The Use of Archives in Endangered Language Preservation: The State of the Art

Conference presentation at the 2015 Annual Meeting of the Linguistic Society of Americ

Variability of Disk Emission in Pre-Main Sequence and Related Stars. I. HD 31648 and HD 163296 - Isolated Herbig Ae Stars Driving Herbig-Haro Flows

Infrared photometry and spectroscopy covering a time span of a quarter century are presented for HD 31648 (MWC 480) and HD 163296 (MWC 275). Both are isolated Herbig Ae stars that exhibit signs of active accretion, including driving bipolar flows with embedded Herbig-Haro (HH) objects. HD 163296 was found to be relatively quiescent photometrically in its inner disk region, with the exception of a major increase in emitted flux in a broad wavelength region centered near 3 microns in 2002. In contrast, HD 31648 has exhibited sporadic changes in the entire 3-13 micron region throughout this span of time. In both stars the changes in the 1-5 micron flux indicate structural changes in the region of the disk near the dust sublimation zone, possibly causing its distance from the star to vary with time. Repeated thermal cycling through this region will result in the preferential survival of large grains, and an increase in the degree of crystallinity. The variability observed in these objects has important consequences for the interpretation of other types of observations. For example, source variability will compromise models based on interferometry measurements unless the interferometry observations are accompanied by nearly-simultaneous photometric data.Comment: 55 pages, 18 figures, 2 tables, Accepted by Ap

Do U.S. Tax Court Judge Attributes Affect Corporate Tax Dispute Outcomes?

Corporate taxpayers can have economically meaningful disputes with the IRS that ultimately involve the federal judiciary. In an attempt to reduce the number of corporate tax disputes going to trial and reduce the amount of time between when corporate taxpayers file a petition with the U.S. Tax Court and resolution of the case, politicians and judges have placed greater emphasis on negotiated settlements as opposed to Tax Court trials. In this paper, we investigate whether the personal attributes of the Tax Court judge assigned to the case (political ideology, professional experience, and tenure on the bench) influence corporate taxpayers and the IRS to reach a negotiated settlement or to proceed to trial. Overall, our results show that Tax Court judges who are conservative, have private practice experience, have governmental legislative experience, and have longer tenure on the Tax Court bench are more likely to preside over disputes resolved through a negotiated settlement as opposed to going to a trial

A comparison of time delay and decreasing prompt hierarchy strategies in teaching banking skills to students with moderate handicaps.

Four students with moderate handicaps were taught to cash checks and to use an automatic teller through either a decreasing prompt hierarchy or time delay procedure. The strategies were compared within a multielement design. Results indicated that both strategies led to the acquisition of the target tasks; however, the decreasing prompt hierarchy was more efficient. Four and 8-week follow-up probes indicated that the strategies were equally effective in producing maintenance of performance

Diagnosis to Treatment Interval (DTI) Informs Outcomes across Subtypes of Aggressive B-Cell Lymphoma

Background: Shorter diagnosis to treatment interval (DTI) has been shown to be associated with more aggressive disease features and inferior outcomes in diffuse large B-cell lymphoma (DLBCL; Maurer et al, JCO 2018). Additional confirmatory studies have also shown that DTI is related to tumor volume (Alig et al, JCO 2021) and molecular phenotype (Aluaij et al, Blood 2023). Here we evaluate DTI in a large multicenter cohort of patients prospectively enrolled and followed as part of the Lymphoma Epidemiology of Outcome (LEO) cohort. Methods: Patients were enrolled within 6 months of diagnosis at one the 8 LEO cohort academic medical centers in the United States between 2015 and 2020. Patients in this analysis had aggressive B-cell lymphoma (BCL) treated with anthracycline-based chemotherapy. DTI was defined as the initial lymphoma biopsy date until the start of initial chemotherapy; patients with DTI between 0-100 days were evaluated. Short DTI was defined as DTI ≤ 14 days (DTI≤14) as previously described in prior publications (e.g. Maurer et al, JCO 2018) and confirmed via examination of functional forms via splines. Event-free survival (EFS) was defined as the time from start of treatment until progression/relapse, retreatment, or death due to any cause. Overall survival (OS) was defined as the time from start of treatment until death due to any cause. Results: 2565 patients with aggressive B-cell lymphoma were evaluated. Median age was 62 years (IQR 51-71) and 1469 (57%) were male. 297 patients (12%) were self-reported non-White race and 314 patients (12%) were self-reported Hispanic or Latino. The majority had DLBCL, NOS subtype (N=1927, 75%), while 227 (9%) had high-grade BCL with MYC and BCL2 and/or BCL6 rearrangements (HG, DH) and 90 (4%) had high-grade BCL NOS (HG, NOS). Clinical characteristics are summarized in the table. At median follow-up of 49 months (IQR 36-68), 800 patients (31%) had an event and 578 patients (23%) died. EFS at 24 months (EFS24) was 76% (95% CI: 74-77). Median DTI across all subtypes was 21 days (IQR 12-33) and 845 patients (33%) had DTI≤14. Patients with DTI≤14 were significantly younger (median age 59 years) but there was no association between DTI and gender, race, or ethnicity. Patients with DTI≤14 were more likely to have HG, DH or HG NOS subtypes, ECOG PS 2-4, advanced stage, elevated LDH, CNS involvement, B symptoms, and bulky disease ( see table). Patients with DTI≤14 were more likely to receive R-EPOCH-based or intensive therapies (41%) and less likely to receive 1L therapy on a clinical trial (3.8%) compared to DTI>14 (26% and 10.1%, respectively). Consistent with previously reported data, DTI≤14 was associated with inferior EFS (HR=1.62, 95% CI: 1.41-1.87, figure), OS (HR=1.73, 95% CI: 1.47-2.04), and EFS24 (OR=1.93, 95% CI: 1.60-2.38). The association between DTI and outcomes remained significant after stratifying for subtype (EFS HR=1.68, 95% CI: 1.46-1.94; OS HR=1.78, 95% CI: 1.50-2.10) and adjustment for IPI (EFS HR=1.43, 95% CI: 1.24-1.65; OS HR=1.47, 95% CI: 1.24-1.74). In subset analysis, DTI≤14 was significantly associated with inferior outcomes within the subtypes of HG, DH (EFS HR=2.70, 95% CI: 1.82-4.01; OS HR=2.97, 95% CI: 1.92-4.60); HG, NOS (EFS HR=2.07, 95% CI: 0.93-4.60; OS HR=2.36, 95% CI: 1.03-5.43); and DLBCL, NOS (EFS HR=1.51, 95% CI: 1.27-1.78; OS HR=1.52, 95% CI: 1.45-1.85). Analysis was limited in other subtypes due to number of events. Notably, within the subset of patients with DTI>14, there was no significant difference in EFS between subtypes for DLBCL, NOS (EFS24=80%, EFS HR=ref), HG, DH (EFS24=73%, EFS HR=1.26, 95% CI: 0.92-1.73) and HG, NOS (EFS24=83%, EFS HR =0.84, 95% CI: 0.40-1.78), logrank p=0.29; similar results were observed for OS (p=0.22). Conclusions: Patients requiring early initiation of therapy for aggressive B-cell lymphoma represent a distinct population of patients with more aggressive clinical features and inferior outcomes. In patients with longer DTI, high grade subtypes had similar outcomes to DLBCL, NOS. Efforts should be made to include patients with anticipated short DTI in clinical trials and translational studies to fully capture the spectrum of patients with aggressive B-cell lymphoma

Comparing Clinical Characteristics and Outcomes of MYC and BCL6 Double Hit Lymphoma (DHL- BCL6 ) with Other Aggressive B-Cell Lymphomas: Understanding the Impact of New Who and International Consensus Classifications

Background: High Grade B cell Lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements(R) was introduced as an entity in 2016 by the WHO revised 4 th edition. In 2022, both the WHO 5 th edition (beta version) and the International Consensus Classification (ICC) separated DHL- BCL2 (+/- BCL6-R)from DHL- BCL6 given differences in biology . However, while the ICC has maintainedDHL- BCL6 as a provisional entity, the WHO has removed the category, thus removing the requirement to FISH for BCL6-R in this setting. Clinical data on DHL- BCL6 is much more limited, as these cases represent only 10-20% of DHL and have been combined with BCL2-R cases in prior studies. Outcomes are variable in retrospective studies with no consistent data on prognosis or optimal therapeutic strategies. By retaining the category of DHL-BCL6 as a provisional entity, the ICC emphasized the need for further, multicenter, prospective studies evaluating the clinical and biological features of this disease. We herein report a comprehensive comparison of clinical characteristics and outcomes in patients with DHL- BCL6 compared to diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS); DLBCL with MYC rearrangement only; DHL- BCL2; and HGBL, NOS in a large, multicenter, prospective cohort of patients from Lymphoma Epidemiology of Outcomes (LEO). Methods: Adult patients with newly diagnosed large B-cell or HGBL were enrolled within 6 months of diagnosis at one the 8 LEO cohort academic medical centers in the US between 2015 and 2020. Baseline characteristics were abstracted at the time of diagnosis per protocol. Based on FISH data patients were further sub mgrouped into DLBCL, NOS (without MYC rearrangement); MYC-R DLBCL, NOS; HGBL, NOS; DHL- BCL2 and DHL- BCL6. Event-free survival (EFS) was defined as the time from diagnosis until progression/relapse, retreatment, or death. Overall survival (OS) was defined as the time from diagnosis until death due to any cause. Results: A total of 1526 eligible patients were identified during this time period. All FISH data was available at the time of diagnosis and the choice of treatment was based on physician discretion. Median age at diagnosis was 63 years (IQR 53-72), with 148 (10%) patients in the AYA category, and 128 (8%) patients > 80 years. 58% (891) were male, 11% self identified as Hispanic or Latino, and 7% as Black/African American. The median diagnosis to treatment interval (DTI) was 20 days (IQR 12-32), and 33% had DTI < 14 days. The FISH-based subgroups were MYC-negative DLBCL, NOS (N=1146, 75%), MYC-R DLBCL,NOS 227 (N = 96, 6%), DHL- BCL2 (N=154, 10%), DHL- BCL6 (N=38, 3%), and HGBL, NOS (N=92, 6%). When available, COO by Hans algorithm was 92% GCB in DHL- BCL2 and 50% GCB in DHL- BCL6. Clinical characteristics can be found in the table. At a median follow-up of 49 months (IQR 36-67), 490 patients (32%) had an event and 356 patients (23%) died. EFS at 24 months (EFS24) was 75% (95% CI: 73-77). Patients with DHL- BCL6 were younger at diagnosis (median 60 years), had more extranodal site involvement (40%), more often stage III/IV disease (70%), and more often treated with a higher intensity regimen than R-CHOP (69%) compared to DLBCL,NOS and MYC-R DLBCL. DHL- BCL6 also had fewer patients that were males (47%), with DTI <=14 days (33%), NCCN IPI ≥ 4 (45%), elevated LDH (53%) than HGBL, NOS and DHL- BCL2. The 2-year EFS and OS rates were noted to be significantly better in the DHL- BCL6 (EFS 79%, 95% CI: 67-93; OS 92%, 95% CI: 84-100) as compared to DHL- BCL2 (EFS 58%, 95% CI: 50-66; OS 70%, 95% CI 63 - 78) and HGBL, NOS (EFS 74%, 95% CI: 65-84; OS 74%, 95% CI: 65-84 ), (Figure 1) but were comparable to that of DLBCL, NOS (EFS 78%, 95% CI: 76-81; OS 87%, 95% CI: 86-89). Conclusions: Our data support separating DHL- BCL6 from DHL -BCL2 as these patients form a unique subgroup with some clinical characteristics comparable to both DLBCL, NOS as well as HGBL, NOS and DHL- BCL2 subtypes. In this cohort, clinical outcomes are more comparable to DLBCL, NOS than DHL- BCL2 or HGBCL, NOS. More frequent use of intensive chemotherapy in DHL- BCL6 compared with DLBCL may account for this finding, although larger multicenter studies are needed. Our results support continued identification of DHL- BCL6 in the clinical setting to better understand optimal therapy and biology of this cohort

Utility and Patterns of Use of PET/CT and Bone Marrow Biopsy for Staging in Non-Hodgkin Lymphoma in the Clinical Setting: A Retrospective Analysis Using the LEO Database

INTRODUCTION Complete staging via bone marrow assessment is standard of practice for most newly diagnosed non-Hodgkin lymphoma (NHL) patients, though the methods and patterns of bone marrow assessment vary in clinical practice. The 2014 Lugano Classification recommends that in diffuse large B cell lymphoma (DLBCL), positron emission tomography-computed tomography (PET/CT) alone can designated advanced-stage disease in many, but not all cases. For most other NHL subtypes, obtaining bone marrow biopsy (BMB) remains recommended. We aimed to assess clinical practice patterns of marrow assessment and the performance of PET/CT in the clinical setting. METHODS The Lymphoma Epidemiology of Outcomes (LEO) cohort is a prospective cohort from 8 academic medical centers. All patients were enrolled in the cohort within 6 months of diagnosis, and prospectively followed. Patients with lymphoma enrolled in the cohort between July 2015 and June 2017 were included for study. Baseline clinical characteristics at diagnosis, whether BMB and/or PET/CT were performed, and the result of these assessments were extracted from the database. Bone marrow involvement on PET/CT was abstracted via review of radiology reports. No central review of images was utilized. RESULTS In total, 3,251 patients were included, consisting of the following subtypes: DLBCL (n=1,098), follicular lymphoma (FL n=730), mantle cell lymphoma (MCL n=302), T-cell lymphoma (TCL n=278), marginal zone lymphoma (MZL n=269), other NHL (n=505) and composite lymphoma (n=69). Other clinical characteristics are shown in table 1. Staging BMB was obtained in 78% of patients, PET/CT was obtained in 56%, both BMB and PET/CT were obtained in 46% while neither were obtained in 9% (table 1). There were significant differences in lymphoma subtype between patients having any bone marrow assessment vs no bone marrow assessment (p<0.0001). MCL (96%) and DLBCL (94%) most frequently had any bone marrow assessment, while MZL was least frequently assessed (84%). Patients undergoing any bone marrow assessment had higher median lactate dehydrogenase (247 U/L vs 206 U/L, p=0.0002). Among the 8 enrolling medical centers, the frequency of bone marrow biopsy at diagnosis ranged from 53% to 86%, and the frequency of PET/CT at diagnosis ranged from 34% to 94% (p<0.0001, table 1). Among patients with DLBCL who had positive bone marrow by either PET/CT or BMB (N=107), 41% (44/107) were positive by BMB only, 19% (20/107) were positive by PET/CT only, and 40% (43/107) were positive by both. Figure 1 shows results of similar analyses for FL, MCL, MZL, and TCL. Using BMB as a gold standard for marrow involvement, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PET/CT for marrow assessment in DLBCL is 49%, 90%, 68% and 91%, respectively. Data for other subtypes are shown in table 2. Patients undergoing both PET/CT and BMB had lower median LDH (231 U/L vs 254 U/L, p=0.0032) than those undergoing one or neither assessments. CONCLUSION Overall, 91% of all patients with newly diagnosed NHL had bone marrow assessments via either PET/CT, BMB or both. The significant variation in the frequency of BMB and PET/CT use among the 8 centers reflects a lack of clear consensus on staging practices regarding bone marrow assessment. The sensitivity of PET/CT for detection of marrow involvement was less than 50% across all subtypes. It is possible the sensitivity of PET/CT could be improved via a centralized review process of the images, as is performed in some clinical trials, however practical approaches for implementing such reviews in clinical practice have not been developed. Between 92-100% of all positive bone marrows were detected by BMB, except in cases with DLBCL in which 19% of positive bone marrows were missed by BMB but detected by PET/CT. Thus, in our analysis, BMB more reliably captured marrow involvement that PET/CT in all subtypes in which both assessments were performed. However, neither PET/CT nor BMB alone were able to identify all cases of bone marrow involvement and use of both modalities may be necessary in cases where marrow involvement would have clinically important implications. Disclosures Rutherford: Juno Therapeutics Inc: Consultancy, Honoraria; Janssen Scientific Affairs: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Heron: Consultancy, Honoraria. Kahl:ADC Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy; TG Therapeutics: Consultancy; BeiGene: Consultancy. Lossos:Janssen Scientific: Membership on an entity's Board of Directors or advisory committees; NIH: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Friedberg:Acerta: Other: Data & Safety Monitoring Committee; Bayer: Honoraria, Other: Data & Safety Monitoring Committee. Casulo:Celgene: Research Funding; Roche: Other: Travel, accommodation, expenses; Gilead: Honoraria, Other: Travel, accommodation, expenses. Cohen:Astra Zeneca: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Hutchison: Research Funding; Gilead/Kite: Consultancy; Bristol-Meyers Squibb Company: Research Funding; LAM Therapeutics: Research Funding; UNUM: Research Funding; Lymphoma Research Foundation: Research Funding; ASH: Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy; Genentech, Inc.: Consultancy, Research Funding. Nastoupil:TG Therapeutics: Honoraria, Research Funding; Novartis: Honoraria; Spectrum: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding; Gilead: Honoraria; Bayer: Honoraria. Flowers:Denovo Biopharma: Consultancy; Spectrum: Consultancy; National Cancer Institute: Research Funding; Optimum Rx: Consultancy; Burroughs Wellcome Fund: Research Funding; Acerta: Research Funding; Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Eastern Cooperative Oncology Group: Research Funding; TG Therapeutics: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Karyopharm: Consultancy; AstraZeneca: Consultancy; Pharmacyclics/Janssen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; V Foundation: Research Funding; Millenium/Takeda: Research Funding; Celgene: Consultancy, Research Funding. Cerhan:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; NanoString: Research Funding. Martin:Sandoz: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; Teneobio: Consultancy; I-MAB: Consultancy; Janssen: Consultancy

Real-World Impact of Differences in the World Health Organization (WHO) Classification and International Consensus Classification (ICC) Systems on the Diagnosis of Non-Hodgkin Lymphoma: An Analysis from the LEO Cohort Study

Introduction: The use of standardized, evidence-based classification systems is crucial for the accurate diagnosis and treatment of diseases. Moreover, standardized classification facilitates research and epidemiologic studies and promotes consistency in communication among healthcare professionals. Since 2016, the revised 4 th edition of the World Health Organization classification (WHO-HAEM4R) has been the global standard for diagnosis of lymphoid malignancies. With the emergence of new data, 2 new classification systems were developed and published in 2022: the 5 th edition of the WHO Classification (WHO-HAEM5) and the International Consensus Classification (ICC). Both WHO-HAEM5 and ICC maintain a shared fundamental concept of disease classification that integrates clinical, pathologic, and molecular data. However, they differ on nomenclature, establishment of new entities, and/or diagnostic criteria for some disease categories. To evaluate the impact of these differences on real-world diagnosis of non-Hodgkin lymphoma (NHL), we examined the diagnostic classification of NHL in the Lymphoma Epidemiology of Outcomes (LEO) Cohort Study (NCT02736357). Methods: Initiated in 2015, LEO is an ongoing prospective observational study of patients aged ≥18 years with newly diagnosed NHL. Patients are enrolled at 8 major U.S. medical centers. Clinical, epidemiologic, pathologic, and treatment data are abstracted at baseline and active follow-up is conducted for all patients. Lymphoma subtype is coded for each case based on expert hematopathology re-review of the diagnostic pathology slides, the pathology report, biomarker data, and clinical data. Of note, NHL subtype distribution is similar to SEER data. We studied all patients enrolled in LEO between 7/1/2016 (the date LEO pathology review started using WHO-HAEM4R diagnostic codes) and 5/31/2020. WHO-HAEM4R diagnoses and additional clinicopathologic data, when relevant, were used to map cases into the corresponding WHO-HAEM5 and ICC diagnoses. Differences between WHO-HAEM5 and ICC were annotated for each case as: None - same disease entity; Minor - difference in nomenclature with similar diagnostic criteria; Major - difference in disease category and/or diagnostic criteria; or Unevaluable - insufficient data to assign WHO-HAEM5 and/or ICC diagnosis. Results: LEO enrolled 6143 patients during the study period. Of these, comparison between WHO-HAEM5 and ICC was evaluable in 5730 (93.3%). Unevaluable cases included those without a specific WHO-HAEM4R diagnosis at enrollment (N=384; e.g., patients with a low-grade B-cell lymphoma that could not be definitively sub-classified) and those with a specific WHO-HAEM4R diagnosis, but with insufficient clinicopathologic data to assign a specific WHO-HAEM5 and/or ICC diagnosis (N=29). Of the 5730 evaluable cases, 5376 (93.8%) showed no difference between WHO-HAEM5 and/or ICC diagnosis, 311 (5.4%) showed minor differences (nomenclature only), and 43 (0.8%) showed major differences (Table 1). The 43 major differences all involved B-cell NHLs; 20 (46.5%) were attributable to different approaches to classifying double-hit lymphomas, 21 (48.9%) to classification of splenic/leukemic B-cell lymphomas, and 2 (4.6%) to classification of B-cell lymphomas occurring at specific anatomic sites (Table 2). Conclusion: In a large, prospective lymphoma cohort reflecting real-world clinical practice at 8 major U.S. medical centers, major diagnostic differences in the classification of NHL using WHO-HAEM5 or ICC classification criteria were seen in 0.8%, whereas the remaining 99.2% of diagnoses were either the same or showed differences in nomenclature only. The existence of 2 concurrent classification systems presents potential for discrepancies in pathologic diagnosis, clinical practice, clinical trials, and other lymphoma research. Furthermore, some of the differences between WHO-HAEM5 and ICC are clinically and potentially therapeutically significant, and their resolution requires further study. Nevertheless, our findings argue that the proportion of patients affected would be small in real-world practice settings. This appears largely related to incidence rates of specific lymphoma subtypes, with major differences between the 2 classifications predominantly affecting rare entities, while there is general concordance on the most common forms of NHL