outcomes could be enhanced beyond the one-size-fits-all model for all individuals with stroke by applying specific stratification strategies, with stratification according to initial impairment being the most promising. We expect that predictive models tailored for individual subgroups could lead closer to the personalized prognosis of upper limb motor outcomes after stroke.

Prediction of thrombosis in polycythemia vera: Development and validation of a multiple factor-based prognostic score system

BackgroundThrombosis is an important cause of death in patients with polycythemia vera (PV). The conventional stratification of thrombosis may ignore some potential risk factors. ObjectivesThis study aimed to develop and validate a multiple factor-based prediction model of thrombosis for the 2016 World Health Organization-dened PV. MethodsClinical and next-generation sequencing data from 2 cohorts of patients with PV were analyzed. Multivariable Cox regression analyses were conducted for the identification of thrombotic risk factors and model development. ResultsThe study involved 372 patients in the training cohort and another 195 patients in the external validation cohort. Multivariable analyses indicated that age ≥60 years (hazard ratio [HR] 2.56, 95% CI 1.51-4.35, P < .001), cardiovascular risk factors (HR 4.22, 95% CI 2.00-8.92, P < .001), at least 1 high-risk mutation for thrombosis (mutations in DNMT3A, ASXL1, or BCOR/BCORL1) (HR 4.35, 95% CI 2.62-7.21, P < .001), and previous thrombosis (HR 5.93, 95% CI 3.29-10.68, P < .001) were independent risk factors of thrombosis. After assigning coefficient-weighted scores to each risk factor mentioned above, a multiple factor-based prognostic score system of thrombosis (MFPS-PV) was developed, classifying patients into low-risk, intermediate-risk, and high-risk groups. Patients in the 3 groups had notably different thrombosis-free survival rates (P < .001). The MFPS-PV outperformed the conventional model in discrimination power (C-statistic: 0.87 [95% CI 0.83-0.91] vs 0.80 [95% CI 0.74-0.86]). The MFPS-PV was well calibrated and remained consistent during external validation. ConclusionThe MFPS-PV, integrating genetic and clinical characteristics for the first time, shows excellent accuracy and utility for thrombosis prediction in WHO-defined PV.

The Immunological Contribution of a Novel Metabolism-Related Signature to the Prognosis and Anti-Tumor Immunity in Cervical Cancer.

Simple SummaryCervical cancer is the most commonly diagnosed gynecological malignant carcinoma worldwide. It is crucial to develop reliable prognostic models to predict clinical outcomes and identify patients who will benefit from different treatment strategies. In current study, we identified a reliable metabolism-related signature composed of ALOX12B, CA9, FAR2, F5 and TDO2 for the prognosis and anti-tumor immunity in cervical cancer. Patients with high-risk score underwent apparently worse prognosis and displayed lower infiltration of tumor infiltrating lymphocytes. Additionally, the metabolism-based risk score could also predict the prognosis of patients with cervical cancer based on the expression of immune checkpoints. Since this risk score signature achieves a good performance in predicting clinical outcome, we genuinely expect that our study could provide an effective prognostic tool for guidance of personalized treatment of cervical cancer patients.Cervical cancer is the most frequently diagnosed malignancy in the female reproductive system. Conventional stratification of patients based on clinicopathological characters has gradually been outpaced by a molecular profiling strategy. Our study aimed to identify a reliable metabolism-related predictive signature for the prognosis and anti-tumor immunity in cervical cancer. In this study, we extracted five metabolism-related hub genes, including ALOX12B, CA9, FAR2, F5 and TDO2, for the establishment of the risk score model. The Kaplan-Meier curve suggested that patients with a high-risk score apparently had a worse prognosis in the cervical cancer training cohort (TCGA, n = 304, p < 0.0001), validation cohort (GSE44001, n = 300, p = 0.0059) and pan-cancer cohorts (including nine TCGA tumors). Using a gene set enrichment analysis (GSEA), we observed that the model was correlated with various immune-regulation-related pathways. Furthermore, pan-cancer cohorts and immunohistochemical analysis showed that the infiltration of tumor infiltrating lymphocytes (TILs) was lower in the high-score group. Additionally, the model could also predict the prognosis of patients with cervical cancer based on the expression of immune checkpoints (ICPs) in both the discovery and validation cohorts. Our study established and validated a metabolism-related prognostic model, which might improve the accuracy of predicting the clinical outcome of patients with cervical cancer and provide guidance for personalized treatment.

Carbon Monoxide Diffusion Capacity as a Severity Marker in Pulmonary Hypertension

Carbon monoxide diffusion capacity (DLCO) is negatively associated with patient survival in idiopathic pulmonary hypertension (PH), but is not included in the risk stratification score proposed by the 2015 European guidelines. Since 2015, several new stratification scores based on a 3- or 4-severity scale have been explored. This retrospective cohort single-center study sought to investigate the association between DLCO and PH severity and survival. We included 85 treatment-naive patients with precapillary PH and DLCO measurement at diagnosis. DLCO status, based on lower and upper quartiles ranges, was added to a 3- and a 4-strata modified-risk assessment. DLCO was strongly associated with transplant-free survival (HR 0.939, 95% CI: 0.908–0.971, p < 0.001). In the intermediate and high-risk categories, DLCO was associated with transplant-free survival, irrespective of the risk category (HR 0.934, 95% CI: 0.880–0.980, p = 0.005). The correlation between modified-risk category and transplant-free survival was significant (HR 4.60, 95% CI: 1.294–16.352, p = 0.018). Based on the Akaike information criterion (AIC) levels, the 3- and 4-strata modified-risk stratification fits our results better than the conventional stratification. Low DLCO is associated with patient transplant-free survival, independently of the risk category. Inclusion of DLCO into a PH risk stratification score seems promising and needs further investigation.

Predicting Dynamic Clinical Outcomes of the Chemotherapy for Canine Lymphoma Patients Using a Machine Learning Model.

First-line treatments of cancer do not always work, and even when they do, they cure the disease at unequal rates mostly owing to biological and clinical heterogeneity across patients. Accurate prediction of clinical outcome and survival following the treatment can support and expedite the process of comparing alternative treatments. We describe the methodology to dynamically determine remission probabilities for individual patients, as well as their prospects of progression-free survival (PFS). The proposed methodology utilizes the ex vivo drug sensitivity of cancer cells, their immunophenotyping results, and patient information, such as age and breed, in training machine learning (ML) models, as well as the Cox hazards model to predict the probability of clinical remission (CR) or relapse across time for a given patient. We applied the methodology using the three types of data obtained from 242 canine lymphoma patients treated by (L)-CHOP chemotherapy. The results demonstrate substantial enhancement in the predictive accuracy of the ML models by utilizing features from all the three types of data. They also highlight superior performance and utility in predicting survival compared to the conventional stratification method. We believe that the proposed methodology can contribute to improving and personalizing the care of cancer patients.

Effect of three different veneering techniques on the stress distribution and in vitro fatigue behavior of core-veneer all-ceramic fixed partial dentures.

Background. The present study aimed to evaluate the influence of the veneering technique on the tensile stress distribution and survival of full-ceramic fixed dental prostheses (FDPs). Methods. A three-dimensional model of an FDP was modeled on a second premolar and a second molar with a pontic between them for finite element analysis (FEA). The groups were divided according to the veneering technique: conventional stratification, rapid layer, and CAD-on techniques. A mesh control test determined the number of elements and nodes. The materials’ properties were attributed to each solid component with isotropic, homogeneous, and linear elastic behavior. For the in vitro fatigue test (n=30), the FDPs were cemented on dentin analog abutments and submitted to 2×106 mechanical cycles (100 N at 3 Hz). Results. Maximum principal stress showed that the connector between the pontic and the second molar concentrated higher stresses, regardless of the techniques: Rapid layer (6 MPa) > CAD-on (5.5 MPa) > conventional stratification (4 MPa). The conventional stratification technique concentrated high stresses at the interface between the framework and veneering ceramic (2 MPa), followed by the rapid layer (1.8 MPa) and CAD-on (1.5 MPa) techniques. The crowns fabricated using the rapid layer and CAD-on techniques exhibited a 100% survival rate, while the conventional stratification group had 0% survival. Conclusion. Even with similar stress distribution between the veneering techniques, the conventional stratification technique was more prone to failure under fatigue due to higher defects incorporated than CAD-on and rapid layer techniques.

The rise of China and its impact on world economic stratification and re-stratification

The article provides a framework for understanding the historical trajectory of China’s rise and its impact on the conventional stratification of the capitalist world-economy of the core, semi-periphery and periphery. Inspired by World-System Theory, the author analyses the process through which China’s global economic rise is challenging the status quo of the world-economy’s established structure. In other words, China’s economic rise is modifying the ‘classical’ stratification of the world economic zones as conceptualised by World-System Theory in terms of the core, semi-peripheral and peripheral relationships and in terms of the composition and proportional size of the three economic zones. As a result, the conventional stratification of a small core, a scattered larger semi-periphery and a vast periphery is being altered. The article goes through China’s different positions in the world’s economic stratification during different periods, and concludes that the global transformations led by China’s economic rise is leading the world towards a regional and global re-division of labour, which is exerting a great deal of impact on both the Global North and the Global South in terms of opportunities and challenges.

Advanced Ultrasound Application - Impact on Presurgical Risk Stratification of the Thyroid Nodules.

AimCurrent major guidelines recommend risk stratification of the thyroid nodules, after each diagnostic evaluation, in order to focus attention on potentially risky nodules. The main aim of our study was to evaluate the performance of combined advanced ultrasound techniques in this process, compared with conventional stratification models, in order to reduce unnecessary fine-needle biopsies, respectively, surgery.Material and MethodsWe evaluated 261 cases (261 nodules) using conventional ultrasound (2B), real-time Doppler evaluation (4D) respectively, real-time elastography, using a linear multifrequency probe and a linear volumetric probe (Hitachi Prerius Machine, Hitachi Inc, Japan). All the nodules were classified using a risk stratification model comprising seven conventional US characteristics, two 4 D characteristics and a color map RTE aspect. The results were compared with the pathology results, considered the golden standard diagnosis.ResultsThe prevalence of malignant nodules was 21.83% (57 cases). Conventional risk classification generated: 106 low-risk cases, 113 intermediate-risk and 42 high-risk cases. Our proposed risk classification changes the conventional risk classification with a risk upgrade in 27 cases and with a risk downgrade in 69 cases. The diagnostic quality of the combined risk stratification model was better, considering a low-risk category predictive for benignancy and a high category predictive for malignancy: Sensitivity: 80.88% versus 49.01%, respectively, Specificity: 91.22% versus 54.38. The diagnostic power differences were observed regardless of the nodule size.ConclusionAdvanced ultrasound techniques did add diagnostic value in the presurgical risk assessment of the thyroid nodules.

Design of Groundwater Extraction in Open Cut Foundation Pit and Simplified Calculation of Ground Subsidence due to Dewatering in Sandy Pebble Soil Strata

In order to study the design of incomplete well point for groundwater extraction in open cut foundation pit in which the inner and outer aquifers are not completely isolated and the change mechanism of ground subsidence due to dewatering in the foundation pit, an open cut foundation pit for a subway station on Chengdu Metro Line 6 is taken as an example; meanwhile, the typical sandy pebble soil strata are also considered as a research object in this paper. Firstly, a new method for designing groundwater extraction in the open cut foundation pit is presented and applied to the practical project. The dewatering funnel curve is derived based on Dupuit’s assumption, and the ground subsidence around the foundation pit due to groundwater extraction is calculated using the stratification summation method as well as considering the effect of seepage force. The finite difference software FLAC3D is employed to simulate the groundwater extraction process in the foundation pit, and the simulation of groundwater extraction by single well point and group well points is also carried out and the unapparent effect of group well points is obtained. The comparison among on‐site monitoring, theoretical calculation, and numerical simulation shows that these values have the same trend in indicating ground subsidence, and the conventional stratification summation method is conservative, and the algorithm considering the effect of seepage force is more accurate. Therefore, the ground subsidence curve caused by groundwater extraction in the foundation pit is presented. The above research methods and results can be applicable for practical engineering and be used to guide the design and construction of groundwater extraction in the foundation pit by using the open cut method in sandy pebble soil strata.

Prognostic Significance of Preoperative Neutrophil-to-Lymphocyte Ratio in Surgically Resectable Pancreatic Neuroendocrine Tumors.

BackgroundThe aim of this study was to evaluate the predictive and prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in pancreatic neuroendocrine tumor (PNET) patients undergoing potentially curative resection.Material/MethodsA retrospective review of 172 patients with PNETs was conducted. Kaplan-Meier curves and multivariate Cox proportional models were used to calculate overall survival (OS) and disease-free survival (DFS). The predictive performance of the NLR was compared with other inflammation-based scores and conventional stratification systems using receiver operating characteristic (ROC) curve analysis.ResultsElevated NLR and PLR were both associated with advanced AJCC stage and high grade. In the univariate analysis, elevated NLR and PLR were both significantly associated with decreased OS and DFS. In the multivariate analysis, the preoperative NLR, but not the PLR, was an independent risk factor for OS (HR=4.471, 95% CI 1.531–13.054, p=0.006) and DFS (HR=2.531, 95% CI 1.202–5.329, p=0.015). The discriminatory capability of the NLR was superior to that of other inflammation-based scores in OS prediction. Furthermore, the predictive range was expanded by incorporating the NLR into the conventional stratification systems, including the AJCC stage and WHO classification systems.ConclusionsAs an independent prognostic factor, an elevated preoperative NLR is superior to the PLR with respect to predicting clinical outcomes in PNET patients undergoing potentially curative resection. The incorporation of the NLR into the existing conventional stratification systems improved the predictive accuracy.

Prognostic significance of preoperative gamma-glutamyltransferase to lymphocyte ratio index in nonfunctional pancreatic neuroendocrine tumors after curative resection

Various inflammation-based prognostic scores have been associated with reduced survival in patients with nonfunctional pancreatic neuroendocrine tumor (NF-PNET). However, few studies have illuminated the relationship between the preoperative gamma-glutamyltransferase (GGT) to lymphocyte ratio index (GLRI) and the prognosis of NF-PNET. A retrospective review of 125 NF-PNET patients following curative resection was conducted. The cut-off values for the inflammation-based prognostic scores, including GLRI, were selected using receiver operating characteristic curve analysis. Univariate, multivariate and Kaplan-Meier analyses were used to calculate overall survival (OS) and disease-free survival (DFS). The optimal cut-off value for GLRI was 10.3. Multivariate analysis showed that GLRI was an independent predictor of OS (P = 0.001) and DFS (P = 0.007) for NF-PNET. Kaplan-Meier analysis also showed that preoperative GLRI had significant prognostic value in various subgroups of patients with NF-PNET. The discriminatory capability of GLRI was superior to that of other inflammation-based scores in OS prediction. Furthermore, the predictive range was expanded by incorporating GLRI into the conventional stratification systems, including AJCC staging and WHO classification. These results indicated that preoperative GLRI was an independent predictor for NF-PNET patients undergoing curative resection. The incorporation of GLRI into the existing conventional stratification systems resulted in improved predictive accuracy.

Measurement of Serum EGF Levels, a Methodological Approach: Learning What Means “Low-/High-Concentration of EGF In Serum”. Some Clinical Implications

Background: Although the contribution of platelets to the measured serum EGF levels was reported by Oka since 1983, the majority of reports in healthy donors or patients do not control clotting times during the collection of the sera. This results in a variation of the notified values, additionally to the one already caused by the functional EGF SNP of the gene, that modulates the expression of the molecule. Both issues -platelets and SNP- make the conventional stratification by absolute serum EGF levels not suitable. Within this study we evaluated serum EGF levels in a panel of 105 healthy Cuban donors, balanced by gender and age (from 18-78 years). As a result, a new stratification methodology for the comparison between individuals was proposed. Methods: The EGF was estimated in sera collected at two different clotting times: 1h and 4h. Comparisons between groups were carried out. The estimations, normalized through the calculation of ratios from the two measured levels (r=[EGF]1h/[EGF]4h), were used for the stratification. Results: Differences were found by age (4h, donors younger and older than 45 years, p=0.0083) and gender (1h, p=0.0167), and between 1h and 4h levels (p<0.0001, n=105). While 38 out of 105 individuals ranked different in 1h and 4h conventional stratifications, the methodology using ratios yielded a unique score for each individual. Conclusions: The proposed methodology of stratification by ratios, in contrast to the conventional approach, allows for a proper comparison between EGF levels and individuals. Thus, it should have an impact on diseases for which the association of EGF with the illness has been established, aiding to clarify the connection of the molecule with the disease. This work might be of value to clinicians, scientists, and the healthcare community in general, conducting research regarding the role of EGF as a biomarker.

Targeted next generation sequencing of endoscopic ultrasound acquired cytology from ampullary and pancreatic adenocarcinoma has the potential to aid patient stratification for optimal therapy selection.

Background & AimsLess than 10% of registered drug intervention trials for pancreatic ductal adenocarcinoma (PDAC) include a biomarker stratification strategy. The ability to identify distinct mutation subsets via endoscopic ultrasound fine needle aspiration (EUS FNA) molecular cytology could greatly aid clinical trial patient stratification and offer predictive markers. We identified chemotherapy treatment naïve ampullary adenocarcinoma and PDAC patients who underwent EUS FNA to assess multigene mutational frequency and diversity with a surgical resection concordance assessment, where available.MethodsFollowing strict cytology smear screening criteria, targeted next generation sequencing (NGS) using a 160 cancer gene panel was performed.ResultsComplete sequencing was achieved in 29 patients, whereby 83 pathogenic alterations were identified in 21 genes. Cytology genotyping revealed that the majority of mutations were identified in KRAS (93%), TP53 (72%), SMAD4 (31%), and GNAS (10%). There was 100% concordance for the following pathogenic alterations: KRAS, TP53, SMAD4, KMT2D, NOTCH2, MSH2, RB1, SMARCA4, PPP2R1A, PIK3R1, SCL7A8, ATM, and FANCD2. Absolute multigene mutational concordance was 83%. Incremental cytology smear mutations in GRIN2A, GATA3 and KDM6A were identified despite re-examination of raw sequence reads in the corresponding resection specimens.ConclusionsEUS FNA cytology genotyping using a 160 cancer gene NGS panel revealed a broad spectrum of pathogenic alterations. The fidelity of cytology genotyping to that of paired surgical resection specimens suggests that EUS FNA represents a suitable surrogate and may complement the conventional stratification criteria in decision making for therapies and may guide future biomarker driven therapeutic development.

Disparities in earnings and education in India

AbstractThis paper studies the impact of different levels of education, religion, caste as well as the impact of living in urban and rural communities on earnings in India. Besides these conventional stratification, yet another academic caste which influence earnings—the English language ability, is also examined. The paper uses a large cross-section sample of India Human Development Survey to estimate Mincer and augmented Mincer equations. The rates of return estimates obtained in these data and method confirm that returns to education increase with the level of education across location, caste-religion and English language ability. Returns to lower levels of education are low across different groups, indicating the low quality of basic schooling in the country. Returns to higher education vary at a great deal ranging between 4.9% among the rural workers and 38.2% among fluent English ability group. This is in contrast to Duraisamy reporting the highest returns to secondary education in India, between th...

Prediction of Outcome by Early Response in Childhood Acute Lymphoblastic Leukemia

In the ALL-BFM studies for treatment of acute lymphoblastic leukemia, reduction of leukemic blasts in peripheral blood after a one-week prednisone pre-phase - the so-called prednisone response - has been used for risk stratification since the 1980s and has been one of the most relevant factors for identification of high-risk patients. In the trial ALL-BFM 95, early cytomorphological marrow response on day 15 of induction therapy was prospectively evaluated and its prognostic value was analyzed in comparison to the prednisone response and other established prognostic factors. Compared to prednisone response, day 15 marrow response was superior in outcome prediction - yet with differential effect depending on blast lineage. Outcome was poor in T cell leukemia patients with prednisone poor-response independent of day 15 marrow response, whereas among patients with prednisone good-response different risk groups could be identified by day 15 marrow response. In contrast, prednisone response lost prognostic significance in precursor B cell leukemia when stratified by day 15 marrow response. Selective addition of day 15 marrow response to conventional stratification criteria applied on ALL-BFM 95 may significantly improve risk-adapted treatment delivery. Even though cutting-edge trial risk stratification is meanwhile dominated by minimal residual disease evaluation, an improved conventional risk assessment, as presented here, could be of great importance to countries lacking the technical and/or financial resources associated with the application of minimal residual disease analysis.

Stratified Sampling Design Based on Data Mining

ObjectivesTo explore classification rules based on data mining methodologies which are to be used in defining strata in stratified sampling of healthcare providers with improved sampling efficiency.MethodsWe performed k-means clustering to group providers with similar characteristics, then, constructed decision trees on cluster labels to generate stratification rules. We assessed the variance explained by the stratification proposed in this study and by conventional stratification to evaluate the performance of the sampling design. We constructed a study database from health insurance claims data and providers' profile data made available to this study by the Health Insurance Review and Assessment Service of South Korea, and population data from Statistics Korea. From our database, we used the data for single specialty clinics or hospitals in two specialties, general surgery and ophthalmology, for the year 2011 in this study.ResultsData mining resulted in five strata in general surgery with two stratification variables, the number of inpatients per specialist and population density of provider location, and five strata in ophthalmology with two stratification variables, the number of inpatients per specialist and number of beds. The percentages of variance in annual changes in the productivity of specialists explained by the stratification in general surgery and ophthalmology were 22% and 8%, respectively, whereas conventional stratification by the type of provider location and number of beds explained 2% and 0.2% of variance, respectively.ConclusionsThis study demonstrated that data mining methods can be used in designing efficient stratified sampling with variables readily available to the insurer and government; it offers an alternative to the existing stratification method that is widely used in healthcare provider surveys in South Korea.

Has MRD monitoring superseded other prognostic factors in adult ALL?

Significant improvements have been made in the treatment of acute lymphoblastic leukemia (ALL) during the past 2 decades, and measurement of submicroscopic (minimal) levels of residual disease (MRD) is increasingly used to monitor treatment efficacy. For a better comparability of MRD data, there are ongoing efforts to standardize MRD quantification using real-time quantitative PCR of clonal immunoglobulin and T-cell receptor gene rearrangements, real-time quantitative-based detection of fusion gene transcripts or breakpoints, and multiparameter flow cytometric immunophenotyping. Several studies have demonstrated that MRD assessment in childhood and adult ALL significantly correlates with clinical outcome. MRD detection is particularly useful for evaluation of treatment response, but also for early assessment of an impending relapse. Therefore, MRD has gained a prominent position in many ALL treatment studies as a tool for tailoring therapy with growing evidence that MRD supersedes most conventional stratification criteria at least for Ph-negative ALL. Most study protocols on adult ALL follow a 2-step approach with a first classic pretherapeutic and a second MRD-based risk stratification. Here we discuss whether and how MRD is ready to be used as main decisive marker and whether pretherapeutic factors and MRD are really competing or complementary tools to individualize treatment.

Prediction of outcome by early bone marrow response in childhood acute lymphoblastic leukemia treated in the ALL-BFM 95 trial: differential effects in precursor B-cell and T-cell leukemia

In the ALL-BFM 95 trial for treatment of acute lymphoblastic leukemia, response to a prednisone pre-phase (prednisone response) was used for risk stratification in combination with age and white blood cell count at diagnosis, response to induction therapy and specific genetic high-risk features. Cytomorphological marrow response was prospectively assessed on Day 15 during induction, and its prognostic value was analyzed in 1,431 patients treated on ALL-BFM 95. The 8-year probabilities of event-free survival were 86.1%, 74.5%, and 46.4% for patients with M1, M2, and M3 Day 15 marrows, respectively. Compared to prednisone response, Day 15 marrow response was superior in outcome prediction in precursor B-cell and T-cell leukemia with, however, a differential effect depending on blast lineage. Outcome was poor in T-cell leukemia patients with prednisone poor-response independent of Day 15 marrow response, whereas among patients with prednisone good-response different risk groups could be identified by Day 15 marrow response. In contrast, prednisone response lost prognostic significance in precursor B-cell leukemia when stratified by Day 15 marrow response. Age and white blood cell count retained their independent prognostic effect. Selective addition of Day 15 marrow response to conventional stratification criteria applied on ALL-BFM 95 (currently in use in several countries as regular chemotherapy protocol for childhood acute lymphoblastic leukemia) may significantly improve risk-adapted treatment delivery. Even though cutting-edge trial risk stratification is meanwhile dominated by minimal residual disease evaluation, an improved conventional risk assessment, as presented here, could be of great importance to countries that lack the technical and/or financial resources associated with the application of minimal residual disease analysis.

VERMICULITE IMPROVES EARLY DEVELOPMENT AND SURVIVAL OF LOW CHILL STONE-FRUIT EMBRYOS RESCUED IN VITRO

There are many reports of efficient embryo germination and the method has been optimized to suit subtropical low chill genotypes. However the subsequent growth, vigor, and ability of germinated embryos to develop and survive acclimatization is rarely reported. Many germinated embryos do not survive acclimatization, develop slowly, or fail to develop normally. Methods to improve plant development from in vitro embryo cultures are needed to improve the number of plants that survive to be useful in breeding programs. This paper describes an improved method of embryo rescue that significantly increases embryo shoot and root development that leads to increased plant survival. Four treatments: Woody Plant Media (WPM) solidified with agar, vermiculite with liquid WPM, vermiculite with WPM plus agar, and conventional stratification, were evaluated for embryo growth and subsequent plantlet development and survival for two low-chill peach and one low-chill nectarine cultivar. Highly significant improvements were found for shoot and root development of seedlings germinated in vermiculite based media compared to embryos germinated in conventional agar-based media. Vermiculite with WPM and agar improved plantlet growth subsequent to in vitro culture and significantly increased survival of germinated embryos resulting in more plants reaching the field.