Risk Prediction for Epithelial Ovarian Cancer in 11 United States-Based Case-Control Studies: Incorporation of Epidemiologic Risk Factors and 17 Confirmed Genetic Loci.

Previously developed models for predicting absolute risk of invasive epithelial ovarian cancer have included a limited number of risk factors and have had low discriminatory power (area under the receiver operating characteristic curve (AUC) < 0.60). Because of this, we developed and internally validated a relative risk prediction model that incorporates 17 established epidemiologic risk factors and 17 genome-wide significant single nucleotide polymorphisms (SNPs) using data from 11 case-control studies in the United States (5,793 cases; 9,512 controls) from the Ovarian Cancer Association Consortium (data accrued from 1992 to 2010). We developed a hierarchical logistic regression model for predicting case-control status that included imputation of missing data. We randomly divided the data into an 80% training sample and used the remaining 20% for model evaluation. The AUC for the full model was 0.664. A reduced model without SNPs performed similarly (AUC = 0.649). Both models performed better than a baseline model that included age and study site only (AUC = 0.563). The best predictive power was obtained in the full model among women younger than 50 years of age (AUC = 0.714); however, the addition of SNPs increased the AUC the most for women older than 50 years of age (AUC = 0.638 vs. 0.616). Adapting this improved model to estimate absolute risk and evaluating it in prospective data sets is warranted.

Thorium and Uranium analyses of sediment core GIK12310-4, NW African continental margin (Table 1,2)

The Th content of the sediment samples from "Meteor" core GIK12310-4 (3080 m water depth, off NW Africa) on a carbonate-free basis lies around the average of 12.4 ppm and is similar to the average content of the earth crust. On the contrary, uranium was found to be up to 3.5-fold enriched in the core section between 60 and 330 cm (within the Wuerm Glacial) where reducing conditions occur, due to deposition of authigenic uranium (9 µg/cm**2 1000 yrs.). The authigenic uranium content is correlated to the organic matter content (U/Corg ratio = 6 * 10**4). On the basis of the uranium content of the oxidized section uranium was split into a detritic and an authigenic component and the amount of supported ionium was calculated. From the profile of the specific Io-cxcess activity (= Io-total - Io-supported) with depth, average sedimentation rates of 3.3 ± 0.6 cm/1000 yrs. for the warmer stages and of 5 ± 1 cm/l000 yrs. for the cooler periods were estimated.

Phosphorus geochemistry of eastern equatorial Pacific Ocean sediments

We determined phosphorus (P) concentrations in Leg 138 sediment samples from Sites 844, 846, and 851, using a sequential extraction technique to identify the P associated with five sedimentary components. Total concentrations of P (sum of the five components) ranged from 4 to 35 µmol P/g sediment, with mean values relatively similar between the three sites (11, 14, and 12 for Sites 844,846, and 851, respectively). Authigenic/biogenic P was the most important component in terms of percentage of total P (about 75%), with iron-bound P (13%), adsorbed P (2%-9%), and organic P (4%) of secondary importance; detrital P was a minor P sink (1%) in these sediments. Profiles of adsorbed P and iron-bound P show decreasing concentrations with age, indicating that these components have been affected by diagenesis and reorganization of P. A peak in iron-bound P may reflect higher fluxes of hydrothermally derived Fe to eastern equatorial Pacific Ocean sediments from 11 to 8 Ma. Lower detrital P values for western Site 851 reflect a greater distance of this site from a terrigenous source area, compared to that of Sites 844 and 846. Phosphorus mass accumulation rates (P-MARs; units of µmol P/cm**2/k.y.) were calculated using total P concentrations (not including the minor and oceanically unreactive detrital P component) and sedimentation rates and dry-bulk densities averaged over time intervals of 0.5 m.y. P-MARs generally decrease from 17 Ma to the present. Eastern transect Sites 844 and 846 display a decrease in P-MARs from about 30 to 10 in the interval from 17 to 8 Ma, while western transect Site 851 is highly variable during this interval. P-MARs increase to about 45 and stay relatively high from 8 to 6 Ma, then decrease toward the present to some of the lowest values of the record (about 10). The general trend of high P-MARs at about 6 Ma and decreasing values toward the present is correlated with other geochemical and sedimentary trends through this interval and may reflect (1) a change in net sediment and P burial, (2) a reorganization of fluxes with no change of net burial, or (3) a combination of the two.

Stable isotopes of benthic foraminifera from Site ODP 184-1146

We generated a high resolution (~8 ky) benthic record from a West Pacific marginal basin to investigate the detailed structure and spectral characteristics of deep water isotope fluctuations during the middle Miocene. The benthic record from ODP Site 1146 allows unprecedented resolution of the structure of the middle Miocene delta13C excursion, as well as tighter control on the chronology of climatic events. Spectral analysis of the variance in the delta18O and delta13C records from ODP Site 1146 reveals spectral power concentrated in the eccentricity band (400-, ~100-ky) over the time interval between 13 and 17 Ma. The amplitude evolution in the 400-ky band is strikingly similar to that of the long eccentricity in Laskar's solution. There is an abrupt switch to the obliquity band in the delta18O record at -14.9 Ma, suggesting a shift in the ocean/climate response to orbital forcing (from low latitude eccentricity to high latitude obliquity forcing). The obliquity signal is pervasive in the delta18O record until -13.9 Ma, when a sharp increase in delta18O values indicates a major climatic transition. Comparison of delta18O and delta13C profiles from DSDP Site 588 (SW Pacific Ocean), ODP Site 761 (E Indian Ocean) and ODP Site 1146 (South China Sea) reveals significantly cooler deep water in the NE Indian Ocean throughout the middle Miocene and a restricted deep water exchange between the Pacific Ocean and Indian Ocean.

Conventional and 40Ar/39Ar K-Ar ages of volcanic rocks at DSDP Leg 55 Holes

Conventional K-Ar, 40Ar/39Ar total fusion, and 40Ar/39Ar incremental heating data on hawaiite and tholeiitic basalt samples from Ojin (Site 430), alkalic basalt samples from Nintoku (Site 432), and alkalic and tholeiitic basalt samples from Suiko (Site 433) seamounts in the Emperor Seamount chain give the following best ages for these volcanoes: Ojin = 55.2 ± 0.7 m.y., Nintoku = 56.2 ± 0.6 m.y., and Suiko = 64.7 ± 1.1 m.y. These new data bring to 27 the number of dated volcanoes in the Hawaiian-Emperor volcanic chain. The new dates prove that the age progression from Kilauea Volcano on Hawaii (0 m.y.) through the Hawaiian-Emperor bend (- 43 m.y.) to Koko Seamount (48.1 m.y.) in the southernmost Emperor Seamounts continues more than halfway up the Emperor chain to Suiko Seamount. The age versus distance data for the Hawaiian-Emperor chain are consistent with the kinematic hot-spot hypothesis, which predicts that the volcanoes are progressively older west and north away from the active volcanoes of Kilauea and Mauna Loa. The data are consistent with an average volcanic propagation velocity of either 8 cm/year from Suiko to Kilauea or of 6 cm/year from Suiko to Midway followed by a velocity of 9 cm/year from Midway to Kilauea, but it appears that the change in direction that formed the Hawaiian- Emperor bend probably was not accompanied by a major change in velocity.

(Table 2) Carbonate chemistry and isotopes from northern Cascadia margin samples

Most authigenic carbonates previously recovered from the Cascadia slope have 87Sr/86Sr signatures that reflect shallow precipitation in equilibrium with coeval seawater. There is also evidence for carbonate formation supported by fluids that have been modified by reactions with the incoming Juan de Fuca plate (87Sr/86Sr = 0.7071; Teichert et al., 2005, doi:10.1016/j.epsl.2005.08.002) or with terrigenous turbidites (87Sr/86Sr = 0.70975 to 0.71279; Sample et al., 1993, doi:10.1130/0091-7613(1993)021<0507:CCICFF>2.3.CO;2). We report on the strontium isotopic composition of carbonates and fluids from IODP Site U1329 and nearby Barkley Canyon (offshore Vancouver Island), which have strontium isotope ratios as low as 0.70539. Whereas the strontium and oxygen isotopic compositions of carbonates from paleoseeps in the uplifted Coast Range forearc indicate formation in ambient bottom seawater, several samples from the Pysht/Sooke Fm. show a 87Sr-depleted signal (87Sr/86Sr = 0.70494 and 0.70511) similar to that of the anomalous Site U1329 and Barkley Canyon carbonates. Our data, when analyzed in the context of published elemental and isotopic composition of these carbonates (Joseph et al., 2012, doi:10.1016/j.palaeo.2013.01.012 ), point to two formation mechanisms: 1) shallow precipitation driven by the anaerobic oxidation of methane (AOM) with d13C values as low as -50 per mil and contemporaneous 87Sr/86Sr seawater ratios, and 2) carbonate precipitation driven by fluids that have circulated through the oceanic crust, which are depleted in 87Sr. Carbonates formed from the second mechanism precipitate both at depth and at sites of deep-sourced fluid seepage on the seafloor. The 87Sr-depleted carbonates and pore fluids found at Barkley Canyon represent migration of a deep, exotic fluid similar to that found in high permeability conglomerate layers at 188 mbsf of Site U1329, and which may have fed paleoseeps in the Pysht/Sooke Fm. These exotic fluids likely reflect interaction with the 52-57 Ma igneous Crescent Terrane, which supplies fluids with high calcium, manganese and strontium enriched in the non-radiogenic nucleide. Tectonic compression and dehydration reactions then force these fluids updip, where they pick up the thermogenic hydrocarbons and 13C-enriched dissolved inorganic carbon that are manifested in fluids and carbonates sampled at Barkley Canyon and at Site U1329. The Crescent Terrane may have sourced cold seeps in this margin since at least the late Oligocene.

Mineralogical, geochemical and magnetic signatures of surface sediments from the Canadian Beaufort Shelf and Amundsen Gulf (Canadian Arctic)

Mineralogical, geochemical, magnetic, and siliciclastic grain-size signatures of 34 surface sediment samples from the Mackenzie-Beaufort Sea Slope and Amundsen Gulf were studied in order to better constrain the redox status, detrital particle provenance, and sediment dynamics in the western Canadian Arctic. Redox-sensitive elements (Mn, Fe, V, Cr, Zn) indicate that modern sedimentary deposition within the Mackenzie-Beaufort Sea Slope and Amundsen Gulf took place under oxic bottom-water conditions, with more turbulent mixing conditions and thus a well-oxygenated water column prevailing within the Amundsen Gulf. The analytical data obtained, combined with multivariate statistical (notably, principal component and fuzzy c-means clustering analyses) and spatial analyses, allowed the division of the study area into four provinces with distinct sedimentary compositions: (1) the Mackenzie Trough-Canadian Beaufort Shelf with high phyllosilicate-Fe oxide-magnetite and Al-K-Ti-Fe-Cr-V-Zn-P contents; (2) Southwestern Banks Island, characterized by high dolomite-K-feldspar and Ca-Mg-LOI contents; (3) the Central Amundsen Gulf, a transitional zone typified by intermediate phyllosilicate-magnetite-K-feldspar-dolomite and Al-K-Ti-Fe-Mn-V-Zn-Sr-Ca-Mg-LOI contents; and (4) mud volcanoes on the Canadian Beaufort Shelf distinguished by poorly sorted coarse-silt with high quartz-plagioclase-authigenic carbonate and Si-Zr contents, as well as high magnetic susceptibility. Our results also confirm that the present-day sedimentary dynamics on the Canadian Beaufort Shelf is mainly controlled by sediment supply from the Mackenzie River. Overall, these insights provide a basis for future studies using mineralogical, geochemical, and magnetic signatures of Canadian Arctic sediments in order to reconstruct past variations in sediment inputs and transport pathways related to late Quaternary climate and oceanographic changes.

Boron isotope composition and seawater characteristics of cold water scleratinian corals

The boron isotope systematics has been determined for azooxanthellate scleractinian corals from a wide range of both deep-sea and shallow-water environments. The aragonitic coral species, Caryophyllia smithii, Desmophyllum dianthus, Enallopsammia rostrata, Lophelia pertusa, and Madrepora oculata, are all found to have relatively high d11B compositions ranging from 23.2 per mil to 28.7 per mil. These values lie substantially above the pH-dependent inorganic seawater borate equilibrium curve, indicative of strong up-regulation of pH of the internal calcifying fluid (pH(cf)), being elevated by ~0.6-0.8 units (Delta pH) relative to ambient seawater. In contrast, the deep-sea calcitic coral Corallium sp. has a significantly lower d11B composition of 15.5 per mil, with a corresponding lower Delta pH value of ~0.3 units, reflecting the importance of mineralogical control on biological pH up-regulation. The solitary coral D. dianthus was sampled over a wide range of seawater pH(T) and shows an approximate linear correlation with Delta pH(Desmo) = 6.43 - 0.71 pH(T) (r**2 = 0.79). An improved correlation is however found with the closely related parameter of seawater aragonite saturation state, where Delta pH(Desmo) = 1.09 - 0.14 Omega(arag) (r**2 = 0.95), indicating the important control that carbonate saturation state has on calcification. The ability to up-regulate internal pH(cf), and consequently Omega(cf), of the calcifying fluid is therefore a process present in both azooxanthellate and zooxanthellate aragonitic corals, and is attributed to the action of Ca2+ -ATPase in modulating the proton gradient between seawater and the site of calcification. These findings also show that the boron isotopic compositions (d11Bcarb) of aragonitic corals are highly systematic and consistent with direct uptake of the borate species within the biologically controlled extracellular calcifying medium.

Bulk sediment parameters and coarse-fraction analysis of ODP Leg 178 holes

The area west of the Antarctic Peninsula is a key region for studying and understanding the history of glaciation in the southern high latitudes during the Neogene with respect to variations of the western Antarctic continental ice sheet, variable sea-ice cover, induced eustatic sea level change, as well as consequences for the global climatic system (Barker, Camerlenghi, Acton, et al., 1999). Sites 1095, 1096, and 1101 were drilled on sediment drifts forming the continental rise to examine the nature and composition of sediments deposited under the influence of the Antarctic Peninsula ice sheet, which has repeatedly advanced to the shelf edge and subsequently released glacially eroded material on the continental shelf and slope (Barker et al., 1999). Mass gravity processes on the slope are responsible for downslope sediment transport by turbidity currents within a channel system between the drifts. Furthermore, bottom currents redistribute the sediments, which leads to final build up of drift bodies (Rebesco et al., 1998). The high-resolution sedimentary sequences on the continental rise can be used to document the variability of continental glaciation and, therefore, allow us to assess the main factors that control the sediment transport and the depositional processes during glaciation periods and their relationship to glacio-eustatic sea level changes. Site 1095 lies in 3840 m of water in a distal position on the northwestern lower flank of Drift 7, whereas Site 1096 lies in 3152 m of water in a more proximal position within Drift 7. Site 1101 is located at 3509 m water depth on the northwestern flank of Drift 4. All three sites have high sedimentation rates. The oldest sediments were recovered at Site 1095 (late Miocene; 9.7 Ma), whereas sediments of Pliocene age were recovered at Site 1096 (4.7 Ma) and at Site 1101 (3.5 Ma). The purpose of this work is to provide a data set of bulk sediment parameters such as CaCO3, total organic carbon (TOC), and coarse-fraction mass percentage (>63 µm) measured on the sediments collected from the continental rise of the western Antarctic Peninsula (Holes 1095A, 1095B, 1096A, 1096B, 1096C, and 1101A). This information can be used to understand the complex depositional processes and their implication for variations in the climatic system of the western Pacific Antarctic margin since 9.7 Ma (late Miocene). Coarse-fraction particles (125-500 µm) from the late Pliocene and Pleistocene (4.0 Ma to recent) sediments recovered from Hole 1095A were microscopically analyzed to gather more detailed information about their variability and composition through time. These data can yield information about changes in potential source regions of the glacially eroded material that has been transported during repeated periods of ice-sheet movements on the shelf.

Occurrence of microtextures recorded from quartz sand grains of ODP Hole 178-1101A (Table 1)

Sediment drifts on the continental rise are located proximal to the western side of the Antarctic Peninsula and recorded changes in glacial volume and thermal regime over the last ca. 15 m.y. At Ocean Drilling Program (ODP) Site 1101 (Leg 178), which recovered sediments back to 3.1 Ma, glacial-interglacial cyclicity was identified based on the biogenic component and sedimentary structures observed in X-radiographs, magnetic susceptibility and lithofacies descriptions. Glacial intervals are dominated by fine-grained laminated mud and interglacial units consist of bioturbated muds enriched in biogenic components. From 2.2 to 0.76 Ma, planktonic foraminifera and calcareous nannofossils dominate in the interglacials suggesting a shift of the Antarctic Polar Front (APF) to the south near the drifts. Prior to 2.2 Ma, cyclicity cannot be identified and diatoms dominate the biogenic component and high percent opal suggests warmer conditions south of the APF and reduced sea ice over the drifts. Analyses of the coarse-grained terrigenous fraction (pebbles and coarse sand) from Sites 1096 and 1101 record glaciers at sea-level releasing iceberg-rafted debris (IRD) throughout the last 3.1 m.y. Analyses of quartz sand grains in IRD with the scanning electron microscope (SEM) show an abrupt change in the frequency of occurrence of microtextures at ~1.35 Ma. During the Late Pliocene to Early Pleistocene, the population of quartz grains included completely weathered grains and a low frequency of crushing and abrasion, suggesting that glaciers were small and did not inundate the topography. Debris shed from mountain peaks was transported supraglacially or englacially allowing weathered grains to pass through the glacier unmodified. During glacial periods from 1.35-0.76 Ma, glaciers expanded in size. The IRD flux was very high and dropstones have diverse lithologies. Conditions resembling those at the Last Glacial Maximum (LGM) have been episodically present on the Antarctic Peninsula since ~0.76 Ma. Quartz sand grains show high relief, fracture and abrasion common under thick ice and the IRD flux is low with a more restricted range of dropstone lithologies.

Descriptions of Scottish Priority Marine Features (PMFs).

Background The seas around Scotland are rich and diverse – Scotland’s position at the edge of the continental shelf, the long coastline, large area of sea and the mixing of warm and coldwater currents combine to make its waters a special place for marine wildlife and habitats. Scotland has over 18,000 km of coastline and its inshore and offshore areas are among the largest of any EU country, representing 13% of all European seas. Scotland’s seas are of outstanding scenic, historical and cultural value and are part of the national identity at home and abroad. The Marine (Scotland) Act 2010 and the UK Marine and Coastal Access Act 2009 include new powers and duties to ensure that our seas are managed sustainably for future generations, integrating the economic growth of marine industries with the need to protect these assets. Measures to conserve Scotland’s marine natural heritage are based on a three pillar approach, with action at the wider seas level (e.g. marine planning or sectoral controls); specific species conservation measures (e.g. improved protection for seals); and through site protection measures - the identification of new Marine Protected Areas (MPAs). To help target action under each of the three pillars, Scottish Natural Heritage (SNH) and the Joint Nature Conservation Committee (JNCC) have generated a focused list of habitats and species of priority conservation importance - the Priority Marine Features (PMFs). The aim of the current study was to produce a descriptive catalogue of the Scottish PMFs (including component habitats and species where appropriate) to serve as a reference for future nature conservation action. Whilst derived from available existing accounts, the succinct 1-page descriptions are written from a Scottish perspective, refining, but clearly linking to more generic UK, EC or OSPAR (Oslo and Paris Commission) commentary. Available information on the geographic distribution of the features was collated as part of the project and a summary map is provided in each description. Main findings  This project has generated a descriptive catalogue of the 81 PMFs that have been identified in the seas around Scotland (out to the limit of the UK continental shelf). The list comprises 26 broad habitats (e.g. burrowed mud), seven low or limited mobility species (e.g. ocean quahog) and 48 mobile species, including fish (e.g. blue ling) and marine mammals (e.g. minke whale).  Information on the distribution of the PMFs was collated within a Geographic Information System (GIS). This is the first time that data about such a diverse range of Scottish marine nature conservation interests have been compiled within a single repository. These data have and will be used in conjunction with other contextual base-mapping to inform the development of nature conservation advice and commentary (e.g. in the production of the Scotland’s Marine Atlas - Baxter et al., 2011).  The feature distribution mapping used in the production of this report is being made available to view online via the National Marine Plan Interactive web portal (NMPi - http://www.gov.scot/Topics/marine/seamanagement/nmpihome). As new or refined data on Scottish PMFs become available, these will be fed into updates to the project geodatabase and NMPi.

Descriptions of Scottish Priority Marine Features (PMFs).

Background The seas around Scotland are rich and diverse – Scotland’s position at the edge of the continental shelf, the long coastline, large area of sea and the mixing of warm and coldwater currents combine to make its waters a special place for marine wildlife and habitats. Scotland has over 18,000 km of coastline and its inshore and offshore areas are among the largest of any EU country, representing 13% of all European seas. Scotland’s seas are of outstanding scenic, historical and cultural value and are part of the national identity at home and abroad. The Marine (Scotland) Act 2010 and the UK Marine and Coastal Access Act 2009 include new powers and duties to ensure that our seas are managed sustainably for future generations, integrating the economic growth of marine industries with the need to protect these assets. Measures to conserve Scotland’s marine natural heritage are based on a three pillar approach, with action at the wider seas level (e.g. marine planning or sectoral controls); specific species conservation measures (e.g. improved protection for seals); and through site protection measures - the identification of new Marine Protected Areas (MPAs). To help target action under each of the three pillars, Scottish Natural Heritage (SNH) and the Joint Nature Conservation Committee (JNCC) have generated a focused list of habitats and species of priority conservation importance - the Priority Marine Features (PMFs). The aim of the current study was to produce a descriptive catalogue of the Scottish PMFs (including component habitats and species where appropriate) to serve as a reference for future nature conservation action. Whilst derived from available existing accounts, the succinct 1-page descriptions are written from a Scottish perspective, refining, but clearly linking to more generic UK, EC or OSPAR (Oslo and Paris Commission) commentary. Available information on the geographic distribution of the features was collated as part of the project and a summary map is provided in each description. Main findings  This project has generated a descriptive catalogue of the 81 PMFs that have been identified in the seas around Scotland (out to the limit of the UK continental shelf). The list comprises 26 broad habitats (e.g. burrowed mud), seven low or limited mobility species (e.g. ocean quahog) and 48 mobile species, including fish (e.g. blue ling) and marine mammals (e.g. minke whale).  Information on the distribution of the PMFs was collated within a Geographic Information System (GIS). This is the first time that data about such a diverse range of Scottish marine nature conservation interests have been compiled within a single repository. These data have and will be used in conjunction with other contextual base-mapping to inform the development of nature conservation advice and commentary (e.g. in the production of the Scotland’s Marine Atlas - Baxter et al., 2011).  The feature distribution mapping used in the production of this report is being made available to view online via the National Marine Plan Interactive web portal (NMPi - http://www.gov.scot/Topics/marine/seamanagement/nmpihome). As new or refined data on Scottish PMFs become available, these will be fed into updates to the project geodatabase and NMPi.

GIS technologies and spatial organization patterns among hunter-gatherers: an archaeological case study from Southern Patagonia (southern South America)

This paper discusses some aspects of hunter-gatherer spatial organization in southern South Patagonia, in later times to 10,000 cal yr BP. Various methods of spatial analysis, elaborated with a Geographic Information System (GIS) were applied to the distributional pattern of archaeological sites with radiocarbon dates. The shift in the distributional pattern of chronological information was assessed in conjunction with other lines of evidence within a biogeographic framework. Accordingly, the varying degrees of occupation and integration of coastal and interior spaces in human spatial organization are explained in association with the adaptive strategies hunter-gatherers have used over time. Both are part of the same human response to changes in risk and uncertainty variability in the region in terms of resource availability and environmental dynamics.

RAGE Reusable Game Software Components and Their Integration into Serious Game Engines

This paper presents and validates a methodology for integrating reusable software components in diverse game engines. While conforming to the RAGE com-ponent-based architecture described elsewhere, the paper explains how the interac-tions and data exchange processes between a reusable software component and a game engine should be implemented for procuring seamless integration. To this end, a RAGE-compliant C# software component providing a difficulty adaptation routine was integrated with an exemplary strategic tile-based game “TileZero”. Implementa-tions in MonoGame, Unity and Xamarin, respectively, have demonstrated successful portability of the adaptation component. Also, portability across various delivery platforms (Windows desktop, iOS, Android, Windows Phone) was established. Thereby this study has established the validity of the RAGE architecture and its un-derlying interaction processes for the cross-platform and cross-game engine reuse of software components. The RAGE architecture thereby accommodates the large scale development and application of reusable software components for serious gaming.

Incidence and clinicobiologic characteristics of leukemic B-cell chronic lymphoproliferative disorders with more than one B-cell clone.

Leukemic B-chronic lymphoproliferative disorders (B-CLPDs) are generally believed to derive from a monoclonal B cell; biclonality has only occasionally been reported. In this study, we have explored the incidence of B-CLPD cases with 2 or more B-cell clones and established both the phenotypic differences between the coexisting clones and the clinicobiologic features of these patients. In total, 53 B-CLPD cases with 2 or more B-cell clones were studied. Presence of 2 or more B-cell clones was suspected by immunophenotype and confirmed by molecular/genetic techniques in leukemic samples (n = 42) and purified B-cell subpopulations (n = 10). Overall, 4.8% of 477 consecutive B-CLPDs had 2 or more B-cell clones, their incidence being especially higher among hairy cell leukemia (3 of 13), large cell lymphoma (2 of 10), and atypical chronic lymphocytic leukemia (CLL) (4 of 29). In most cases the 2 B-cell subsets displayed either different surface immunoglobulin (sIg) light chain (n = 37 of 53) or different levels of the same sIg (n = 9 of 53), usually associated with other phenotypic differences. Compared with monoclonal cases, B-CLL patients with 2 or more clones had lower white blood cell (WBC) and lymphocyte counts, more frequently displayed splenomegaly, and required early treatment. Among these, the cases in which a CLL clone coexisted with a non-CLL clone were older and more often displayed B symptoms, a monoclonal component, and diffuse infiltration of bone marrow and required early treatment more frequently than cases with monoclonal CLL or 2 CLL clones.