ALBERT

Description: The origin and age of topography along the west Greenland margin is a matter of continued debate. Evidence for tectonically driven Neogene uplift has been argued from interpretations of offshore seismic surveys, onshore fission-track data and inferred episodes of cooling. Here, analysis of seismic reflection profiles and 1D modelling of exploration wells along the Greenland margin of Davis Strait demonstrate that the data are consistent with a model of ancient continental topography affected by late Cretaceous–early Palaeocene rifting followed by thermal subsidence where offshore Neogene tectonic uplift is not required. This interpretation for the offshore evolution of the west Greenland margin has implications for the adjacent onshore evolution and for other continental margins developed throughout the Atlantic–Arctic rift system.

Description: Neoproterozoic basaltic magmatism in the Dalradian Supergroup of Scotland and Ireland was associated with the break-up of the Rodinia supercontinent. Magmas were erupted in rift-related basins along a strike length of at least 700 km and during a time period of c. 80 Ma. New major and trace element analyses of metabasalts from several formations are presented to trace the variations in magma compositions in time and space. The primary magmas resulted from variable degrees of mixing of melts derived from mantle sources similar to those of normal and enriched mid-ocean ridge basalts; some younger lavas also show evidence of contamination with continental crust. In contrast to speculations about magmatism elsewhere in Rodinia, the evidence here suggests that there was no involvement of a mantle plume in basalt generation. For example, the Scottish promontory of Laurentia drifted rapidly southwards through c. 25{degrees} over the duration of the magmatism, with no evidence of significant elevation above sea level, as might be expected from involvement of a plume. Generation of the primary magmas might have taken place predominantly through decompression melting in depleted upper mantle containing enriched streaks and blobs. Both the Dalradian lithostratigraphy and the metabasaltic compositions are consistent with extreme lithospheric stretching and possibly rupture during the earliest phase of magmatism, whereas generation of later magmatism appears to have been associated with major fault systems, possibly on a foundering continental margin. Supplementary materialChemical analyses of Dalradian metavolcanic rocks (major elements recalculated to 100%, anhydrous) are available at www.geolsoc.org.uk/SUP18468.

Description: : Neoproterozoic basaltic magmatism in the Dalradian Supergroup of Scotland and Ireland was associated with the break-up of the Rodinia supercontinent. Magmas were erupted in rift-related basins along a strike length of at least 700 km and during a time period of c . 80 Ma. New major and trace element analyses of metabasalts from several formations are presented to trace the variations in magma compositions in time and space. The primary magmas resulted from variable degrees of mixing of melts derived from mantle sources similar to those of normal and enriched mid-ocean ridge basalts; some younger lavas also show evidence of contamination with continental crust. In contrast to speculations about magmatism elsewhere in Rodinia, the evidence here suggests that there was no involvement of a mantle plume in basalt generation. For example, the Scottish promontory of Laurentia drifted rapidly southwards through c . 25° over the duration of the magmatism, with no evidence of significant elevation above sea level, as might be expected from involvement of a plume. Generation of the primary magmas might have taken place predominantly through decompression melting in depleted upper mantle containing enriched streaks and blobs. Both the Dalradian lithostratigraphy and the metabasaltic compositions are consistent with extreme lithospheric stretching and possibly rupture during the earliest phase of magmatism, whereas generation of later magmatism appears to have been associated with major fault systems, possibly on a foundering continental margin. Supplementary material: Chemical analyses of Dalradian metavolcanic rocks (major elements recalculated to 100%, anhydrous) are available at www.geolsoc.org.uk/SUP18468 .

Description: This paper presents the design and application of an environmental monitoring system on the historical site of Odda’s Chapel in Deerhurst, Gloucestershire, UK, and the determination of hygroscopic behaviour of the original building materials to obtain long-term moisture content variation. The monitoring system provides a comprehensive profile of hygrothermal conditions in the walls at the locations where moisture conditions are potentially causing decay and damage. The system makes use of temperature and relative humidity sensing technology placed on the wall construction, providing continuous data including rainfall, wind-driven rain and runoff rain measurements. The relative merits and results of the designed system are evaluated and discussed, as well as the implications of its application in the conservation of historical structures. The environmental monitoring results show general deterioration in the shell of the building. Internal wall surface measurements are essential for the documentation of wall interior response and should be conducted across the wall section at several locations. The fact that 91% of in-wall recorded relative humidity (RH) values are greater than 75% RH throughout the monitoring period demonstrates the need for measures to conserve this historical stone masonry.

Description: New apatite fission-track data from SE Baffin Island exhibit central ages that range from just under 200 Ma to 440 Ma, and mean track lengths that vary between c . 12 and 13.3 µm. First-order analysis of the data (a plot of central age v. mean track length) reveals an approximate ‘boomerang’ trend, typical of samples that have experienced contemporaneous cooling from an array of initial temperatures. One-dimensional inverse thermal modelling of single samples suggests that cooling through the partial annealing zone ( c . 120–60 °C) occurred over discrete periods ranging from 100 to 300 Ma. Modelling the 3D exhumation of a heterogeneous crust with flat topography demonstrates that some of the variability in observed fission-track ages could be attributed to heterogeneity in crustal heat production and thermal conductivity. The remaining variability in the observed dataset is attributed here to differential erosion from a variable initial topography. However, age discontinuities over short distances require other explanations such as faulting and/or unidentified compositional effects. Collectively, these results suggest that the observed data are consistent with a simple exhumation scenario where the present-day high topography is a remnant of that created during Palaeoproterozoic orogenies. The new data do not require any recent (Cenozoic) periods of exhumation. Supplementary material: Data locations, and isotopic and petrographic results are available at www.geolsoc.org.uk/SUP18657 .

Description: Introduction: Interphase FISH on CD138-selected bone marrow cells enables genetic risk stratification in newly diagnosed multiple myeloma (MM), however as MM remains incurable, most centres still treat newly diagnosed MM uniformly, utilising the most active regimens available. At relapse an increasing choice of regimens, coupled with co-morbidities and treatment-emergent toxicities, means no uniform approach is possible. Instead, therapy is tailored to disease and patient related risk factors. In this setting, FISH testing may be particularly useful if not done at diagnosis and to identify progression events that may alter prognosis. Aim: To evaluate the outcome of FISH analysis in consecutive patients with relapsed MM undertaken at our centre: success rate, frequency of abnormalities, incidence of progression events and correlation of FISH abnormalities with treatment outcomes. Methods: FISH analysis was performed on 192 samples from 154 relapsed patients (2012-13). Plasma cells were selected using magnetic CD138 MicroBeads and interphase FISH carried out using probes as recommended by the EMN (Ross et al, 2012). If patients had no prior results, a full FISH MM panel was performed, using probes for t(4;14), t(14;16), t(11;14), deletion 17p (17p-), Chr 1 abnormalities (1p-/1q+) and deletion 13q (13q-). If patients had been previously tested for an IgH translocation (Tx), a progression event panel was used: 1p-/1q+, 17p- and 13q-. Patients underwent FISH testing prior to starting the next line of therapy. Results: 79% of samples were successfully analysed, with analysis limited in 16% and failed in 5%. Common reasons for failure were poor quality/aged slides, insufficient material and poor hybridisation. 17% of patients had no cytogenetic abnormality. The most common abnormality was 13q- (43.1%), followed by 1q+ (41.4%), t(11;14) (18.3%), t(4;14) (12.4%), 17p- (12.0%) 1p- (8.9%), and t(14;16) (5.6%) Progression events were more common in t(14;16) and t(4;14) groups. All patients with t(14;16) and 82% with t(4;14) had an additional genetic lesion. Only 21% of patients with t(11;14) and 54% with no IgH Tx had an additional event. 80 patients (51.3%) had prior FISH results and 13 (16.3%) had developed a new abnormality on the later test. In 9 cases the progression event was 17p-, in 2 it was 1q+ and 2 cases developed 17p- and 1q+. The patients developing 1q+ were previously standard risk, so repeat testing altered risk group. Acquisition of 17p- indicates especially poor outcome, thus in all 13 cases repeat FISH analysis altered risk. Among patients with progression events none harboured t(11;14), 8 (64%) had no IgH Tx, 3 had t(14;16) and 2 had t(4;14). FISH results were correlated with clinical outcome. Patients were stratified as having high risk genetics [t(4;14), t(14,16), 17p- in ≥50% cells, 1p-/1q+] or standard risk [t(11;14), normal cytogenetics]. 63 (41%) patients were high risk, 83 (54%) standard risk, with no information available for 8 (5%). Both groups had received a median of 2 prior lines of therapy. Response rates (≥PR) to the next line of therapy were similar (60.4% standard risk vs 56.0% high risk). PFS from time of FISH was significantly longer in the standard risk group (9.8 months vs 5.9, p

Description: Abstract 2187 Plasma cells, the terminal effectors of the B-cell lineage include both short- and long-lived cells. The latter persist for extended periods in the absence of cell division, supported in niche environments. No model system has successfully recapitulated the function of the niche to allow the in vitro generation of long-lived plasma cells. This limits investigation into the factors controlling and targeting plasma cell populations. Here we describe the generation of mature human plasma cells with extended lifespan from peripheral blood B-cells. Cell division accompanies phenotypic maturation between plasmablasts and plasma cells. These cells then persist in the absence of cell division, remaining functional and viable in extended culture, currently limited solely by elective termination. Extended survival is accompanied by maturation to a phenotype consistent with human bone marrow plasma cells. By establishing a set of conditions sufficient to allow the development and persistence of mature human plasma cells in vitro, we recapitulate the essential function of the plasma cell niche. We definitively link phenotypic maturation to lifespan and provide the first platform with which to explore and manipulate the full trajectory of human plasma cell differentiation. Disclosures: No relevant conflicts of interest to declare.

Description: Background:Flow cytometric studies are useful in the diagnostic workup of patients with unexplained cytopenias and it has been demonstrated that bone marrow aspirates with immunophenotypic abnormalities by flow cytometry but not diagnostic morphologic or cytogenetic findings frequently evolve into myelodysplastic syndromes (MDS) (Kern 2013). Two flow cytometric scoring systems (FCSSs), the Wells FCSS and the Ogata FCSS, have diagnostic and prognostic utility. The Wells FCSS utilizes a difference from normal algorithm incorporating more than ten phenotypic parameters. The accumulation of these abnormalities is not only useful in diagnosis but is predictive of patient outcome (Wells 2003, Scott 2008, Alhan 2014). The recommended Ogata FCSS has evolved to include four cardinal parameters: (1) CD45 intensity on the myeloid progenitors, (2) frequency of lymphoblasts, (3) frequency of myeloid progenitors, and (4) granularity of the maturing myeloid cells. The Wells FCSS is more comprehensive as it uses more phenotypic characteristics, while the Ogata score is considered straightforward to implement in a routine setting (Della Porta 2012, Ogata 2009). This study compares the Wells FCSS and Ogata FCSS for sensitivity and specificity to detect clonal abnormalities documented by SNP/CGH microarray and conventional cytogenetics. Patients and Methods: The cohort included 99 patients with unexplained cytopenias whose bone marrow aspirates were submitted for SNP/CGH microarray and flow cytometry (HematoLogics). The immunophenotypic data were independently assigned a Wells FCSS (Cutler 2012) and an Ogata FCSS (Della Porta 2012). SNP/CGH microarray was assessed for MDS-associated genetic abnormalities. The findings were further correlated with conventional cytogenetic findings. Results: Of the 99 bone marrow aspirates, 20 exhibited clonal abnormalities associated with MDS. The Wells FCSS identified immunophenotypic abnormalities suggestive of MDS for 18 of 20 CGH positive specimens (sensitivity of 90%) and did not detect phenotypic abnormalities suggestive of MDS in 68 of 79 CGH negative specimens (specificity of 86%). In contrast the Ogata FCSS identified immunophenotypic abnormalities suggestive of MDS for 13 of 20 CGH positive specimens (sensitivity of 65%) and did not detect phenotypic abnormalities suggestive of MDS in 64 of 79 the CGH negative specimens (specificity of 81%). In an attempt to improve the sensitivity and specificity of the Ogata score, the granularity parameter was modified from side scatter channel mode of the granulocytes (compared to the side scatter mode of the lymphocytes) to the side scatter channel at the 15thpercentile of granulocytes (compared to the mean of lymphocytes). This modified parameter detected all specimens defined as hypogranular by the side scatter mode, and detected an additional 11 specimens as hypogranular. All of these specimens were detected as hypogranular by the Wells definition. This modified granularity method was then used along with the other three cardinal parameters to create a modified Ogata FCSS. The granularity modification resulted in improved sensitivity (70% versus 65%); specificity was unchanged. While the modified method outperformed the original, it did not match the performance of the Wells FCSS. Conclusions: In patients with unexplained cytopenias, the Wells FCSS demonstrates superior specificity and sensitivity than the Ogata FCSS for detecting myeloid immunophenotypic clones associated with SNP/CGH array and cytogenetic abnormalities. Modifying the Ogata granularity parameter marginally improves the sensitivity but does not improve the specificity. Implementation of the Wells FCSS requires a comprehensive understanding of phenotypic intensities and relationships in non-clonal hematopoiesis for patients with cytopenias. While the relative ease of implementing the Ogata FCSS is attractive, improvements are essential for diagnostic accuracy; improving the granularity parameter alone is not sufficient. Adding measurements for the maturing myeloid and erythroid compartments may increase the diagnostic utility of the Ogata FCSS but requires further study. Disclosures Brodersen: Hematologics Inc.: Employment. Menssen:Hematologics Inc.: Employment. Zehentner:HematoLogics Inc.: Employment, Equity Ownership. Stephenson:Hematologics Inc.: Employment. de Baca:Hematologics Inc.: Employment. Johnson:Hematologics Inc.: Employment. Singleton:Hematologics Inc.: Employment. Hartmann:Hematologics Inc.: Employment. Loken:Hematologics: Employment, Equity Ownership. Wells:HematoLogics Inc.: Employment, Equity Ownership.