Journal articles on the topic 'Discordant colour'
To see the other types of publications on this topic, follow the link: Discordant colour.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Discordant colour.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Mancuso, Patrizia, Elisabetta Muratori, Cristina Rabascio, Angelica Calleri, Chiara Corsini, and Francesco Bertolini. "Lymphoma Cell Detection and Follow-Up in the Rituximab Era: Concordance between Flow Cytometry, Qualitative/Quantitative PCR and FISH in the Marrow and Blood from 647 Patients." Blood 104, no. 11 (November 16, 2004): 1376. http://dx.doi.org/10.1182/blood.v104.11.1376.1376.
Full textAbstract:
Abstract The anti-CD20 monoclonal antibody Rituximab is now widely used in B-cell non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL) patients. Its administration is associated with a profound reduction of the number of normal and malignant CD20+ B cells, so that the procedures used so far for NHL and CLL diagnosis, detection of minimal residual disease (MRD) and follow-up (F-UP) should be revised. We have retrospectively evaluated our consecutive 4-year record of 647 NHL and CLL patients. Our aims were: 1) to compare sensitivity and concordance between 4-colour flow cytometry, qualitative and quantitative PCR and FISH. 2) to compare concordance between bone marrow (BM) and peripheral blood (PB). Sensitivity of the procedures (evaluated by serial dilution of NHL cell lines in healthy donors’ BM and PB) were found to be 10−5, 10−6, 10−4/5 and 10−3 for 4-colour flow cytometry, qualitative PCR, quantitative PCR and FISH, respectively. A total of 955 paired BM and PB samples were investigated. Most frequent diagnoses were follicular NHL (29%), diffuse large B-cell NHL (22%), marginal zone NHL (11%), CLL (10%), and mantle cell NHL (8%). In 236/955 cases (25%), 4-color flow cytometry identified a monoclonal or a phenotypically aberrant cell population. Concordance between BM and PB was 87% (p<0.001). Most frequent diagnosis of discordant cases was lymphoplasmocytoid-Waldenstrom NHL (36% of discordant cases). Qualitative and quantitative PCR were used to investigate clonality (Fr2A/VLJH and Fr2A/VLJH genes) and the presence of translocations involving BCL-1 or BCL-2 genes (in mantle cell or follicular NHL, respectively). A total of 91/333 samples (27%) were positive. Concordance between BM and PB was 91% (p<0.001). Discordance was found in 11% of mantle cells NHL and 8% of follicular NHL cases. When 118 patients were evaluated 3-month after Rituximab (alone or in combination with chemotherapy), qualitative PCR still detected malignant cells in 95% of previously PCR-positive patients, flow cytometry in 72% of previously cytometry-positive patients. On the other hand, at 7 month after Rituximab, in these patients malignant cells were found by qualitative PCR in 14/72 (19%) cases, by flow-cytometry in 22/118 (19%) cases. These procedures identified disease persistence or recurrence significantly earlier than quantitative PCR (evaluated in 98 cases, p<0.01) and FISH (evaluated in 11 cases, p<0.001). We conclude that 1) BM and PB examination by means of 4-color flow cytometry and qualitative PCR offer nearly-overlapping results. In Rituximab-treated patients, differences seen at 3-month F-UP, probably due to the higher sensitivity of qualitative PCR, are no more observed at 7-month F-UP. 2) Four-color flow cytometry and qualitative PCR have higher sensitivity and detect MRD and relapses significantly earlier than quantitative PCR and FISH. 3) With the exception of lymphoplasmocytoid-Waldenstrom NHL, PB examination may be considered a sensitive and specific alternative to BM examination in NHL and CLL patients, including those treated with Rituximab.
2
Mano, Pavan. "Disarming as a tactic of resistance in Pink Dot." Pink Dot 10, no. 2 (July 16, 2021): 129–56. http://dx.doi.org/10.1075/jls.20008.man.
Full textAbstract:
Abstract Pink Dot is an annual rally in support of LGBT (lesbian, gay, bisexual, and transgender) people in Singapore. In a country where many prefer to avoid overt displays of dissent, Pink Dot has gained significant popular support. In this article, I explore how it has done so. Through a close multimodal analysis focusing on the use of colour, layout, and typography in a Pink Dot 2017 flyer, I demonstrate how these features work together in the Singaporean context to realize meanings of positivity, warmth, and inclusivity whilst simultaneously de-emphasizing notions of claiming rights. I argue Pink Dot discursively attenuates the potentially discordant elements of its message and marshals this apparent neutrality to gather support for its ostensibly depoliticized message – a process that I term disarming. It is an assimilationist strategy deliberately made for Singapore’s particular sociopolitical context and it has proven effective in securing mass popular support amongst Singaporeans.
3
Beck, O., M. Kraft, M. R. Moeller, B. L. Smith, S. Schneider, and R. Wennig. "Frontline ® immunochromatographic device for on-site urine testing of amphetamines: laboratory validation using authentic specimens." Annals of Clinical Biochemistry: International Journal of Laboratory Medicine 37, no. 2 (March 1, 2000): 199–204. http://dx.doi.org/10.1258/0004563001899005.
Full textAbstract:
We evaluated a new test device for amphetamines and methamphetamines (Frontline ®, cut-off limit 300 ng/mL) using authentic clinical and forensic specimens. The device is based on immunochromatography and is dipped into urine and read visually by comparison with a colour scale after a few minutes. A total of 658 specimens were tested by comparing results of the screening procedure with established immunoassays. Discordant results were further investigated by gas chromatography- mass spectrometry or gas chromatography (with flame ionization detector). The Frontline device had a sensitivity of 93% and a specificity of 98%. When specimens were classified by urine amphetamine concentration, close agreement was obtained at concentrations below 150 ng/mL and above 1000 ng/mL. A small number of specimens with amphetamine concentrations between 300 and 1000 ng/mL tested negative in the Frontline test. This finding could to some extent be explained by the enantioselectivity of the antibodies in the Frontline test to d-amphetamine. We conclude that the performance of the Frontline test device for amphetamines is adequate for presumptive clinical and forensic screening.
4
Kröber, Alexander, Dirk Kienle, Dirk Winkler, Andreas Bühler, Till Seiler, Christine Schöpflin, Sabrina Kless, Claire Paulus, Hartmut Döhner, and Stephan Stilgenbauer. "ZAP-70 Expression, VH-Mutation Status, Genomic Aberrations and Prognosis in Chronic Lymphocytic Leukemia." Blood 104, no. 11 (November 16, 2004): 1920. http://dx.doi.org/10.1182/blood.v104.11.1920.1920.
Full textAbstract:
Abstract The VH status is a strong prognostic marker in chronic lymphocytic leukemia (CLL). ZAP-70, a zeta associated tyrosine kinase physiologically expressed by T-cells, is overexpressed in VH unmutated CLL and could therefore serve as a surrogate marker for the VH status. We analyzed ZAP-70 expression (n=96), the VH status (n=75) and genomic aberrations (n=84) in a single center CLL cohort to study associations among these parameters and to assess their relative prognostic value. ZAP-70 expression was measured by 4-colour flow cytometry (CD5, CD19, CD3/56, ZAP-70) applying an unconjugated anti-ZAP-70-antibody (Upstate, clone 2F3.2) according to Crespo et al., NEJM 2003. ZAP-70 expression was positive (cut-off 20%) in 67% and negative in 33% of cases. VH was mutated in 33% and unmutated in 67% of cases. Unfavorable genomic aberrations (17p−, 11q−) were more frequently observed in cases with unmutated VH (46 vs. 9%) and in ZAP-70 positive cases (39 vs. 20%), while favorable genomic aberrations (13q− as single aberration) occurred more frequently in VH mutated (48 vs. 17%) and ZAP-70 negative subgroups (50 vs. 18%). ZAP-70 expression predicted the VH status in 84% of cases. At a median follow up time of 47 months (m), the median treatment free survival (TFS) of ZAP-70 positive and negative cases was 31 and 86 m (p=.057). The median TFS of the VH unmutated and VH mutated subgroups were 24 and 172 m (p<.001). Within the follow up time 10 deaths occurred. Of these, 8 cases exhibited high ZAP-70 expression and an unmutated VH, whereas 2 cases showed discordant results. Overall, discordant results for ZAP-70 expression and VH status were identified in 12 cases (ZAP-70 positive/VH mutated, 8 cases; ZAP-70 negative/VH unmutated, 4 cases). Of the 8 VH mutated cases with high ZAP-70 expression, only 1 case exhibited unfavorable genomic aberrations, 4 remained in stable disease, 4 developed progressive disease, 3 patients required therapy, and 1 of these 3 died within follow up time. Two of the 3 patients who required therapy, including the patient who died, showed a mutated V3-21 gene rearrangement, associated with an unfavorable outcome. Among the 4 cases with an unmutated VH and low ZAP-70 expression, 2 cases exhibited unfavorable genomic aberrations, 3 cases required therapy, 1 of these 3 died, and for one patient no clinical data were available. In summary, the imbalanced distribution of high risk genomic aberrations was similar when comparing the subgroups according to ZAP-70 expression and VH status. In our series an unmutated VH status predicted for shorter TFS, whereas high ZAP-70 expression did not reach significance. ZAP-70 expression was associated with unmutated VH, but a substantial number of cases showed discordant results for ZAP-70 expression and VH status. The pattern of genomic aberrations and the clinical course of the discordant cases were typical for their respective VH status. Compared to ZAP-70 expression the VH status appeared to be more informative in the prediction of the clinical course in our series of CLL patients.
5
Kumar, Ishan, Shivi Jain Shivi Jain, Ashish Verma, Madhu Jain Madhu Jain, Ram C. Shukla, and Arvind Srivastava. "Discordant Twin Pregnancy with One Malformed Fetus – Color Doppler Follow Up for Expectant Management." Indian Journal of Applied Research 3, no. 9 (October 1, 2011): 469–72. http://dx.doi.org/10.15373/2249555x/sept2013/142.
Full text
6
Phipps, J. B. "Introduction to the red-fruited hawthorns (Crataegus, Rosaceae) of western North America." Canadian Journal of Botany 76, no. 11 (November 1, 1998): 1863–99. http://dx.doi.org/10.1139/b98-148.
Full textAbstract:
Howell's failure in 1898 to typify Crataegus columbiana Howell (the species is based on noncited discordant paratype elements) and the readiness of later authors to make new varieties in this species without resolving the type problem has been the cause of much confusion in the nomenclature of the western red-fruited hawthorns. This has been increased by the failure to recognize Crataegus williamsii Eggl. and compounded by almost a century of no revisionary study on western Crataegus with the further result that boundaries between taxa have been routinely misunderstood outside Colorado. In pursuit of a solution doing least violence to conventional usage I have lectotypified C. columbiana and resuscitated Crataegus piperi Britton (in a recent paper), realigned C. piperi as Crataegus chrysocarpa var. piperi (Britton) Eggl. and resurrected C. williamsii. There are thus five established native western species of red-fruited hawthorns, the above two, and Crataegus wootoniana Eggl., Crataegus macracantha Lodd. ex Loud. and Crataegus erythropoda Ashe in addition to the introduced Crataegus monogyna Jacq., all of which have been recognized as occurring at least somewhere in this region for many decades. This paper also adds the first authenticated record for wild Crataegus laevigata (Poir.) DC. in North America. Separation of the two varieties of C. chrysocarpa is validated by numerical taxonomy. The taxa concerned are illustrated with line drawings and provided with detailed range maps. Colour photographs illustrate typical habitat types and show the development of fruit colour.Key words: systematics, Crataegus, Rosaceae, red-fruited, western North America.
7
Gircys, Michael, and Brian J. Ross. "Image Evolution Using 2D Power Spectra." Complexity 2019 (January 2, 2019): 1–21. http://dx.doi.org/10.1155/2019/7293193.
Full textAbstract:
Procedurally generated images and textures have been widely explored in evolutionary art. One active research direction in the field is the discovery of suitable heuristics for measuring perceived characteristics of evolved images. This is important in order to help influence the nature of evolved images and thereby evolve more meaningful and pleasing art. In this regard, particular challenges exist for quantifying aspects of style and shape. In an attempt to bridge the divide between computer vision and cognitive perception, we propose the use of measures related to image spatial frequencies. Based on existing research that uses power spectral density of spatial frequencies as an effective metric for image classification and retrieval, we posit that Fourier decomposition can be effective for guiding image evolution. We refine fitness measures based on Fourier analysis and spatial frequency and apply them within a genetic programming environment for image synthesis. We implement fitness strategies using 2D Fourier power spectra and phase, with the goal of evolving images that share spectral properties of supplied target images. Adaptations and extensions of the fitness strategies are considered for their utility in art systems. Experiments were conducted using a variety of greyscale and colour target images, spatial fitness criteria, and procedural texture languages. Results were promising, in that some target images were trivially evolved, while others were more challenging to characterize. We also observed that some evolved images which we found discordant and “uncomfortable” show a previously identified spectral phenomenon. Future research should further investigate this result, as it could extend the use of 2D power spectra in fitness evaluations to promote new aesthetic properties.
8
Eyskens, Benedicte, Frank Weidemann, Miroslaw Kowalski, Jan Bogaert, Steven Dymarkowski, Bart Bijnens, Marc Gewillig, George Sutherland, and Luc Mertens. "Regional right and left ventricular function after the Senning operation: an ultrasonic study of strain rate and strain." Cardiology in the Young 14, no. 3 (June 2004): 255–64. http://dx.doi.org/10.1017/s1047951104003038.
Full textAbstract:
Background:Systemic right ventricular dysfunction is a major concern in the follow-up of patients who underwent an atrial redirection procedure for transposition (concordant atrio-ventricular and discordant ventriculo-arterial connections). No good non-invasive method is currently available for quantifying right ventricular function.Aims:We have used ultrasonically based imaging of strain rate and strain to quantify regional deformation in the right ventricle after the Senning operation, comparing properties of regional deformation of the right ventricle with right ventricular ejection fraction as measured using magnetic resonance imaging.Methods:In 20 asymptomatic patients who had undergone the Senning procedure, we measured peak systolic strain rate and systolic strain values in the right ventricular free wall, the septum and the left ventricular lateral wall using colour Doppler myocardial imaging, comparing the data with findings obtained in 30 healthy subjects. Global right ventricular ejection fraction was assessed using magnetic resonance imaging.Results:Properties of deformation of the right ventricular free wall were reduced and homogeneous after the Senning procedure compared to normals, with significantly lower values for peak systolic strain rate and systolic strain (−1.1 ± 0.4 vs. −2.5 ± 0.9 s−1; p < 0.05 and −16 ± 7% vs. −38 ± 13%; p < 0.05, respectively). There was a significant correlation between regional longitudinal right ventricular systolic strain values and right ventricular ejection fraction (r = −0.87, p < 0.001). In the septum, peak systolic strain rate was again reduced and homogeneous (−1.2 ± 0.4 vs. −1.8 ± 0.5 s−1; p < 0.05 vs. normals). Also in the left ventricle, the lateral wall peak systolic strain rate and systolic strain values were reduced (−1.5 ± 0.5 vs. −2.1 ± 0.9 s−1; p < 0.05 and −20 ± 6% vs.−25 ± 9%; p < 0.05, vs. normals, respectively).Conclusions:Properties of regional longitudinal deformation of the systemic right ventricle are reduced after the Senning procedure compared to normal controls, and correlate well with global right ventricular performance. These findings suggest that ultrasonic strain rate and strain imaging could be used in the non-invasive follow-up of ventricular function in these patients.
9
Norrsell, Ulf. "Color Vision and Frithiof Holmgren's Discordant Retinal Microstimulation Findings." Journal of the History of the Neurosciences 19, no. 3 (July 9, 2010): 228–38. http://dx.doi.org/10.1080/09647040902997721.
Full text
10
Elisa de Villemor-Amaral, Anna, Giselle Pianowski, and Lucas de Francisco Carvalho. "Issues About Color, Human Movement, and Number of Responses in the Zulliger Test." Rorschachiana 37, no. 2 (September 2016): 95–113. http://dx.doi.org/10.1027/1192-5604/a000068.
Full textAbstract:
Abstract. This study aimed to verify the scope and limitations of the stimuli of indicators of Color (C), Human movement (M), and Response number (R) of the Zulliger test through a qualitative analysis of the stimuli present in the Zulliger and the Rorschach, comparisons in expressions of C, M, and R, and R relations with evaluative inconsistencies on Zulliger. Taking the Rorschach as a reference, the qualitative analysis indicated a variation from little equivalence up to an overrepresentativeness of Zulliger stimuli. The comparisons, made with a sample of 51 subjects tested with the Zulliger and Rorschach tests and divided into concordant and discordant groups according to the evaluation of instruments, revealed a significant decrease of C and M for the Zulliger. We also identified a tendency toward a decrease of R on Zulliger for the discordant group. The results reveal distinctions between the instruments, limitations of the Zulliger, and instigate investigations for the R-Optimized Administration.
11
Akın, Çiğdem, C. Can Bilgin, and Metin Bilgin. "Discordance between ventral colour and mtDNA haplotype in the water frog Rana (ridibunda) caralitana, 1988 Arıkan." Amphibia-Reptilia 31, no. 1 (2010): 9–20. http://dx.doi.org/10.1163/156853810790457867.
Full textAbstract:
AbstractThe water frog form caralitana was first described as a subspecies of Rana ridibunda by Arıkan (1988) from southwestern Turkey. Its orange ventral colour has been used as a diagnostic character since its description. After testing for a correlation between body size and ventral colour, we compared mtDNA and venter colour of adult specimens from 27 localities to assess the validity of this character for systematics of Anatolian water frogs. We mapped the distribution of each category and tested whether there is concordance between mtDNA haplotype and ventral colour of sampled individuals at the watershed level. Furthermore, we analyzed relationships between ventral colour and altitude. Size and ventral colouration were found to be significantly correlated. The distribution of orange ventral colour exhibited a complex clinal variation especially west of the Lake District where different coloured individuals are seen syntopically. In other regions, there were abrupt changes, presumably because of geographic barriers such as mountains. Our results indicate that although there is significant concordance between caralitana-specific mtDNA and orange venter colour, there are certain watersheds where the majority of sampled individuals exhibits discordance in mtDNA and ventral colouration. In all periphery regions, some degree of genetic introgression is indicated. These patterns clearly indicate gene flow between the caralitana lineage and non-caralitana lineages and is supported by lack of evidence for habitat-specific selection, the assignment of individuals from the same population into distinct clades, and the occurrence of an intermediate character between different forms in transition zones.
12
Martín Moro, Fernando, Miguel Piris-Villaespesa, Monica Garcia Cosio, Jesus Villarrubia, Juan Marquet Palomanes, Ana Lario Arribas, Eulalia Rodríguez Martín, et al. "Diffuse Large B-Cell Lymphoma, Not Otherwise Specified: Discordance between Histology and Flow Cytometry in Bone Marrow Examination at Diagnosis." Blood 132, Supplement 1 (November 29, 2018): 1718. http://dx.doi.org/10.1182/blood-2018-99-117041.
Full textAbstract:
Abstract Background: Bone marrow (BM) examination is essential in the staging of diffuse large B-cell lymphoma (DLBCL). The assessment of BM involvement includes both histology (gold-standard) and flow cytometry (FC), but few studies have compared BM biopsy (BMB) histologic findings with results of FC analysis of BM aspirate. Discordance between both techniques generates debate about the staging and the prognostic significance in these cases. Methods: We performed a retrospective single-center analysis of patients with DLBCL, not otherwise specified (NOS) diagnosed during a 4-year period (2014-2017). Patients were divided in three groups according to BM findings of BMB and FC at diagnosis. Standard FC was performed by 4-color flow panel until 2016 and by 8-color FC since then. We described main characteristics of each group at diagnosis and analyzed survival outcomes. We applied means of descriptive statistics and Pearson's chi-squared test, and analyzed survival outcomes according to Kaplan-Meier, using Cox regression for comparisons. Results: We analyzed 59 cases, which were divided in three groups: 40 cases (67.8%) presented both negative histology and FC (BMB-/FC-), 10 (16.9%) showed BM involvement using both histology and FC (BMB+/FC+) and 9 cases (15.3%) presented discordant results, all of them with negative histology and positive FC (BMB-/FC+). Clinical and biological characteristics of each group at diagnosis are presented in Table 1. Median infiltration by FC analysis of the BMB-/FC+ group was 0.8% (0.1-2.9) and 3/9 patients presented discordant immunophenotype of lymphoma cells between BM and node biopsy. If we considered BM infiltration as positive in all BMB-/FC+ cases, 4/9 (6.8% of all patients) would be upstaged. First-line treatment was homogeneous in all patients. With a median observation time of 18 months, progression-free survival (PFS) after 2 years was 67%, 22% and 22% with BMB-/FC-, BMB-/FC+ and BMB+/FC+, respectively (Figure 1A), with a multivariate hazard ratio (HR) of 1.9 (95% CI 1.2-2.9, p=0.004) and an univariate HR for FC+ (BMB-/FC+ and BMB+/FC+) vs FC- (BMB-/FC-) of 3.3 (95% CI 1.5-7.3, p=0.003). Two-year overall survival (OS) was 68%, 41% and 33% with BMB-/FC-, BMB-/FC+ and BMB+/FC+, respectively (Figure 1B); multivariate HR was 1.6 (95% CI 1.1-2.6, p=0.042) and univariate HR for FC+ vs FC- was 2.5 (95% CI 1.1-5.9, p=0.035). We found no significant difference between BMB-/FC+ and BMB+/FC+ in survival outcomes. Conclusions: In our series, the group with discordant BM infiltration (BMB-/FC+) presented worsen survival outcomes than BMB-/FC-. Such results should be validated in prospective studies because published series are retrospective and not focused specifically on DLBCL. BM infiltration detected by FC analysis but not by BMB could be considered as extranodal involvement at DLBCL NOS diagnosis. Disclosures García Gutiérrez: Novartis: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Incyte: Consultancy, Research Funding, Speakers Bureau.
13
Gladman, Gordon, Frank Casey, and Ian Adatia. "Supravalvar stenosing tricuspid ring in congenitally corrected transposition." Cardiology in the Young 6, no. 2 (April 1996): 174–76. http://dx.doi.org/10.1017/s1047951100003553.
Full textAbstract:
SummaryWe report an unusual case with discordant atrioventricular and ventriculoarterial connections. In addition to the commonly associated intracardiac anomalies ofventricular septal defect and subpulmonary tissue tags, a supravalvar ring was present above the left-sided, morphologically tricuspid valve. This case highlights the value of color flow Doppler echocardiography in making the diagnosis, particularly as the supravalvar ring was seen poorly angiographically.
14
Sonneveld, Edwin, Christian M. Zwaan, Alita J. van der Sluijs-Gelling, Valerie de Haas, Rob Pieters, and Vincent H. J. van der Velden. "Immunophenotyping Versus Morphological Evaluation Of Fresh and Stabilized Cerebrospinal Fluid As Diagnostic Tool For CNS Involvement In Childhood Acute Lymphoblastic Leukemia." Blood 122, no. 21 (November 15, 2013): 4950. http://dx.doi.org/10.1182/blood.v122.21.4950.4950.
Full textAbstract:
Abstract Introduction Presence of malignant cells in cerebrospinal fluid (CSF) is a risk factor in pediatric acute lymphoblastic leukemia (ALL). Consequently, these patients receive extra intrathecal treatment. We evaluated the concordance between morphological and flow-cytometric (FCM) results, both on freshly analyzed and on stabilized, overnight transported samples. Methods Diagnostic CSF samples of 61 newly diagnosed pediatric ALL patients were divided in two aliquots. One was sent to the local laboratory and processed within a few hours after sampling (lab1). A second aliquot was 1:1 diluted with sterile medium and sent to the reference laboratory (lab2). For all samples, a MGG (May-Grünwald-Giemsa) stained cytocentrifuged slide was morphologically evaluated and two 6-color FCM stainings were performed. Samples were considered positive (CNS2) by MGG if at least one blast was seen and by immunophenotyping if a cluster (≥ 10 events) of ALL cells was detected. Results Comparison of morphological data between both laboratories showed concordance in 33 samples (53%). In 20 of the 28 discordant samples only 1 or 2 blasts were reported by a single laboratory. Comparison of FCM data between laboratories was concordant in 58 samples (95%). Three samples (tumor load 15%-18%) were reported positive by one laboratory only; in two of these <100 cells could be acquired per tube. Comparison between FCM and morphology showed discordant results in 25 samples (41%) for lab1 and 19 (31%) in lab2. One discordant case was positive by FCM but negative by morphology, in all others only morphology was reported positive. The latter cases mostly had 1 or 2 blasts reported by morphology, generally not confirmed by the other laboratory. Conclusions This study shows that morphological analysis of CSF samples is non-reproducible if only 1 or 2 blasts are suspected. In contrast, FCM analysis of CSF is highly reproducible between fresh and stabilized samples. Although immunophenotyping still seems less sensitive than morphology, discordant samples generally have only 1 or 2 blasts reported by MGG, which is highly irreproducible. Nevertheless, by using a single 8-color tube higher cell numbers may be acquired and the FCM sensitivity may be increased. Disclosures: No relevant conflicts of interest to declare.
15
den Braber, Anouk, Dennis van ‘t Ent, Danielle C. Cath, Dick J. Veltman, Dorret I. Boomsma, and Eco J. C. de Geus. "Brain Activation During Response Interference in Twins Discordant or Concordant for Obsessive Compulsive Symptoms." Twin Research and Human Genetics 15, no. 3 (June 2012): 372–83. http://dx.doi.org/10.1017/thg.2012.2.
Full textAbstract:
One of the core behavioral features associated with obsessive compulsive symptomatology is the inability to inhibit thoughts and/or behaviors. Neuroimaging studies have indicated abnormalities in frontostriatal and dorsolateral prefrontal – anterior cingulate circuits during inhibitory control in patients with obsessive compulsive disorder compared with controls. In the present study, task performance and brain activation during Stroop color-word and Flanker interference were compared within monozygotic twin pairs discordant for obsessive compulsive symptoms and between groups of pairs scoring very low or very high on obsessive compulsive symptoms, in order to examine the differential impact of non-shared environmental versus genetic risk factors for obsessive compulsive symptomatology on inhibitory control related functional brain activation. Although performance was intact, brain activation during inhibition of distracting information differed between obsessive compulsive symptom high-scoring compared to low-scoring subjects. Regions affected in the discordant group (e.g., temporal and anterior cingulate gyrus) were partly different from those observed to be affected in the concordant groups (e.g., parietal gyrus and thalamus). A robust increase in dorsolateral prefrontal activity during response interference was observed in both the high-scoring twins of the discordant sample and the high-scoring twins of the concordant sample, marking this structure as a possible key region for disturbances in inhibitory control in obsessive compulsive disorder.
16
Mori, Kazuhiro, Masafumi Harada, and Yasuhiro Kuroda. "Twisted atrioventricular valves in double inlet left ventricle." Cardiology in the Young 12, no. 4 (July 2002): 401–3. http://dx.doi.org/10.1017/s1047951100013032.
Full textAbstract:
AbstractTwisted atrioventricular connections usually occur in hearts with biventricular artioventricular connections. Here, we describe a case of twisted atrioventricular valves associated with double inlet left ventricle and discordant ventriculo-arterial connections. Color Doppler echocardiography, and cine magnetic resonance imaging, clearly demonstrated that the right atrioventricular valve was located anterior and superior to the left atrioventricular valve, and that the axes of the two atrioventricular valves crossed each other within the dominant left ventricle.
17
Carnicer, Maria-Jose, Frederik W. van Delft, Lyndal Kearney, and Mel Greaves. "Sub-Clonal Genetic Heterogeneity in BCR-ABL1 Positive Acute Lymphoblastic Leukaemia." Blood 118, no. 21 (November 18, 2011): 1348. http://dx.doi.org/10.1182/blood.v118.21.1348.1348.
Full textAbstract:
Abstract Abstract 1348 Philadelphia-positive (Ph+) acute lymphoblastic leukaemia (ALL), characterised by the BCR-ABL1 fusion gene, occurs in approximately 30% of adult and 5% of childhood ALL and is associated with a poor prognosis. It is considered a single clinical entity with identifiable and recurrent copy number alterations (CNA); notably deletions of the lymphoid transcriptional regulator IKAROS (encoded by IKZF1), PAX5, and CDKN2A/B that are presumed to cooperate with BCR–ABL 1 in lymphoid leukaemogenesis. In particular, IKZF1 deletions are present in 80% of BCR-ABL1 positive ALL cases, and have been implicated as an independent indicator of poor prognosis in childhood ALL. Our previous studies of twin pairs either concordant or discordant for BCR-ABL1+ ALL indicate that the fusion gene is a first hit that occurs prenatally. However, the order and sequence of acquisition of CNA is unknown. We recently reported a complex sub-clonal genetic architecture for leukaemic blasts and leukaemia-propagating (‘stem’) cells in childhood ETV6-RUNX1-positive ALL (Anderson et al., Nature 469: 356–361, 2011). In the present study, we aimed to determine whether similar sub-clonal genetic diversity occurs in BCR-ABL1+ ALL. We carried out five colour FISH to diagnostic blast cells from eight BCR-ABL1 positive cases with differentially-labelled probes for BCR, ABL1, IKZF1, CDKN2A and PAX5. In a subset of cases we also performed Affymetrix single nucleotide polymorphism (SNP 6.0) arrays to determine the specific boundaries of deletions. Four out of the eight cases screened had concurrent IKZF1, PAX5 and CDKN2A deletions. In one case the order of acquisition of these deletions was uninformative, with 97% of cells exhibiting a single FISH pattern (BCR-ABL1+ with monoallelic deletions of all three genes). In the second case, a linear clonal progression was observed with IKZF1 deleted first, PAX5 second and CDKN2A third. In the two remaining cases a branching sub-clonal pattern was observed. In one of these monoallelic IKZF1, CDKN2A and PAX5 deletions all arose independently in different sub-clones; i.e. IKZF1 was deleted first in one subclone, CDKN2A first in another and PAX5 first in a third sub-clone. In the final case we also studied matched diagnosis and relapse samples. Here, SNP array analysis revealed different deletions in all three genes at diagnosis and relapse. Genomic fusion breakpoint analysis revealed an identical BCR-ABL1 genomic sequence at diagnosis and relapse, confirming the same clonal origin of leukaemia. The different deletion boundaries in IKZF1, PAX5 and CDKN2A permitted us to design specific FISH probes to distinguish between ‘diagnostic’ and ‘relapse’ deletions and to track their evolution. The predominant clone at relapse was not a direct evolutionary product of any of the major clones found at diagnosis. The dominant sub-clone at diagnosis was BCR-ABL1+, with a large 9p deletion (encompassing PAX5 and CDKN2A) and a focal CDKN2A deletion, all sub-clonal to a focal IKZF1 deletion. At relapse, the dominant sub-clone had acquired a different IKZF1 deletion, which was sub-clonal to two different (focal, biallelic) deletions of CDKN2A and a different monoallelic PAX5 deletion. The large 9p deletion was not present at relapse. These results indicate the existence of a pre-leukaemic BCR-ABL1 fusion gene positive clone that has given rise to at least two sub-clones, each with different IKZF1, PAX5 and CDKN2A deletions, that have evolved independently. These data indicate that the sub-clonal architecture in this poor prognosis subtype of ALL is genetically diverse, and that key ‘driver’ CNA can arise independently and in no preferential order. Disclosures: No relevant conflicts of interest to declare.
18
Gerber, Amanda, Lisa Koenig, Lori Millner, Lindsay Strotman, Valeria Sero, Nicolò Manaresi, Sabine Kasimir-Bauer, and Farideh Z. Bischoff. "Inter-laboratory evaluation of a novel DEPArray-HER2 FISH assay." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e12506-e12506. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e12506.
Full textAbstract:
e12506 Background: Fluorescent in Situ Hybridization (FISH) is a method currently used for detection and assessment of HER2 gene amplification. Although clinical guidelines set forth by CAP/ASCO exist to ensure accuracy, limitations in HER2test results due to sample preparation, assay-conditions and tumor heterogeneity remain unresolved. We have successfully demonstrated analytical confidence in performing HER2 FISH on DEPArray™ sorted and recovered tumor cells. In this study, we aimed to evaluate inter-laboratory concordance of the DEPArray™ HER2-FISH assay. Methods: Three laboratories equipped with the DEPArray™ were designated as testing sites for this study. Positive control SKBr3 cells embedded in paraffin as well as 20 invasive breast carcinoma FFPE samples were blinded and evaluated by each of the three labs. Control and patient samples were processed through the DEPArray™ beginning with dissociation of the FFPE curls followed by single-cell image-based cell sorting to separate and recover pure distinct tumor cell populations prior to HER2 FISH analysis. Data was only obtained when ∼200 intact cytokeratin+/vimentin-/DAPI+ tumor cells from each sample were recovered and used for subsequent FISH using a standard dual-color HER2/CEP17 FISH procedure. Results: Overall, 80% concordance between DEPArray™-HER2 and conventional HER2 (6 HER2 negative and 10 HER2 positive) was observed between lab(s) and the conventional HER2 method. In each of 4 cases, a discordant HER2 result was reported by one of three sites. In three of these discordant cases, the DEPArray™ HER2 ratio was reported as amplified while the conventional result was negative. In the remaining discordant case, the converse was observed by one site; however, this case was initially evaluated 15 years ago. All three sites correctly scored the SKBr3 positive control cells. Conclusions: The results showed a high concordance rate of correct HER2 status classification. This data further supports the understanding that tissue heterogeneity can indeed give rise to discordant results that may consequently affect treatment options for patients. We demonstrate that sample preparation by DEPArray™ may aid in a more precise classification for tumor biomarker status.
19
Wedger, Marshall J., Tonapha Pusadee, Anupong Wongtamee, and Kenneth M. Olsen. "Discordant Patterns of Introgression Suggest Historical Gene Flow into Thai Weedy Rice from Domesticated and Wild Relatives." Journal of Heredity 110, no. 5 (May 7, 2019): 601–9. http://dx.doi.org/10.1093/jhered/esz030.
Full textAbstract:
Abstract Weedy relatives of crop species infest agricultural fields worldwide, reducing harvests and threatening global food security. These weeds can potentially evolve and adapt through gene flow from both domesticated crop varieties and reproductively compatible wild relatives. We studied populations of weedy rice in Thailand to investigate the role of introgression from cultivated and wild rice in their evolution. We examined 2 complementary sources of genetic data: allelic variation at 3 rice domestication genes (Bh4, controlling hull color; Rc, controlling pericarp color and seed dormancy; and sh4, controlling seed shattering), and 12 previously published SSR markers. Sampling spanned 3 major rice growing regions in Thailand (Lower North, North East, and Central Plain) and included 124 cultivated rice accessions, 166 weedy rice accessions, and 98 wild rice accessions. Weedy rice strains were overall closely related to the cultivated varieties with which they co-occur. Domestication gene data revealed potential adaptive introgression of sh4 shattering alleles from wild rice. Introgression of potentially maladaptive rc crop alleles (conferring reduced dormancy) was also detected, with the frequency of the crop allele highest in northern populations. Although SSR markers also indicated introgression into weed populations from wild and cultivated rice, there was little overlap with domestication genes in the accessions showing admixed ancestry. This suggests that much of the introgression we detected at domestication genes most likely reflects past introgression rather than recent gene flow. This finding has implications for understanding long-term gene flow dynamics between rice and its weedy and wild relatives, including potential risks of transgene escape.
20
Faron, Matthew L., Blake W. Buchan, Christopher Coon, Theo Liebregts, Anita van Bree, Arjan R. Jansz, Genevieve Soucy, John Korver, and Nathan A. Ledeboer. "Automatic Digital Analysis of Chromogenic Media for Vancomycin-Resistant-Enterococcus Screens Using Copan WASPLab." Journal of Clinical Microbiology 54, no. 10 (July 13, 2016): 2464–69. http://dx.doi.org/10.1128/jcm.01040-16.
Full textAbstract:
Vancomycin-resistant enterococci (VRE) are an important cause of health care-acquired infections (HAIs). Studies have shown that active surveillance of high-risk patients for VRE colonization can aid in reducing HAIs; however, these screens generate a significant cost to the laboratory and health care system. Digital imaging capable of differentiating negative and “nonnegative” chromogenic agar can reduce the labor cost of these screens and potentially improve patient care. In this study, we evaluated the performance of the WASPLab Chromogenic Detection Module (CDM) (Copan, Brescia, Italy) software to analyze VRE chromogenic agar and compared the results to technologist plate reading. Specimens collected at 3 laboratories were cultured using the WASPLab CDM and plated to each site's standard-of-care chromogenic media, which included Colorex VRE (BioMed Diagnostics, White City, OR) or Oxoid VRE (Oxoid, Basingstoke, United Kingdom). Digital images were scored using the CDM software after 24 or 40 h of growth, and all manual reading was performed using digital images on a high-definition (HD) monitor. In total, 104,730 specimens were enrolled and automation agreed with manual analysis for 90.1% of all specimens tested, with sensitivity and specificity of 100% and 89.5%, respectively. Automation results were discordant for 10,348 specimens, and all discordant images were reviewed by a laboratory supervisor or director. After a second review, 499 specimens were identified as representing missed positive cultures falsely called negative by the technologist, 1,616 were identified as containing borderline color results (negative result but with no package insert color visible), and 8,234 specimens were identified as containing colorimetric pigmentation due to residual matrix from the specimen or yeast (Candida). Overall, the CDM was accurate at identifying negative VRE plates, which comprised 84% (87,973) of the specimens in this study.
21
Gumusay, Ozge, Mustafa Benekli, Ozgur Ekinci, Meltem Baykara, Ahmet Ozet, Ugur Coskun, Aytug Uner, Ayse Dursun, Ecine Yesim Atak, and Suleyman Buyukberber. "Discordances in HER2 status between primary gastric cancer and corresponding metastatic sites." Journal of Clinical Oncology 33, no. 3_suppl (January 20, 2015): 25. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.25.
Full textAbstract:
25 Background: Determination of HER2 status in advanced gastric cancer (GC) is important in clinical decision making. In the ToGA trial, trastuzumab based therapy demonstrated a significant OS benefit in patients with HER2 positive advanced GC. HER2 discordance in GC primary and its metastases has been long debated. The aim of the study was to evaluate the rate of HER2 discordance and its effect on treatment decisions in advanced GC. Methods: A total of 74 patients with advanced GC were included in the study. Both immunohistochemical staining (IHC) and dual-color silver in situ hybridization (SISH) were performed in all patients to evaluate the HER2 status of the primary lesion and paired metastasis. Results: The assessment of HER2 status with the IHC staining method and SISH revealed a discordance rate of 9.5% and 16.2%, respectively. However, this discordance was clinically meaningful in only one patient leading to a change in treatment decision. While this patient had a HER2 negative status in primary tumor (IHC=0, SISH=negative), the HER2 status was positive for liver metastasis (IHC=2+, SISH=positive). Trastuzumab was added to the chemotherapy regimen. Conclusions: In this study, we found a higher rate of HER2 discordance between primary gastric tumor and metastatic lesions compared to the rates reported in previous studies. Detection of a HER2 positive metastasis with a HER2 negative primary tumor suggests that investigation of HER2 is also required for the metastatic lesion and that trastuzumab could be administered in case of a positive result.
22
Koperski, Paweł, Rafał Milanowski, and Agnieszka Krzyk. "Searching for cryptic species in Erpobdella octoculata (L.) (Hirudinea: Clitellata): discordance between the results of genetic analysis and cross-breeding experiments." Contributions to Zoology 80, no. 1 (February 21, 2011): 85–94. http://dx.doi.org/10.1163/18759866-08001004.
Full textAbstract:
The main aim of this study was to reveal reproduction barriers and potentially cryptic radiation within the very common and morphologically variable leech species - Erpobdella octoculata (L., 1758). The differences in reproductive success of the morphological forms were compared experimentally. The data based on the results of field sampling and analysis of ITS and COI sequences is also presented. The results of the analysis of DNA sequences clearly show lack of reproduction barriers between the analysed morphological forms. Subtle differences in DNA sequences between individuals, found with the use of the arbitrary primers method, seem to be related mainly to geographical distance between sub-populations. On the basis of these results, E. octoculata should be treated as one, valid species, in spite of its great morphological variability. However, experimentally confirmed differences in reproductive success of individuals belonging to morphologically divergent forms may be explained by the presence of reproductive barriers between them. Visible incongruity between the results of DNA sequences and the experimental results is not easy to explain - this question definitely needs further studies. Different percentages of morphological forms noted in field samples, suggests an adaptive value for divergent colour patterns in different habitats. Such differences may be a result of diverse mortality of individuals differing in colour dwelling on different bottom substrate, caused by predation by benthivorous fish.
23
OHMER, MICHEL E., JEANNE M. ROBERTSON, and KELLY R. ZAMUDIO. "Discordance in body size, colour pattern, and advertisement call across genetically distinct populations in a Neotropical anuran (Dendropsophus ebraccatus)." Biological Journal of the Linnean Society 97, no. 2 (May 26, 2009): 298–313. http://dx.doi.org/10.1111/j.1095-8312.2009.01210.x.
Full text
24
Pedicelli, A., C. Distasi, C. Settecasi, G. M. Dilella, C. Colosimo, and M. Rollo. "Studio Eco-Color-Doppler transcranico (ECD TC) degli aneurismi cerebrali." Rivista di Neuroradiologia 13, no. 2 (April 2000): 191–96. http://dx.doi.org/10.1177/197140090001300205.
Full textAbstract:
Verificare le possibilità dell'ECD-TC nella valutazione degli aneurismi cerebrali, a confronto con i dati ottenuti con l'angiografia. Sono stati studiati 12 pazienti con aneurisma cerebrale a distanza di 1–8 giorni da emorragia subaracnoidea. Lo studio è stato condotto in color-doppler, in power-doppler ed in 2 casi anche con mdc ecografico, impiegando sonda transcranica settoriale da 2,5 MHz; la diagnosi era già stata ottenuta con angiografia selettiva. In tutti i pazienti si è ottenuta una soddisfacente visualizzazione dell'aneurisma e dei suoi rapporti con l'arteria parente. I dati dimensionali degli aneurismi sono sempre stati in accordo con quelli angiografici, mentre è stata rilevata discordanza dei dati morfologici in 4 casi. In 6 pazienti è stato possibile visualizzare correttamente l'inflow e l'outflow ed eseguire l'analisi spettrale del flusso intra-aneurismatico. I dati ottenuti, in accordo con quelli della letteratura, fanno ritenere l'ECD-TC metodica altamente specifica ma poco sensibile; la sensibilità aumenta con l'uso del mdc ecografico. Il lavoro fa intravedere prospettive di studio ECD nel controllo dopo terapia chirurgica o endovascolare.
25
Burke, P. H. "Intrapair Facial Differences in Twins." Acta geneticae medicae et gemellologiae: twin research 38, no. 1-2 (April 1989): 37–47. http://dx.doi.org/10.1017/s0001566000002816.
Full textAbstract:
AbstractAnnual serial records in the form of facial contour maps were examined for 18 like-sexed twin pairs of near equal zygosity distribution. Zygosity diagnosis was based primarily on hematological reports for 26 of the 36 children and the remainder were diagnosed on a basis of the concordance or discordance of various physical characteristics: standing height, finger print ridge count, tooth size, and hair and eye colour. Thirteen facial parameters were measured on 274 maps. After age correcting and theree-point smoothing, more than 1,150 intrapair differences of individual facial parameters were measured. In general, the dizygotic twin pairs had the larger mean intrapair differences in facial parameters and the monozygotic twin pairs had the smaller intrapair mean differences. The more important facial parameters for distinguishing the two groups were identified and used to calculate a “facial similarity index”.
26
de Tute, Ruth M., Sharon Barrans, Andy C. Rawstron, Peter W. M. Johnson, Andrew J. Davies, and Andrew Jack. "Patients With DLBCL Commonly Have B-Cell Lymphopenia and Circulating Clonal B-Cell Populations With a Phenotype Concordant With The Underlying Tumour." Blood 122, no. 21 (November 15, 2013): 3013. http://dx.doi.org/10.1182/blood.v122.21.3013.3013.
Full textAbstract:
Abstract Clonal B-cell populations with either a CLL or a non-CLL phenotype are a common finding in normal individuals but uncertainty remains about how this relates to the development of clinically significant disease. The aim of this study was to investigate the frequency of peripheral blood clonal B-cell populations and B-cell subset abnormalities in newly presenting DLBCL patients and to determine whether the incidence of these abnormalities differed between the GCB and ABC subtypes, which are regarded as having distinct pathogenesis. The study was carried out using peripheral blood samples collected from patients entered in the UK-REMoDL-B trial. This trial is testing the hypothesis that the ABC subtype of DLBCL responds preferentially to R-CHOP- Bortezomib. Gene expression profiling is performed on the diagnostic tissue biopsy (FFPE) using the Illumina WG-DASL assay prior to randomisation classified as GCB, ABC or unclassified (UN). The availability of GEP data allows meaningful comparison with the phenotype of clonal populations detected by flow cytometry. Peripheral blood taken prior to first treatment was analysed using multi-colour flow cytometry. Following red cell lysis with ammonium chloride, samples were incubated with a panel of antibodies comprising of a CD19 and CD20 backbone, with Kappa, Lambda, CD5, CD45, CD49d, LAIR-1, CXCR5, CD31, CD95, CD38 and CD10, supplemented in some cases by CD81, CD79b, and CD43. A minimum of 500,000 events were acquired on a FacsCanto II flow cytometer (Becton Dickinson). B-cells were enumerated and any monoclonal populations identified were classified as CLL, germinal centre (GC), non-GC or not otherwise specified (NOS) where the phenotype was indeterminate. 358 samples were eligible for inclusion from patients with an average age of 62.2years (range 22.9-86.1). Abnormalities were detected in 52% of cases (B-lymphopenia ((<0.06 x 109/l) 33%, B-lymphocytosis (>1 x 109/l) 2.8%, CLL clone 3.6%, GC clone 9.8%, non-GC clone 9.8%, clonal population NOS 2.2%). Gene expression profiling results were available for 278 individuals; 51% GCB, 32% ABC and 17% unclassified. The relationship between peripheral blood B-cell findings and the GEP determined phenotype of the tumour is shown in the table:TableB-lymphopeniaCLL CloneMonoclonal GC typeMonoclonalNon-GC typeMonoclonal NOSNormalB-cellGCB n=14241/142 (29%)5/142 (3.5%)21/142 (15%)8/142 (5.6%)2/142 (1%)72/142 (51%)ABC n=8927/89 (30%)2/89 (2%)2/89 (2%)12/89 (13.5%)2/89 (2%)49/89 (55%)Unclassified n=4726/47 (55%)0/50 (0%)2/47 (4%)6/47 (12%)6/47 (5%)14/47 (30%) In patients where clonal populations were detected in the peripheral blood there was striking concordance between the phenotype of the clone and the GEP of the underlying tumour. Presence of a GC-population by flow was highly predictive of GCB GEP (84% GC–type populations detected were in GCB cases). The number of discordant cases and the number of CLL clones detected approximate to the numbers that would be expected in a normal population of a similar age. It is, therefore, likely that in most cases circulating tumour cells or a closely related precursor clone are being detected. The similarity between the results of the ABC and unclassified GEP groups suggest that these are biologically related. An unexpected finding in this study was the high incidence of B-lymphopenia at a level that might be expected to be associated with increased risk of infection. This may reflect suppression of normal B-cells by the neoplastic clone or be a marker of underlying immune dysfunction that may predispose to the development of the tumour. Immuosuppression has a role in the pathogenesis of DLBCL in the elderly and this study suggests that this may also be a factor in the wider patient population. These results may have implications for prognostic assessment and may offer opportunities for early diagnosis and possibly response assessment in some patients. The impact on outcome will be assessed in the course of the trial. Disclosures: Jack: Roche /Genentech: Research Funding.
27
Singh, Sumit Randhir, Alexandre Matet, Elon H. C. van Dijk, Alejandra Daruich, Sascha Fauser, Suzanne Yzer, Enrico Peiretti, et al. "Discrepancy in current central serous chorioretinopathy classification." British Journal of Ophthalmology 103, no. 6 (July 12, 2018): 737–42. http://dx.doi.org/10.1136/bjophthalmol-2018-312435.
Full textAbstract:
AimTo report the discordance in central serous chorioretinopathy (CSCR) classification among practising retina specialists.MethodsThe study conducted was a multicentre survey. Multimodal retinal images along with relevant clinical details of 100 cases diagnosed as CSCR (from six centres) were circulated among six retina specialists across the globe. The image sets included colour fundus photographs, fundus autofluorescence images, optical coherence tomography b-scans, fluorescein and indocyanine green angiography of the study and fellow eyes. The graders were asked to classify the disease of study eye, according to their own criteria. The graders were masked to the responses of other graders. The final analysis of the pooled response data was done based on the diagnosis of study eye only. The main outcome measure was degree of agreement between six independent observers using Fleiss Kappa statistics.ResultsGrading for 100 eyes of 100 patients (men, 93%) was included in the analysis. 20 patients had a history of steroid use. The graders provided 36 different terms to classify the disease, with poor agreement among graders (Fleiss Kappa=0.134). The consistency in diagnosing acute CSCR was statistically higher than for either chronic (p=0.012) or recurrent CSCR (p<0.0001). When collapsing descriptors into six main terms, agreement remained poor (Fleiss Kappa=0.218).ConclusionThe high discordance among experienced retina specialists in describing CSCR clinical subtypes is highlighted. The current work demonstrates the limitations of current empirical CSCR classification methods and the need for a more objective and refined system to bring uniformity in diagnosis and prognostication of the disease.
28
Slack, John F., and Paul R. Coad. "Multiple hydrothermal and metamorphic events in the Kidd Creek volcanogenic massive sulphide deposit, Timmins, Ontario: evidence from tourmalines and chlorites." Canadian Journal of Earth Sciences 26, no. 4 (April 1, 1989): 694–715. http://dx.doi.org/10.1139/e89-059.
Full textAbstract:
Tourmaline and chlorite are the principal ferromagnesian silicate minerals in the Kidd Creek massive sulphide deposit. Tourmaline is most common in sphalerite-rich peripheral margins of the chalcopyrite stringer zone. Within the north orebody, samples typically contain <1% tourmaline, but small areas (hand-specimen scale) may have 10–20%. Chlorite is more widely distributed and in places constitutes 30–50% of rock volumes. Associated assemblages may include quartz, sulphides (principally chalcopyrite, sphalerite, and (or) pyrite), carbonate, albite, sericite, and rare fluorite, allanite, or zoisite(?).The tourmalines and chlorites record a series of multiple hydrothermal and metamorphic events. Paragenetic studies suggest that tourmaline was deposited during several discrete stages of mineralization, as evidenced by brecciation and cross-cutting relationships. Most of the tourmalines have two concentric growth zones defined by different colours (green, brown, blue, yellow). Some tourmalines also display pale discordant rims that cross-cut and embay the inner growth zones and polycrystalline, multiple-extinction domains. Late sulphide veinlets (chalcopyrite, pyrrhotite) transect the inner growth zones and pale discordant rims of many crystals. The concentric growth zones are interpreted as primary features developed by the main ore-forming hydrothermal system, whereas the discordant rims, polycrystalline domains, and cross-cutting sulphide veinlets reflect post-ore metamorphic processes.Detailed electron microprobe analyses of tourmalines show a wide compositional range, from Fe-rich dravite nearly to end-member schorl, with Fe/(Fe + Mg) ratios varying from 0.33 to 0.92; only minor amounts of Ca are present, yielding uniformly high Na/(Na + Ca) ratios of 0.84–0.99. Two sets of chemical zoning trends are identified in the tourmalines, involving systematic changes in Fe/(Fe + Mg), Na/(Na + Ca), Al, and Ti that are believed to reflect internal coupled substitutions (e.g., + Ti = Na + Al) and local mineral equilibria (e.g., tourmaline–chlorite). Analyses of the pale discordant reaction rims show consistent depletion of Fe, Ca, and Ti, presumably by fluid–solid reactions during post-ore metamorphism.Chlorites also show an extensive range in composition, from ripidolite nearly to end-member daphnite, with Fe/(Fe + Mg) ratios of 0.43–0.98 and Si cation values of 5.00–5.39. Chlorites from the fringes of the footwall stringer zone have narrow compositional ranges, whereas chlorites near footwall rhyolite sills in the core of the stringer zone display major variations in Fe/(Fe + Mg) ratios, including one sample with a range of 0.68–0.95. The former group of chlorites has Fe/(Fe + Mg) ratios that correlate well with those of coexisting tourmalines (exclusive of late reaction rims). Data for the latter group, in contrast, fall off equilibrium KD curves, indicating that the tourmalines and chlorites within these samples are not in chemical equilibrium. The chlorites are believed to have been altered (overprinted) by Fe-rich hydrothermal fluids apparently generated during intrusion of the rhyolite sills. The tourmalines, however, are unaffected and retain primary chemical signatures.Variations in mineral proportions and mineral chemistry within the deposit mainly depend on fluctuations in temperature, pH, water/rock ratios, and amounts of entrained seawater. The major proposed control is mixing between high-temperature, Fe-rich end-member hydrothermal fluids and cold, Mg-rich entrained seawater. Fe/(Fe + Mg) variations in footwall tourmalines (and equilibrium chlorites) are believed to largely reflect the progressive infiltration of Mg-rich seawater into the margins and top of the hydrothermal system. The more Fe-rich compositions of Kidd Creek tourmalines relative to those from sediment-hosted massive sulphide deposits (e.g., Sullivan, British Columbia) may be related to the preferential generation of end-member hydrothermal fluids in proximal volcanic environments like that at Kidd Creek.
29
Shichishima, T., T. Terasawa, C. Hashimoto, H. Ohto, M. Takahashi, A. Shibata, and Y. Maruyama. "Discordant and heterogeneous expression of GPI-anchored membrane proteins on leukemic cells in a patient with paroxysmal nocturnal hemoglobinuria." Blood 81, no. 7 (April 1, 1993): 1855–62. http://dx.doi.org/10.1182/blood.v81.7.1855.1855.
Full textAbstract:
Abstract We performed a flow cytometric analysis using monoclonal antibodies to decay accelerating factor (DAF) and CD59/membrane attack complex inhibitory factor (CD59/MACIF) in order to investigate the leukemic cells and erythrocytes from a patient with paroxysmal nocturnal hemoglobinuria (PNH) who developed acute myelocytic leukemia. In May 1990, the leukemic cells comprised 70% of the mononuclear cells in the bone marrow and 76% of those in the peripheral blood. They consisted of a mixture of positive and negative populations, including single DAF- positive cells. In August 1990, almost 100% of the peripheral mononuclear cells were leukemic blasts, and these consisted of a single population with reduced DAF expression. Single-color flow cytometric analysis showed that the leukemic cells lacked CD59/MACIF, while control leukemic cells (n = 3) expressed both DAF and CD59/MACIF. Leukemic blasts from this patient and six control patients expressed lymphocyte function-associated antigen 3 and FcIII receptors (CD 16) both before and after treatment with phosphatidylinositol-specific phospholipase C. The patient's erythrocytes lacking DAF and CD59/MACIF expression corresponded to the proportion of complement-sensitive cells at the onset of acute leukemia. These DAF- and CD59/MACIF-deficient erythrocytes disappeared almost completely with progression of the leukemia. In conclusion, it appears that the expression of glycosylphosphatidylinositol-linked membrane proteins by leukemic cells was heterogeneous and discordant in our patient, and that the leukemic cells were derived from the PNH clone because of their deficiency of CD59/MACIF. It is also suggested that DAF could compete more effectively than CD59/MACIF for a limited number of anchor molecules available on the proliferating leukemic cells.
30
Shichishima, T., T. Terasawa, C. Hashimoto, H. Ohto, M. Takahashi, A. Shibata, and Y. Maruyama. "Discordant and heterogeneous expression of GPI-anchored membrane proteins on leukemic cells in a patient with paroxysmal nocturnal hemoglobinuria." Blood 81, no. 7 (April 1, 1993): 1855–62. http://dx.doi.org/10.1182/blood.v81.7.1855.bloodjournal8171855.
Full textAbstract:
We performed a flow cytometric analysis using monoclonal antibodies to decay accelerating factor (DAF) and CD59/membrane attack complex inhibitory factor (CD59/MACIF) in order to investigate the leukemic cells and erythrocytes from a patient with paroxysmal nocturnal hemoglobinuria (PNH) who developed acute myelocytic leukemia. In May 1990, the leukemic cells comprised 70% of the mononuclear cells in the bone marrow and 76% of those in the peripheral blood. They consisted of a mixture of positive and negative populations, including single DAF- positive cells. In August 1990, almost 100% of the peripheral mononuclear cells were leukemic blasts, and these consisted of a single population with reduced DAF expression. Single-color flow cytometric analysis showed that the leukemic cells lacked CD59/MACIF, while control leukemic cells (n = 3) expressed both DAF and CD59/MACIF. Leukemic blasts from this patient and six control patients expressed lymphocyte function-associated antigen 3 and FcIII receptors (CD 16) both before and after treatment with phosphatidylinositol-specific phospholipase C. The patient's erythrocytes lacking DAF and CD59/MACIF expression corresponded to the proportion of complement-sensitive cells at the onset of acute leukemia. These DAF- and CD59/MACIF-deficient erythrocytes disappeared almost completely with progression of the leukemia. In conclusion, it appears that the expression of glycosylphosphatidylinositol-linked membrane proteins by leukemic cells was heterogeneous and discordant in our patient, and that the leukemic cells were derived from the PNH clone because of their deficiency of CD59/MACIF. It is also suggested that DAF could compete more effectively than CD59/MACIF for a limited number of anchor molecules available on the proliferating leukemic cells.
31
Todorovic, Dejan. "Constancies and illusions in visual perception." Psihologija 35, no. 3-4 (2002): 125–207. http://dx.doi.org/10.2298/psi0203125t.
Full textAbstract:
This paper presents a systematic exposition of the general structure of visual constancies and illusions, including the introduction of a number of conceptual distinctions, illustrated by many examples. The study of these phenomena involves the distal, the proximal, and the phenomenal domain. The relations of concordance and discordance between pairs of domains are defined, followed by the definitions of four visual modes (concordant, proximal, constancy, illusion) as particular constellations of concordance-discordance relations between all three domains. Constancies and illusions are characterized by proximal-phenomenal discordance. Attributes of entities of visual domains are divided into the geometric (size, shape, location, orientation) and the photometric (reflectance, illumination) class. The phenomenal domain involves two types of attributes, one group distally and the other proximally focused. Research on both constancies and illusions can be described as involving the study of the effects of two independent variables on a dependent variable. The first independent variable (target variable) is a distal attribute, such as size, shape etc. In constancy studies, the second independent variable (confound variable), is a variable such as distance, orientation etc, that, together with the confound variable, affects the corresponding proximal variable (such as proximal size, shape etc). In illusion studies, confound variables do not affect the proximal variables, but do affect the corresponding phenomenal variables. The main part of the paper consists in the descriptions of studies of constancies and illusions of size, shape, location, orientation, and achromatic and chromatic color, all presented in a common format, which facilitates the comparison of their similarities and differences. The importance of presentation conditions (full-cue versus reduced cue) and instruction type (distally versus proximally focused) is stressed. Finally, salient cases are pointed out in which relations between phenomenal variables tend to take a form qualitatively similar to the relation of the corresponding non-phenomenal variables.
32
Mullen, Sean P., Nicholas W. VanKuren, Wei Zhang, Sumitha Nallu, Evan B. Kristiansen, Qiqige Wuyun, Kevin Liu, Ryan I. Hill, Adriana D. Briscoe, and Marcus R. Kronforst. "Disentangling Population History and Character Evolution among Hybridizing Lineages." Molecular Biology and Evolution 37, no. 5 (January 13, 2020): 1295–305. http://dx.doi.org/10.1093/molbev/msaa004.
Full textAbstract:
Abstract Understanding the origin and maintenance of adaptive phenotypic novelty is a central goal of evolutionary biology. However, both hybridization and incomplete lineage sorting can lead to genealogical discordance between the regions of the genome underlying adaptive traits and the remainder of the genome, decoupling inferences about character evolution from population history. Here, to disentangle these effects, we investigated the evolutionary origins and maintenance of Batesian mimicry between North American admiral butterflies (Limenitis arthemis) and their chemically defended model (Battus philenor) using a combination of de novo genome sequencing, whole-genome resequencing, and statistical introgression mapping. Our results suggest that balancing selection, arising from geographic variation in the presence or absence of the unpalatable model, has maintained two deeply divergent color patterning haplotypes that have been repeatedly sieved among distinct mimetic and nonmimetic lineages of Limenitis via introgressive hybridization.
33
Ebrashy, Alaa, Mona Aboulghar, Mohamed Elhodiby, Sara H. El-Dessouky, Sherif Elsirgany, Hassan M. Gaafar, Sahar S. Sheta, et al. "Fetal heart examination at the time of 13 weeks scan: a 5 years’ prospective study." Journal of Perinatal Medicine 47, no. 8 (October 25, 2019): 871–78. http://dx.doi.org/10.1515/jpm-2019-0222.
Full textAbstract:
Abstract Objective To evaluate our ability in classifying the fetal heart as normal or abnormal during the 1st trimester scan through fetal cardiac examination and determining the best time for this examination. Methods This was a prospective study performed on 3240 pregnant women to examine the fetal heart. Four chambers view and ventricular outflow tracts were mainly examined during the scan. We used grayscale and color mapping in the diagnosis. Color Doppler was used if additional information was needed, and all patients were rescanned during the 2nd trimester to confirm or negate our diagnosis. Results The cardiac findings were normal at both scans in 3108 pregnancies. The same cardiac abnormality was detected at both scans in 79 cases. In 36 cases there was false-positive diagnosis at the early scan; in 20 of these cases, there were mildly abnormal functional findings early in pregnancy with no abnormality found later. In 17 fetuses, there was discordance between the early and later diagnosis due to missed or incorrect diagnoses. The best time to do fetal heart examination during 1st trimester is between 13 and 13 + 6 weeks. Conclusion A high degree of accuracy in the identification of congenital heart disease (CHD) can be achieved by a 1st trimester fetal echocardiography.
34
Van Winden, Kristi R., Ruben A. Quintero, Eftichia V. Kontopoulos, Lisa M. Korst, Arlyn Llanes, and Ramen H. Chmait. "Pre-Operative Twin Anemia/Polycythemia in the Setting of Twin-Twin Transfusion Syndrome (TTTS)." Fetal Diagnosis and Therapy 37, no. 4 (2015): 274–80. http://dx.doi.org/10.1159/000365919.
Full textAbstract:
Introduction: Twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS) are classified as distinct clinical disorders associated with unbalanced blood flow through placental vascular communications. Typically, TAPS placentas demonstrate few <1 mm arteriovenous (AV) communications, and at fetoscopy the twins are visibly pale and plethoric. Materials and Methods: In a cohort of TTTS patients who underwent laser surgery, those with preoperative findings suggestive of anemia/polycythemia (AP) were compared to those with TTTS alone. AP was defined as middle cerebral artery peak systolic velocity in one twin >1.5 multiples of the median (MoM), and <1.0 MoM in the other. Results: Of 369 TTTS patients, 9 (2.4%) met criteria for preoperative AP. The mean number (±SD) of AV communications in the TTTS + AP group was 5.6 ± 5.7, compared with 8.8 ± 4.8 in the TTTS-alone group (p = 0.013). Five TTTS + AP patients (56%) had a few thin AV communications (mean 2.8 ± 1.6); all 5 had visibly pale and plethoric twins. The remaining 4 (44%) had large or numerous anastomoses (mean 10.5 ± 6.8); none had fetal skin color discordance. Discussion: Preoperative AP affected 2% of TTTS patients. Of these, approximately half had placental and skin color findings typically reported with isolated TAPS.
35
Kumar, Manish, Kishore Kumar, Harinder Pal Singh, Suresh Nair, Amol Patel, Ashok Kumar, and Sneha Soni. "Discordance between Fluorescence In Situ Hybridization and Immunohistochemistry Analysis of Anaplastic Lymphoma Kinase Rearrangement in Indian Patients with Non-Small Cell Lung Cancer." South Asian Journal of Cancer 9, no. 02 (June 2020): 109–14. http://dx.doi.org/10.1055/s-0040-1721191.
Full textAbstract:
Abstract Aims This study aims to evaluate the incidence of anaplastic lymphoma kinase (ALK) mutation in nonsmall cell lung cancer (NSCLC) incorporating fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) methods and to look for any discordance. Methods We evaluated 101 samples obtained from an enriched cohort of NSCLCs patients from the Army Hospital Research and Referral, New Delhi, India, between November 2016 and November 2018. IHC was performed using the highly-sensitive D5F3 rabbit monoclonal primary antibody. FISH was performed with dual-color, break-apart probe (ZytoLight SPEC) on formalin-fixed, and paraffin-embedded tissue. Discordance between IHC and FISH for ALK rearrangements was evaluated. Pearson correlation coefficient (r) was performed to identify any association of ALK presence (by IHC and FISH) with smoking brain metastasis, programmed death-ligand (PD-L1) expression, pleural effusion, and histopathological subtype. Results A total of 7.92% (8/101) cases tested by IHC and 9.9% (10/101) cases tested by FISH were positive for ALK rearrangement. Of 93 ALK IHC-negative cases, 4 were ALK FISH-positive, whereas of 91 ALK FISH-negative cases, 4 were ALK IHC-positive cases. The correlation analysis demonstrated no or very weak correlation in ALK mutations by IHC or FISH with smoking, brain metastasis, PD-L1 expression, pleural effusion, and histopathological examination, except a weak positive correlation (r = 0.33) observed between brain metastasis and ALK rearrangement identified by FISH. Conclusions Our study demonstrated a somewhat similar incidence of ALK FISH-positive cases and ALK IHC-positive cases, though the incidence was numerically higher for ALK-FISH method.
36
Eyding, Jens, Christos Krogias, Marcus Seemann, Ralf Gold, and Achim Mumme. "Review: Discordant findings in color-coded duplex-sonography and magnetic resonance angiography in symptomatic internal carotid artery stenosis: implications for diagnostic work-up and early intervention." Therapeutic Advances in Neurological Disorders 3, no. 1 (December 4, 2009): 69–71. http://dx.doi.org/10.1177/1756285609351763.
Full text
37
Kawakami, Takeshi, Meghan K. Jensen, Andrea Slavney, Petra E. Deane, Ausra Milano, Vandana Raghavan, Brett Ford, Erin T. Chu, Aaron J. Sams, and Adam R. Boyko. "R-locus for roaned coat is associated with a tandem duplication in an intronic region of USH2A in dogs and also contributes to Dalmatian spotting." PLOS ONE 16, no. 3 (March 23, 2021): e0248233. http://dx.doi.org/10.1371/journal.pone.0248233.
Full textAbstract:
Structural variations (SVs) represent a large fraction of all genetic diversity, but how this genetic diversity is translated into phenotypic and organismal diversity is unclear. Explosive diversification of dog coat color and patterns after domestication can provide a unique opportunity to explore this question; however, the major obstacle is to efficiently collect a sufficient number of individuals with known phenotypes and genotypes of hundreds of thousands of markers. Using customer-provided information about coat color and patterns of dogs tested on a commercial canine genotyping platform, we identified a genomic region on chromosome 38 that is strongly associated with a mottled coat pattern (roaning) by genome-wide association study. We identified a putative causal variant in this region, an 11-kb tandem duplication (11,131,835–11,143,237) characterized by sequence read coverage and discordant reads of whole-genome sequence data, microarray probe intensity data, and a duplication-specific PCR assay. The tandem duplication is in an intronic region of usherin gene (USH2A), which was perfectly associated with roaning but absent in non-roaned dogs. We detected strong selection signals in this region characterized by reduced nucleotide diversity (π), increased runs of homozygosity, and extended haplotype homozygosity in Wirehaired Pointing Griffons and Australian Cattle Dogs (typically roaned breeds), as well as elevated genetic difference (FST) between Wirehaired Pointing Griffon (roaned) and Labrador Retriever (non-roaned). Surprisingly, all Dalmatians (N = 262) carried the duplication embedded in identical or similar haplotypes with roaned dogs, indicating this region as a shared target of selection during the breed’s formation. We propose that the Dalmatian’s unique spots were a derived coat pattern by establishing a novel epistatic interaction between roaning “R-locus” on chromosome 38 and an uncharacterized modifier locus. These results highlight the utility of consumer-oriented genotype and phenotype data in the discovery of genomic regions contributing to phenotypic diversity in dogs.
38
Hertzberg, Lawrence, Karina Baggianni, Rosalba Tamayo, Patrick Browne, and Teri Oldaker. "A Comparison of Zap-70 by Immunohistochemistry and Flow Cytometry Using Two Different Flow Analysis Methods." Blood 106, no. 11 (November 16, 2005): 4994. http://dx.doi.org/10.1182/blood.v106.11.4994.4994.
Full textAbstract:
Abstract Zap-70 expression by flow cytometry has been shown to be a surrogate marker for un-mutated/germline IgH status in chronic lymphocytic leukemia (CLL).1 Reproducibility and confidence in the accuracy of results can make this assay problematic. We compared our current single-parameter/one-color, immunohistochemistry (IHC) Zap-70 assay with our flow cytometry Zap-70 assay. Twenty-one (21) patient samples submitted to our lab for Zap-70 testing were assayed by IHC and flow cytometry (FC). In addition, two FC analysis methods were used. One analysis method uses isotype controls to establish negative regions and a 20% cut-off for positivity1, with BD CellQuestTM software (CQ). The other analysis method uses internal negative and positive mean channel fluorescence (MCF) differences using BD Paint-A-GateTM software (PAG). The IHC assay resulted in nine positive, six negative and six equivocal results for Zap-70. The equivocal results were due to very low proportions of CLL cells (three cases) or other problems identified on review of stained slides (three cases). The FC assay resulted in six positive, thirteen negative and two equivocal results for both analysis methods. When comparing IHC Zap-70 and FC Zap-70, there was 29% (6/21) discordance using the CQ analysis and 24% discordance (5/21) using the PAG analysis (equivocal cases included in the denominator only). Comparison of the CQ and PAG analysis demonstrated 16% (3/19) discordance (equivocal cases excluded from the denominator). The FC Zap-70 PAG analysis method correlated somewhat better with the IHC Zap-70 results than did the FC Zap-70 CQ analysis method. This may be due to the variability introduced by user-defined/isotype cursor settings. We conclude that Zap-70 expression can be tested for using either IHC or FC, and that IHC testing may have higher sensitivity. Correlation between the results utilizing these different methods is not ideal, and improvement in both assays, likely including flow analysis methods, is needed. We plan additional, comparative evaluation of more cases. CellQuest™ and Paint-A-Gate™ are trademarks of Becton, Dickinson and Company.
39
Carulli, Giovanni, Sara Galimberti, Giuseppina Bianchi, Alessandra Zucca, Enrico Orciuolo, Gabriele Buda, Giulia Cervetti, and Mario Petrini. "Comparison of Bone Marrow Biopsy, Flow Cytometry and PCR Assays To Detect Bone Marrow Involvement in B-Cell Non-Hodgkin Lymphomas." Blood 106, no. 11 (November 16, 2005): 4670. http://dx.doi.org/10.1182/blood.v106.11.4670.4670.
Full textAbstract:
Abstract Bone marrow biopsy, (BMB) is essential to detect bone marrow (BM) infiltration in B-cell non-Hodgkin lymphomas (NHLs). Flow cytometry (FC) and PCR for clonal IgH rearrangement are considered as ancillary methods, but there is increasing evidence for their clinical usefulness. Observations dealing with combined use of the three methods still are lacking. Thus we carried out a retrospective study about the usefulness of an integrated approach to detect BM infiltration in NHLs. 193 patients suffering from NHLs (79 at presentation, 114 after chemotherapy alone or with: Rituximab, Campath-1, autologous BM transplantation), who had undergone simultaneous execution of BMB, and FC, and PCR from the myeloaspirate on the same iliac crest, were evaluated. BMB was carried out according to standard methods (infiltration pattern and immunohistochemistry). FC was performed using three-color staining, including CD45, to identify: κ/λ ratio, specific phenotype for CLL, MCL and HCL. PCR included identification of IgH rearrangement (CDR3 and VH families), BCL-1/JH translocation for MCL and BCL-2/JH translocation for follicular lymphoma. BMB, FC and PCR agreed in 142 cases and showed infiltration in 74 and lack of infiltration in 68. Cases at presentation were characterized by higher percentages of concordance than cases during the post-chemotherapy (84,8% vs 65.6%). Discrepant results were obtained in 51 cases (26.4%), 13 at presentation and 38 after treatment. In 17 specimens (8.8% of all cases, 33.3% of discordant cases), BM infiltration was detected only by PCR. In 12 of these samples (3 untreated and 14 treated) small B-cell percentages (0.50 ± 0.72, mean ± SD; range 0.02–3.00%) were present at FC. The remaining 5 cases (2.6%) were characterized by a lack of surface Ig expression and absence of specific phenotype: BMB was negative but IgH was clonal. 2 other cases with lack of surface Ig expression (for 7 cases in total, 3.6%), BMB-/PCR- were identified. Conversely, in 10 samples (5.2% of all cases, 19.6% of discordant specimens) PCR failed to detect BM infiltration, which was demonstrated by both FC and BMB. These specimens were characterized by high B-cell percentages (7 ± 8.25, mean ± SD; range 0.3–26.0%) and were obtained from 5 untreated and 5 treated patients. The remaining discordant cases were: 7 treated cases with BMB+/PCR+ and FC-; 6 cases (3 treated and 3 untreated) with FC+ and BMB-/PCR-; 3 treated cases with BMB- and FC+/PCR+; 3 cases (1 untreated and 2 treated) with BMB+ and FC-/PCR-. In the 3 treated cases with lack of amplification by PCR, the following results were observed: FC+/BMB+ in 1 case; FC-/BMB- in the remaining 2. Our data show that no single method is able to identify all cases of BM involvement in NHLs. BMB is actually considered the gold standard, however the combination of the three assays can increase the yields of detection of minimal residual disease. In fact, considering the three assays together as gold standard, BMB alone has a sensibility of 82.1%, a specificity of 96,3%, with 1.6% of false positive but 10.4% of false negative. The PCR can increase the sensibility and FC can than be considered as a valid confirmation assay, able to solve the cases when BMB and PCR show discrepancy. To conclude, the three assays are necessary to evaluate BM infiltration in NHLs, because BMB alone underestimate the BM involvement, especially following treatment.
40
Letestu, Remi, Guillaume Cartron, Stephane Lepretre, Magali Le Garff-Tavernier, Francoise Solly, Lydia Campos, Michel Ticchioni, et al. "Minimal Residual Disease (MRD) By 8-Color Flow Cytometry (Flow-MRD) and IGH Clonospecific Quantitative PCR (ASO RQPCR) Reached Similar Performances for Evaluation of CLL Treatment in a Phase II Clinical Trial: Cross Validation of the Methods." Blood 124, no. 21 (December 6, 2014): 3307. http://dx.doi.org/10.1182/blood.v124.21.3307.3307.
Full textAbstract:
Abstract Evaluation of MRD after treatment has an increasing importance in CLL treatment. Recent studies have demonstrated that patients achieving MRD below 10-4 have significantly longer OS and/or PFS compared to subjects with positive MRD (Böttcher, JCO 2012). Additionally, in CLL patients treated by FC(R)-based regimen, 4-color flow MRD was found as effective as ASO RQ PCR for MRD evaluation down to the level of 10-4, but below that level, PCR was more sensitive (Böttcher, Leukemia 2009). The aim of our study was to investigate the sensitivity of 8-color Flow-MRD and compare it to ASO RQPCR for disease evaluation at post-treatment time-point. 140 patients with active disease were recruited in a randomized first-line phase II trial evaluating the benefit of the addition of a high-dose rituximab pre-phase to standard FCR (R-dense arm) as compared to standard FCR. Clinical response and MRD were monitored at 3 months after last cycle, Flow-MRD was performed in peripheral blood (PB) and bone marrow (BM), and RQPCR in blood only. IGH ASO RQPCR was performed in an EU-MRD laboratory according to EU-MRD guidelines. Results were expressed as 10-8, corresponding to undetectable MRD, when no specific signal was detected, 10-6 when positivity was detected below quantitative range for the patient, and specific number when residual disease was within the quantitative range. For Flow-MRD we have developed an 8-color 9-antibody panel, the analyses were performed in four centers using harmonization procedures. Flow-MRD was considered undetectable (u-MRD) when less than 10 CLL events were detected or if the percentage of CLL events was below the absolute limit of detection (LOD) of the technique established at 0.5x10-6on normal blood samples. Quantitative range was reached when at least 50 CLL events were detected (Rawstron, Leukemia 2012). 137 patients were randomized and analyzed for clinical response. Approximately 87% had MRD evaluation by Flow, ASO RQPCR or both. U-MRD was observed in 81 patients out of 121 tested by flow in blood (67%) and in 49/109 (45%) in marrow. Samples with u-MRD reached good median LOD of 0.7x10-5 and 10-5in PB and BM respectively. MRD results were concordant in PB and BM (undetectable or positive in both samples) in 84/109 patients. The discordant cases were all positive in BM and negative in PB suggesting a better sensitivity and/or informativity in marrow. Therefore, when considering as Flow-MRD positive the cases with positive MRD in PB and/or BM and as undetectable those with u-MRD in BM, Flow-CR rate was 43%. The 66 cases that were analyzed in PB using ASO RQPCR showed a global PCR-CR rate of 76.5%. Sixty patients were analyzed by both flow cytometry and ASO RQPCR in PB. Results were concordant in 49 patients (82%), either both positive (n=9) or undetectable (n=40), resulting in a good global agreement between the two techniques (Kappa coefficient: 0.50 [0.20-0.73]). The 11 cases with discrepant results are of interest as they highlight the importance of the limit of detection for interpretation of MRD results. Among the 7 patients with u-MRD by ASO RQPCR and positive Flow-MRD, 4 showed a median sensitivity of 5.10-5 by ASO RQPCR and a very low median positivity by Flow 0.0024%. Moreover, all these 7 patients had a positive Flow-MRD in BM. The last 4 discordant cases had negative Flow-MRD and positive ASO RQPCR. In 2 of them a poor LOD in Flow-MRD contrasted with a 10-5sensitivity of ASO RQPCR and positive Flow-MRD was found in BM for 2 of these patients. Finally, clinical response was evaluable in 123 patients with MRD results. Among 65 patients in CR or CRi, 16 (24.6%) were MRD positive and among 55 patients in PR or nPR, 29 (52.7%) were MRD negative. Our 8-color panel for MRD detection by flow cytometry in CLL is applicable for treatment evaluation. This work shows that lowering the limit of detection by one log renders the 8 color flow-MRD as sensitive as ASO RQPCR and that the exploration of bone marrow improves the performances of MRD detection. As previously observed using less sensitive techniques, MRD results do not superimpose clinical response. Finally, a longer follow-up will validate the clinical interest of a one-log gain of sensitivity in MRD detection for prediction of PFS and OS. Disclosures Cartron: Roche: Consultancy, Honoraria. Cymbalista:Roche: Honoraria.
41
Hess, Allan D., Christian Meyer, Christopher Thoburn, Ferdynand Kos, Christopher Gocke, Hyam Levitsky, and Judith Karp. "Immune Recovery after Timed Sequential Therapy in Acute Myelogenous Leukemia: Discordant Recovery of Naïve T Lymphocytes and Antigen Driven Regulatory T Cells." Blood 112, no. 11 (November 16, 2008): 947. http://dx.doi.org/10.1182/blood.v112.11.947.947.
Full textAbstract:
Abstract Patients who demonstrate a rapid but limited initial lymphocyte recovery following therapy have a significantly better response rate than patients where lymphocyte recovery is markedly delayed. Timed sequential therapy (TST) is a cell cycle dependent based approach for curative therapeutic potential in acute myelogenous leukemia (AML). Recovery of T cells in this setting can be due to thymic dependent T cell development or as a consequence of directed (antigen) expansion of effector T lymphocytes. The present studies evaluated immunological reconstitution of 26 AML patients following induction or consolidation TST. Thirteen patients received cytarabine, daunorubicin and etoposide (AcDVP-16) induction therapy, 3 patients received cytarabine, daunorubicin and cytarabine (AcDAc) and 10 patients received flavopiridol, cytarabine and mitoxantrone (FLAM) either as induction or consolidation therapy. Peripheral blood lymphocytes were collected during the initial phase of white blood cell reconstitution (>200 cells/ cu mm). Lymphocyte Recovery preceded that of myeloid elements (median of day 24 versus day 30) with peak lymphocyte counts ranging from 300–1800 and a median of 650 cells/cu mm. Multi-color flow cytometric analysis revealed recovery of CD4, CD8 and NK cells with the CD3+CD4+:CD3+CD8+ ratio averaging 4.5:1 (range 1:1– 8:1). Assessment of T cell recombinant excision circles (TREC’s) suggested that a significant proportion of the T cells (median 40,000 copies per 100,000 cells; range 100 – 100,000 copies) were recent thymic emigrants. Somewhat surprisingly, there was a significant expansion of the CD4+CD25+Foxp3+ regulatory T cell compartment (median 5.1%; range 2.5 – 12.3%). To examine whether the expansion of this T cell compartment cells was due to endogenous thymic output or developed by homeostatic mechanisms, CD4+CD25+Foxp3+ cells isolated flow cytometrically were assessed for TREC’s and by spectratyping for Vb T cell receptor gene utilization. The results revealed that the majority (>90%) of CD4+CD25+Foxp3+ cells did not express TREC’s and therefore, did not recently emigrate from the thymus. Moreover, there was a marked oligoclonal skewing as defined by a limited Vb T cell receptor repertoire suggesting expansion did not occur by a non-specific, global homeostatic. In contrast, the repertoire of the non-regulatory T cell compartment (CD4, CD8) was unbiased. These results suggest that the expansion of the CD4+CD25+Foxp3+ T cell compartment is either driven by antigen or by restricted homeostatic mechanisms. The lack of significant, correlative levels of typical homeostatic cytokines (i.e., IL-2, IL-7; Bioplex analysis) may provide an environment where CD4+CD25+Foxp3+ T cells can only be driven to expand by antigenic stimulation. The continued presence of antigen driven regulatory T cells may impede the successful deployment of immunologically directed anti-tumor strategies.
42
Spencer, Andrew, Tiffany Khong, Flora Yuen, Hannah Victoria Giles, Malgorzata Gorniak, Hang Quach, Noemi Horvath, et al. "A Longitudinal Evaluation of Euroflow and Combined Quantitative Immunoprecipitation (QIP) and Free Light Chain (FLC) Mass Spectometry (MS) in Functional High Risk Multiple Myeloma." Blood 134, Supplement_1 (November 13, 2019): 3090. http://dx.doi.org/10.1182/blood-2019-129760.
Full textAbstract:
Introduction: The achievement of minimal residual disease (MRD) negativity is being increasingly recognised as the optimal measure of therapeutic response for both newly diagnosed and relapsed and/or refractory multiple myeloma (MM) patients. Bone marrow (BM) evaluation with either Next Generation Sequencing (NGS) or Next Generation Flow-cytometry (NGF) affords a high level of sensitivity and the attainment of MRD negativity (< 1 in 10-5 MM cells) with either approach is a powerful predictor of superior progression free survival (PFS). Both, however, are limited by the requirement for invasive bone marrow biopsy and the technical limitations imposed by variability in sample quality. Moreover, we and others have demonstrated the presence of significant spatial heterogeneity in MM that increases in the context of disease progression. Against this background we have evaluated a blood-based strategy for disease burden evaluation, Quantitative ImmunoPrecipitation (Mass Spectometry (QIP MS) and Free Light Chain Mass Spectometry (FLC MS) in a uniformly treated cohort of functional high-risk MM patients also undergoing sequential NGF (EuroFlow platform) MRD evaluation. Methods: Newly diagnosed MM patients failing (<partial remission [PR] as best response) front-line bortezomib-based induction therapy were enrolled onto the Australasian Leukaemia and Lymphoma Group (ALLG) MM17 trial (ACTRN12615000934549) evaluating an intensive salvage approach utilising a combination of carfilzomib, thalidomide and dexamethasone (KTd) as re-induction (KTd x 6 cycles) and as post autologous stem cell transplantation (ASCT) consolidation (KTd x 2 cycles followed by Td x10 cycles). NGF MRD status was determined pre-ASCT, post-ASCT and post-KTd consolidation utilising the standardised 8-colour EuroFlow platform. Matched serum samples from the 3 time-points were evaluated in parallel with QIP and FLC MS. Briefly, polyclonal antibodies (anti-IgG, -IgA, -IgM, -total κ, -total λ, free κ and free λ) covalently attached to paramagnetic microparticles were incubated with serum, washed and treated to simultaneously elute and reduce patient immunoglobulins. Light chain mass spectra were generated on a MALDI-TOF-MS system. Concordance between NGF and MS was assessed via the derivation of Cohen's kappa values. Results: Fifty patients were enrolled onto the ALLG MM17 trial. QIP and/or FLC MS identified the serum monoclonal paraprotein (PP) at baseline in all cases (100% sensitivity). Serum samples for MS with matched BM for NGF were available on 33 patients pre-ASCT, 32 post-ASCT and 26 post-KTd consolidation (91 matched samples in total). Sequential MS demonstrated serological complete remission (disappearance of MS baseline detectable monoclonal intact immunoglobulin [PP] and/or FLC) (CRMS) in 11%, 47% and 53% of patients pre-ASCT, post-ASCT and post-KTd, respectively. NGF MRD negativity at the same time points was 39%, 52% and 71% (the latter equivalent to a 50% MRD negativity rate within the original n=50 intention-to-treat population). The Cohen's kappa values for the 3 time-points were 0.21, 0.18 and 0.35 indicating fair to moderate concordance with the best concordance at the post-KTd consolidation time-point and with a Cohen's kappa value for the entire cohort (n=91) of 0.30. The sequential MS demonstrated that 12 patients had discordant disappearance of baseline PP and free light chains (FLC) prior to achieving CRMS. In 11 the FLC disappeared before the PP and in 1 the PP prior to the FLC. The former though to be due to either the FLC falling below the sensitivity of the technique following successful therapy or the presence of 2 sub-clones with differential drug sensitivity, whereas the latter was likely secondary to the persistence of a FLC expressing sub-clone. Post-KTd MS demonstrated good concordance with serological response (Cohen's kappa value = 0.61) but with 18% of patients demonstrating sCR/CR despite persisting MS detectable PP and/or FLC. Conclusion: These preliminary data confirm the utility of QIP MS and FLC MS for the sequential monitoring of tumour burden in HR MM. Concordance with standard monitoring was good with MS detectable disease in some patients with serological sCR/CR consistent with the higher sensitivity of MS. Concordance with NGF was only fair to moderate mandating the future comparison of larger sample sets to better understand the relationship between the 2 methodologies. Disclosures Spencer: Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Secura Bio: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Specialised Therapeutics Australia: Consultancy, Honoraria. Khong:Novartis Oncology: Research Funding. Quach:Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees. Kalff:Amgen: Honoraria; Celgene: Honoraria; pfizer: Honoraria. Reynolds:Novartis Australia: Honoraria; Alfred Health: Employment, Other: Biostatistician for trials funded by the Australian government and Abbvie, Amgen, Celgene, GSK, Janssen-Cilag, Merck, Novartis, Takeda, but sponsored by Alfred Health.; AUSTRALASIAN LEUKAEMIA & LYMPHOMA GROUP (ALLG): Consultancy; Novartis AG: Equity Ownership.
43
Al Harby, Lamis, Mandeep S. Sagoo, Roderick O’Day, Gordon Hay, Amit K. Arora, Pearse A. Keane, Victoria M. L. Cohen, and Bertil Damato. "Distinguishing Choroidal Nevi from Melanomas Using the MOLES Algorithm: Evaluation in an Ocular Nevus Clinic." Ocular Oncology and Pathology 7, no. 4 (2021): 294–302. http://dx.doi.org/10.1159/000511363.
Full textAbstract:
<b><i>Objective:</i></b> The aim of this study was to determine the sensitivity and specificity of the MOLES scoring system in differentiating choroidal melanomas from nevi according to Mushroom shape, Orange pigment, Large tumor size, Enlarging tumor, and Subretinal fluid (SRF). <b><i>Methods:</i></b> Color photographs, fundus-autofluorescence images, and optical coherence tomography of 222 melanocytic choroidal tumors were reviewed. Each MOLES feature was retrospectively scored between 0 and 2 and tumors categorized as “common nevus,” “low-risk nevus,” “high-risk nevus,” and “probable melanoma” according to the total score. MOLES scores were compared with the experts’ diagnosis of melanoma. <b><i>Results:</i></b> The MOLES scoring system indicated melanoma in all 81 tumors diagnosed as such by ocular oncologists (100% sensitivity) and nevus in 135 of 141 tumors given this diagnosis by these experts (95.7% specificity). Of the 6 tumors with discordant diagnoses, 4 had basal diameters exceeding 6 mm, all with SRF and/or orange pigment, and 2 small tumors showed either significant SRF with traces of orange pigment, or vice versa. <b><i>Conclusions:</i></b> The MOLES system for diagnosing melanocytic choroidal tumors compares well with expert diagnosis but needs to be evaluated when deployed by ophthalmologists and community optometrists in a wide variety of working environments.
44
Michallet, Mauricette, Colette Chapuis-Cellier, Christine Lombard, Mohamad Sobh, Thomas Dejoie, Helene Caillon, Michel Attal, Philippe Moreau, and Herve Avet-Loiseau. "Responses Assigned Using Heavy+Light Chain Assessments Have Better Clinical Correlation with Outcome Than Those Using Current IMWG Criteria for Multiple Myeloma." Blood 128, no. 22 (December 2, 2016): 3245. http://dx.doi.org/10.1182/blood.v128.22.3245.3245.
Full textAbstract:
Abstract Introduction: Stratification of multiple myeloma patient responses by reductions in monoclonal component is based upon reliable, historic outcome data. With the introduction of novel agents, a greater number of patients are achieving hitherto unthought-of responses, with many expecting to meet the requirement for VGPR or greater. Multiple factors can impact the quantification and assessment of response in patients achieving deep responses including the influence of IgG recycling, accuracy of quantitation against an increasing polyclonal background and the presence of monoclonal immunotherapies. Alternative strategies for monoclonal protein measurement include heavy+light chain (HLC) immunoassays. Here for the first time we compare the consistency of response assignment between the two methods and evaluate the clinical impact of discordance. Methods: Sera from 509 newly diagnosed intact immunoglobulin multiple myeloma (IIMM) patients enrolled onto IFM-2009 trial were available (median age was 59 (range: 33-66) years, follow-up 30 (3-56) months). Two patients arms were treated with RVDx3+ASCT+RVDx2 or RVDx8, followed by 12 months Lenalidomide maintenance. Responses were assigned at the end of consolidation therapy according to IMWG criteria using changes in monoclonal protein concentrations measured by either SPE or dHLC (clonal - non clonal). Complete response (CR) was assigned by either method by the absence of monoclonal protein on IFE or a normal HLC ratio (HLCr), respectively, and <5% BM plasma cells. HLC-pair suppression was defined as levels of the non-clonal HLC (e.g. IgGλ in an IgGκ patient) below the reference range (IgGκ <3.84g/L; IgGλ <1.91g/L; IgAκ <0.57g/L; IgAλ <0.44g/L). Minimal residual disease (MRD) was assessed by 7-color flow cytometry at the end of consolidation therapy. Results: IFE and HLCr concordantly identified clonality in 99% patients. In 463 patients followed until the end of consolidation we found moderate agreement in response assignment between the two tests. HLC gave similar response assignments to electrophoretic tests in patients with poor response (≤PR, 76/96; 79%) or complete response (≥CR, 130/142; 92%). However in patients achieving VGPR there was considerable discordance between methods for response assignment (102/225; 45%). Having identified discordant results for VGPR we sought to assess the clinical accuracy of the responses assigned within this group. Of the 225 patients with standard VGPR, HLC response assignment varied (PR (18/225), VGPR (102/225) and ≥CR (105/225)). Median PFS for patients achieving standard VGPR was 34.5 months; responses by HLC further described these patients into those with poorer PFS (PR, median PFS=21.3 months (95%CI: 9.0-33.7)); VGPR (PFS=28.9 months (95%CI: 25.1-32.6)), and those with improved outcomes (CR, median PFS not reached); p<0.0001 (Figure 1). This suggested that the response assigned by electrophoresis could be refined by HLC analysis. By contrast, responses assigned by electrophoretic methods offered no added clinical value in patients achieving VGPR (log-rank: p=0.724) or ≥CR (log-rank: p=0.402) by HLC assessment. Furthermore, an abnormal HLCr post-consolidation had a greater concordance with MRD+ assessment (78% positive) compared to IFE (51% positive); whereas both a normal HLCr and negative IFE displayed similar agreement with MRD- assessment (88% and 94% negative, respectively). Finally we assessed the clinical impact of recovering polyclonal immunoglobulin levels after consolidation therapy. In 142 patients with complete responses, HLC-pair suppression (n=15, median PFS=35.1 months (95%CI: 20.9-49.2) and severe suppression (n=7, median PFS=22.9 months (95%CI: 16.6-29.2)) were associated with poorer outcomes (p=0.060 and p=0.004, respectively). Conclusions: In patients achieving a poor or exceptional response there was good agreement between HLC and standard response assignment. For patients achieving a VGPR we suggest that HLC response assignment may be beneficial, therefore overall the assessment could be used to augment or replace electrophoresis. The prognostic significance of HLC responses seems to be partly dependent in the patient's ability to recover their immune system, as determined by normalisation of non-clonal HLC levels. Figure 1 Figure 1. Disclosures Michallet: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Astellas Pharma: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria. Attal:sanofi: Consultancy; janssen: Consultancy, Research Funding; amgen: Consultancy, Research Funding; celgene: Consultancy, Research Funding. Moreau:Novartis: Honoraria; Celgene: Honoraria; Takeda: Honoraria; Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria. Avet-Loiseau:janssen: Consultancy; sanofi: Consultancy; amgen: Consultancy; celgene: Consultancy.
45
Boettcher, Sebastian, Stephan Stilgenbauer, Raymonde Busch, Monika Brüggemann, Thorsten Raff, Kirsten Fischer, Günter Fingerle-Rowson, et al. "Standardized MRD Flow and ASO IGH RQ-PCR for MRD Quantification in CLL Patients after Rituximab-Containing Immunochemotherapy – a Comparative Analysis in 574 Samples from the Randomized GCLLSG CLL8 Trial." Blood 112, no. 11 (November 16, 2008): 3139. http://dx.doi.org/10.1182/blood.v112.11.3139.3139.
Full textAbstract:
Abstract Combinations of purine analogues with the therapeutic anti-CD20 antibody Rituximab induce a high number of complete clinical remissions in CLL patients. Therefore, the detection of minimal residual disease (MRD) appears particularly warranted after such regimens. However, Rituximab prevents the assessment of CD20, one mainstay of flow cytometric MRD detection (MRD flow) in CLL. As no comparative analysis of MRD flow to ASO primer IGH real-time quantitative PCR (RQ-PCR) after Rituximab has been performed so far, doubts remained regarding the diagnostic utility of MRD flow in this clinical setting. We compared results obtained by RQ-PCR to 4-color 3-tube MRD flow in 574 samples from 69 patients randomized to receive fludarabine and cyclophosphamide (FC) or FC plus Rituximab (FCR). Thus we were able to investigate how treatment with FC and FCR impacts on the performance of DNA-based RQ-PCR and of antibody-dependent flow cytometric MRD detection. With 58.4 % positive and 27.0 % negative samples by both assays, we found a qualitative concordance between MRD flow and RQ-PCR of 85.4 % (490/574 samples). Only very few samples were exactly quantifiable with one method and negative by the other method (0.7% MRD flow pos/RQ-PCR neg and 1.4% MRD flow neg/RQ-PCR pos samples). Most discordant samples (12.5% of all samples) were MRD negative by flow but positive by RQ-PCR at low levels outside the quantitative range of MRD detection. We calculated a median quantitative range of 10−4 and a median sensitivity of 2×10−5 in those samples, demonstrating a higher sensitivity of PCR to detect low-level MRD. Considering a threshold of 10−4 for MRD positivity, 94% of all samples showed concordant results by both methods. The cases that were discordantly classified as to this threshold usually comprised samples with residual CLL cells close to 10−4 (3.7% RQ-PCR pos/MRD flow neg and 2.3% RQ-PCR neg/MRD flow pos samples). Quantitative MRD levels determined by both methods were closely correlated irrespective of therapy (Spearman r = 0.95 in FCR, r = 0.96 in FC). We next classified all samples according to the PCR result and compared MRD flow detection rates between the treatment arms. Regarding PCR positive samples within the quantitative range, MRD flow was positive in 96.8% and 98.0% of samples from the FCR and FC arms, respectively. Positive MRD flow results were recorded in 33.7% (FCR) and 40.0% (FC) of samples that concomitantly yielded PCR positive results outside the quantitative range. Within the PCR negative samples, MRD flow detected residual CLL cells in comparable proportions of samples (FCR 2.3% vs. FC 3.4%). We compared the MRD results obtained using combinations that include CD20 (CD20/CD5/CD19/CD43, CD79b/CD20/CD19/CD5) to the MRD results from the combination CD81/CD22/CD19/CD5 in individual samples. We found that CD20 is undetectable on residual CLL cells and therefore not informative for MRD flow in patients from the FCR arm up to 180 days after the last Rituximab infusion. For the same period of time benign B cells are significantly less frequent in patients after FCR than after FC (p<0.0001) and often account for less than 1 cell in 10,000 leukocytes after this therapy regimen. Thus the efficient reduction of background non-CLL B-cells by Rituximab likely explains the high specificity and sensitivity of MRD flow after FCR treatment. In summary, MRD assessment by flow and PCR are equally effective for MRD quantification in Rituximab treated CLL patients within the sensitivity range of 10−4, while PCR is more sensitive for detecting MRD below that level. The use of Rituximab does not influence MRD detection neither by flow nor by RQ-PCR.
46
Humphrey, Kate E., Maria Mirica, Shobha Phansalkar, Al Ozonoff, and Marvin B. Harper. "Clinician Perceptions of Timing and Presentation of Drug-Drug Interaction Alerts." Applied Clinical Informatics 11, no. 03 (May 2020): 487–96. http://dx.doi.org/10.1055/s-0040-1714276.
Full textAbstract:
Abstract Objective Alert presentation of clinical decision support recommendations is a common method for providing information; however, many alerts are overridden suggesting presentation design improvements can be made. This study attempts to assess pediatric prescriber information needs for drug–drug interactions (DDIs) alerts and to evaluate the optimal presentation timing and presentation in the medication ordering process. Methods Six case scenarios presented interactions between medications used in pediatric specialties of general medicine, infectious disease, cardiology, and neurology. Timing varied to include alert interruption at medication selection versus order submission; or was noninterruptive. Interviews were audiotaped, transcribed, and independently analyzed to derive central themes. Results Fourteen trainee and attending clinicians trained in pediatrics, cardiology, and neurology participated. Coders derived 8 central themes from 929 quotes. Discordance exists between medication prescribing frequency and DDI knowledge; providers may commonly prescribe medications for which they do not recognize DDIs. Providers wanted alerts at medication selection rather than at order signature. Alert presentation themes included standardizing text, providing interaction-specific incidence/risk information, DDI rating scales, consolidating alerts, and providing alternative therapies. Providers want alerts to be actionable, for example, allowing medication discontinuation and color visual cues for essential information. Despite alert volume, participants did not “mind being reminded because there is always the chance that at that particular moment (they) do not remember it” and acknowledged the importance of alerts as “essential in terms of patient safety.” Conclusion Clinicians unanimously agreed on the importance of receiving DDI alerts to improve patient safety. The perceived alert value can be improved by incorporating clinician preferences for timing and presentation.
47
Dejoie, Thomas, Michel Attal, Philippe Moreau, and Herve Avet-Loiseau. "Serum Free Light Chain Responses Have Greater Concordance with Clinical Outcomes Than Those Assessed By Urine Electrophoresis in Light Chain Multiple Myeloma Patients." Blood 128, no. 22 (December 2, 2016): 376. http://dx.doi.org/10.1182/blood.v128.22.376.376.
Full textAbstract:
Abstract Introduction Guidelines for monitoring light chain multiple myeloma (LCMM) patients currently rely on measurements of the monoclonal protein in urine (Bence Jones proteinuria). However, the presence of light chains in the urine is highly influenced by the individual free light chain, production rate and renal function, which may make accurate monitoring challenging. Serum free light chain measurements are recommended as diagnostic aid for identifying patients with monoclonal gammopathies and as tools to monitor patients with AL amyloidosis and oligo-secretory MM. The correlation between 24hr urine and serum free light chain (sFLC) measurements is insufficient to consider the tests interchangeable, which has prevented recommendations for replacing urine with serum assessment. Here we compare the performance of serum and urine measurements for monitoring 113 newly diagnosed LCMM patients enrolled onto the IFM-2009 trial; and assess the impact of monitoring by either method with clinical outcome. Methods The IFM-2009 trial randomised patients into either arm A (8xRVD) or arm B (3xRVD followed by high-dose Melphalan with autologous stem cell rescue, and 2 further RVD treatments). All patients received one year of Lenalidomide maintenance therapy. Urine protein electrophoresis (UPEP) and immunofixation electrophoresis (uIFE) were performed prospectively using standard laboratory procedures. sFLC concentrations were measured nephellometrically using κ sFLC and λ sFLC Freelite®assays (The Binding Site Group Ltd, UK). Minimal residual disease (MRD) was assessed by 7-color flow cytometry at the end of consolidation therapy. Results At diagnosis, clonal disease was identified in 100% of patients either by an abnormal κ/λ sFLC ratio or by uIFE. However, whilst all patients had measurable disease by the sFLC assay only 64% had measurable disease using UPEP. The discordance in sensitivity was replicated throughout monitoring and monoclonal light chains were quantifiable after cycle 1 and cycle 3 in 71% vs. 37% patients, and 46% vs. 18%, using sFLC vs. 24hr urine measurements, respectively; in keeping with previous reports. To understand the clinical significance of these discordant findings we compared the depth of response determined by sFLC measurement to those determined by urine electrophoresis after 3 cycles of therapy. Patients with quantifiable disease by sFLC or an abnormal κ/λ sFLC ratio had dismal PFS (median PFS: 36 months vs. not reached, p=0.006; 33 months vs. not reached, p<0.0001, respectively). Whereas quantifiable disease by UPEP was uninformative for PFS (36 vs. 47 months, p=0.260), and abnormal vs. normal uIFE only tended towards significance (36 vs. 47 months, p=0.072); suggesting that monitoring with the sFLC assay is more clinically relevant than with 24hr urine after 3 cycles of therapy. Separating the population into patients with negative UPEP at cycle 3 (n=82), patients with a normal sFLC levels had longer PFS than those with abnormal concentrations (not reached vs. 34 months, p=0.015). Concordant with these results, in 78 patients with negative uIFE, an abnormal κ/λ sFLC ratio still heralded a poorer PFS (34 months vs. not reached, p<0.0001) and importantly overall survival (75% OS: 44 months vs. not reached, p=0.016). In contrast, separating the patients into those with identifiable disease by sFLC or an abnormal κ/λ sFLC ratio, the addition of the urine assessment provided no further discriminatory value. The absence of malignant plasma cells in the bone marrow has been proposed as an important end-point for clinical studies, and therefore we assessed the relationship between early monoclonal light chain removal, as determined by serum and urine assessment, and subsequent elimination of malignant plasma cells. Normalisation of κ/λ sFLC ratio after both 1 and 3 treatment cycles had 100% positive predictive value (PPV) for the prediction of MRD negativity post-consolidation, i.e. all patients whose serum FLC ratio normalised during induction went on to achieve MRD negative status post-consolidation; by contrast patients becoming urine IFE negative at cycles 1 and 3 had PPVs of 81% and 78%, respectively. Conclusions Serum FLC measurements offer improved sensitivity and better correlation with clinical outcome than urine assessments, hence providing a strong basis for recommending the former for monitoring LCMM patients. Disclosures Attal: amgen: Consultancy, Research Funding; celgene: Consultancy, Research Funding; janssen: Consultancy, Research Funding; sanofi: Consultancy. Moreau:Amgen: Honoraria; Celgene: Honoraria; Takeda: Honoraria; Janssen: Honoraria; BMS: Honoraria; Novartis: Honoraria. Avet-Loiseau:amgen: Consultancy; celgene: Consultancy; sanofi: Consultancy; janssen: Consultancy.
48
Tengowski, Mark W. "Image Compression in Morphometry Studies Requiring 21 CFR Part 11 Compliance: Procedure Is Key with TIFFs and Various JPEG Compression Strengths." Toxicologic Pathology 32, no. 2 (February 2004): 258–63. http://dx.doi.org/10.1080/01926230490274399.
Full textAbstract:
This study aims to compare the integrity and reproducibility of measurements created from uncompressed and compressed digital images in order to implement compliance with 21 CFR Part 11 for image analysis studies executed using 21 CFR Part 58 compliant capture systems. Images of a 400-mesh electron microscope grid and H&E stained rat liver tissue were captured on an upright microscope with digital camera using commercially available analysis software. Digital images were stored as either uncompressed TIFFs or in one of five different levels of JPEG compression. The grid images were analyzed with automatic detection of bright objects while the liver images were segmented using color cube-based morphometry techniques, respectively, using commercially-available image analysis software? When comparing the feature-extracted measurements from the TIFF uncompressed to the JPEG compressed images, the data suggest that JPEG compression does not alter the accuracy or reliability to reproduce individual data point measurements in all but the highest compression levels. There is, however, discordance if the initial measure was obtained with a TIFF format and subsequently saved as one of the JPEG levels, suggesting that the use of compression must precede feature extraction. It is a common practice in software packages to work with TIFF uncompressed images. However, this study suggests that the use of JPEG compression as part of the analysis work flow was an acceptable practice for these images and features. Investigators applying image file compression to other organ images will need to validate the utility of image compression in their work flow. A procedure to digitally acquire and JPEG compress images prior to image analysis has the potential to reduce file archiving demands without compromising reproducibility of data.
49
Gattei, V., D. Benedetti, D. Marconi, M. Dal Bo, A. Zucchetto, G. Del Poeta, A. Steffan, R. Bomben, R. Campanini, and M. Degan. "Gene and surface-antigen expression profilings concordantly identify alpha4-integrin/CD49d as a marker for unmutated (UM) bad prognosis B-cell chronic lymphocytic leukemia (B-CLL)." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 10076. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.10076.
Full textAbstract:
10076 Background: The highly heterogeneous clinical courses of B-CLL can be foreseen by investigating IgVH gene mutations or expression of specific prognosticators. Gene and surface-antigen expression profilings (GEP and SEP) have been both employed for identifying molecules of prognostic relevance in B-CLL. Methods: i) GEP - Purified B-CLL cells from 19 UM and 38 mutated (M) cases were investigated for differential GEP by using a two-color Operon Human Genome Oligo Set 2.1 platform with normal B cells as common reference and by applying, after data pre-processing, the LIMMA (Linear Model for MicroArray) package with two combined cutoffs (Bayesian log-odds>1; adjusted p value for false discovery rate <10e−4); ii) SEP - B-CLL cells from 60 UM and 101 M cases were investigated for the expression of 36 surface markers by flow cytometry. Results: i) GEP - 77 probes (32 duplicates) were overexpressed in M B-CLLs (UM/M log-ratio range −0.79/−3.62; p range 6.72e−5/3.6e−10) and 81 probes (46 duplicates) in UM B-CLLs (UM/M log-ratio range 0.87/4.57; p range 9.49e−5/3.01e−12); the CD49d gene was overexpressed in UM cases with UM/M log-ratio of 3.21 (p=8.3e-10). ii) SEP - Six markers significantly discriminated UM to M B-CLLs (t-test, p<10ed-3) and separated most UM (49/60) from M B-CLLs by hierarchical clustering; among them, CD49d was significantly overexpressed in UM cases (median % positive cells 71.2±36 vs. 10.0±31; p=2.1e−10). By applying standardized log-rank statistics in 95 pts, all with CD49d expression and survival data, 30% of positive cells was judged optimal cutoff for identifying two groups with different survivals, 41 CD49dhigh pts showing worse prognosis than 54 CD49dlow cases (p=7.4×10e−5). Similarly, 46 UM B-CLLs had shorter survival than 77 M cases (p=1.4×10e−5). By combining IgVH mutations and CD49d expression, 42 concordant M/CD49dlow pts had better prognosis than 25 concordant UM/CD49dhigh cases (p=1.8×10e−5); noteworthy, among 28 discordant cases, 16 with a M/CD49dhigh phenotype had survival similar to bad prognosis cases. Conclusions: CD49d is a novel prognosticator for B-CLL. Given its high expression level in bad prognosis subsets, CD49d may be a promising therapeutic target. No significant financial relationships to disclose.
50
Eveillard, Marion, Even Rustad, Mikhail Roshal, Yanming Zhang, Amanda Ciardiello, Neha Korde, Malin Hultcrantz, et al. "Using MALDI-TOF mass spectrometry for tracking of minimal residual disease in peripheral blood from patients with multiple myeloma." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e19525-e19525. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e19525.
Full textAbstract:
e19525 Background: Minimal residual disease (MRD) negativity after completed therapy is associated with longer progression-free survival (PFS) in patients with multiple myeloma (MM). Current standard of care for MRD testing use flow cytometry and/or next generation sequencing (NGS)-based assays applied on bone marrow (BM) aspirate samples. To develop a strategy for MRD tracking in peripheral blood (PB), we were motivated to evaluate MALDI-TOF head-to-head with established bone marrow-based MRD assays. Methods: We used MALDI-TOF mass spectrometry to detect M-proteins in PB. Our cohort included patients who had serum samples available at 2 timepoints including during active disease and within 60 days of MRD results as determined by flow cytometry of BM aspirates. The cohort enrolled 71 patients (26 females, 45 males) with a median age of 61 years (37-78 years). Twenty-seven patients had high-risk cytogenetics at baseline. Patients were classified at diagnosis as ISS1 (n = 38), ISS2 (n = 18) or ISS3 (n = 6). The flow cytometry based MRD assay was performed using MSKCCs 10-color, single-tube method. MALDI-TOF analysis was performed as described by Mills et al. Samples taken during active disease were used to identify the mass/charge ratio of the M-protein at baseline and in follow-up samples. MALDI-TOF results were compared to flow cytometry bone marrow-based MRD results. Results: The median time between diagnosis and the MRD timepoint was 13.4 months (3.4-91 months). MALDI-TOF in PB and flow cytometry BM-based MRD results were concordant for 44/71 (62%) patients (8+/+, 36 -/- respectively) while 27 were discordant (10 +/-, 17-/+). Fifty-four of 71 patients were in complete response (CR) (45/54 in sCR) at the time of MRD. MALDI-TOF was still positive in 13 of these 54 CR patients. In this cohort, the median PFS since MRD assessment was not reached in the 2 subgroups of double negative patients (n = 31) or in patients with a positive result in at least one technique (n = 23) with a median follow-up of 11.2 months (0-34.6 months). Conclusions: In 44/71 (62%) samples, MALDI-TOF of PB results and flow cytometry BM-based MRD results were concordant. MALDI-TOF of PB may be useful for detecting measurable residual disease and for the monitoring of MM patients during maintenance therapy with the future goal to rule out early recurrent disease.