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Background The Myeloma XI study is the first randomized study to investigate a response-adapted approach to induction therapy for newly diagnosed myeloma (NDMM). The study addresses whether, for patients achieving less than optimum response to an initial immunomodulatory (IMiD) triplet combination, defined as at least VGPR, the use of a sequential proteasome inhibitor (PI) based triplet can improve outcomes. In total 581 patients were randomized into the study which confirms the clinically significant benefit of deepening responses by utilizing treatment with a different mode of action, and that this leads to better outcomes. Methods This phase III, UK-based, multicenter, open-label, parallel group, randomized controlled trial for NDMM patients of all ages, randomized patients initially between a thalidomide or lenalidomide triplet combination with cyclophosphamide and dexamethasone. This IMiD triplet was continued for a minimum of 4 cycles (transplant eligible, TE) or 6 cycles (transplant non-eligible, TNE) and to maximum response. At the end of this IMiD regimen response was assessed. Patients with a suboptimal response (MR/PR) were randomized between further induction therapy with bortezomib, cyclophosphamide and dexamethasone (CVD) or no further induction therapy. Patients with a good response (VGPR/CR) proceeded straight to ASCT (if TE), whilst refractory (SD/PD) patients all received the CVD regimen. For patients receiving CVD, treatment was planned to continue to maximum response, and eligible patients would proceed to ASCT. The primary endpoints of the adapted approach randomization were progression-free survival (PFS) and overall survival. Secondary endpoints included upgrading of response compared to baseline and the impact of the PI combination in a high-risk subgroup. This abstract contains a preliminary analysis, final data will be presented at the meeting. The median follow up in this analysis is 29 months [IQR 17-44]. Results 581 patients (366 TE, 215 TNE) with initial response to IMiD of MR/PR were entered into the CVD randomization. In total 292/581 patients were randomized to receive sequential treatment with CVD. The arms were well-balanced with respect to clinical features and response (e.g. ISS stage: III 21% vs 19%, PR: 88% vs 88%). This randomization has met its primary endpoint. Overall the sequential use of CVD significantly improved PFS from a median of 24 to 30 months (HR 0.67 [95%CI 0.53-0.85], p=0.0005). This was largely due to a significant improvement seen in the TE pathway, HR 0.56 [95%CI 0.40-0.77], median PFS no therapy 31 months vs CVD 55 months, p=0.0003. In the TNE pathway there was an early benefit with improved median PFS 14 months vs 20 months, but similar hazard after 2 years (HR 0.83 [95%CI 0.60-1.17], p=0.297). Importantly upgrading of response was seen with 118/289 (41% [95%CI 35-47]) of evaluable patients who received CVD moving from MR/PR to VGPR/CR. 115/289 remained in the same response category MR/PR, but these patients still had a mean reduction in paraprotein during CVD of 24% [95%CI 11-17]. The upgrade in response was seen in both pathways and was not affected by the IMiD received in the initial induction randomization. The impact of CVD in cases with molecularly defined high-risk disease compared to standard and multiparameter flow cytometry assessment of minimal residual disease status will be presented at the meeting. In the transplant eligible pathway an improved depth of response persisted in the 253 patients completing ASCT with VGPR/CR responses post ASCT of 65% for those who were randomized to CVD (VGPR n=133, CR n=86) compared to 38% for those who went straight to transplant (VGPR n=120, CR n=46). Sequential CVD was well tolerated with patients receiving a median of 4 cycles of therapy (range 1-8). Relevant grade 3/4 toxicities were: neutropenia 7.1%, thrombocytopenia 7.5%, anaemia 3.1%, peripheral neuropathy 5.1%. Conclusion For the first time we have shown that the use of a response-adapted therapy based on the use of chemotherapeutic agents with a different mode of action in myeloma can improve response rates, both pre- and post-transplant and that these translate into improved PFS. On behalf of the NCRI Haem-Onc CSG Disclosures Jackson: Roche: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau. Davies:Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Pawlyn:Celgene: Consultancy, Honoraria, Other: Travel Support; Takeda Oncology: Consultancy. Jones:Celgene: Honoraria, Research Funding. Kishore:celgene: Other: travel grant. Garg:Janssen: Other: Travel support, Research Funding, Speakers Bureau; Takeda: Other: Travel support; Novartis: Other: Travel support, Research Funding. Williams:Takeda: Honoraria, Other: Travel support, Speakers Bureau; Janssen: Honoraria, Other: Travel support, Speakers Bureau; Celgene: Honoraria, Other: Travel support, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Novartis: Honoraria. Karunanithi:Celgene: Other: Travel support, Research Funding; Janssen: Other: Travel support, Research Funding. Lindsay:Novartis: Other: Travel support; Janssen: Consultancy; Takeda: Other: Travel support; BMS: Consultancy, Other: Travel support; Celgene: Honoraria, Other: Travel support. Jenner:Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel support, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel support; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Other: Travel support. Cook:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria; Glycomimetics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Kaiser:BMS: Consultancy, Other: Travel Support; Takeda: Consultancy, Other: Travel Support; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Chugai: Consultancy. Drayson:Abingdon Health: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Owen:Takeda: Honoraria, Other: Travel support; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Other: Travel support. Morgan:Bristol Meyers: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Research Funding; Univ of AR for Medical Sciences: Employment; Celgene: Consultancy, Honoraria, Research Funding.

Introduction. Minimal residual disease (MRD) is a powerful predictor of outcome in multiple myeloma (MM). We have previously demonstrated, in transplant eligible patients, that the level of MRD as a continuous variable independently predicts both PFS and OS, with approximately a one year median OS benefit per log depletion (J Clin Oncol 2013; 31:2540-7 and Blood 2015; 125:1932-5). The impact of MRD also appears to be independent of therapy received. There is more limited data on the applicability of MRD assessment in transplant ineligible patients, largely as a consequence of low rates of CR historically within this patient cohort. Patients and Methods. In this analysis we have assessed the impact of MRD on PFS amongst patients treated within the non-intensive arm of the NCRI Myeloma XI trial. Patients were randomised between thalidomide (CTDa) and lenalidomide (RCDa) based induction therapies with responding patients being subsequently randomised to maintenance with lenalidomide monotherapy, or no further therapy. Bone marrow aspirates were obtained at the end of induction and this analysis represents a subset of 297 patients (median age 74 years). MRD was assessed using flow cytometry (sensitivity 10-4) with a minimum of 500,000 cells evaluated with six-colour antibody combinations including CD138/CD38/CD45/CD19 with CD56/CD27 in all cases and CD81/CD117 in additional cases as required. Results. Overall MRD-negativity was demonstrated in 41/297 (13.8%). When considered according to induction therapy received 25/154 (16.0%) of patients randomized to RCDa were MRD-negative compared to 16/143 (10.8%) of those randomized to CTDa (p=0.24; Fisher's exact test). MRD-negativity was associated with a significant outcome advantage as the median PFS was 34 months versus 18 months for MRD-positive patients (p/=10% were 34, 26, 16, 14 and 9 months respectively (p Conclusions. We would conclude that MRD is a powerful predictor of outcome in transplant ineligible patients and is a meaningful therapeutic goal in this patient group. In contrast to conventional CR it retains independent prognostic significance both as a quantitative and qualitative variable. This data further supports the role of MRD as a primary endpoint and surrogate marker for survival in future clinical trials. Figure. Figure. Disclosures Rawstron: Janssen: Research Funding; BD Biosciences: Other: Remuneration; Gilead: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Honoraria; Genzyme: Honoraria; AbbVie: Honoraria; Roche: Honoraria; Celegene: Honoraria. Pawlyn:Celgene: Consultancy, Honoraria, Other: Travel Support; Takeda Oncology: Consultancy. Davies:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Kaiser:Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Takeda: Consultancy; Bristol-Myers Squibb: Consultancy, Other: Travel support; Chugai: Consultancy. Jones:Celgene: Honoraria, Research Funding. Cook:Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Glycomimetics: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. Jenner:Janssen: Consultancy, Honoraria, Other: Travel support, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel support; Takeda: Consultancy, Honoraria, Other: Travel support. Drayson:Abingdon Health: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Jackson:MSD: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau. Morgan:Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Bristol Meyers: Consultancy, Honoraria; Janssen: Research Funding; Univ of AR for Medical Sciences: Employment. Owen:Celgene: Consultancy, Honoraria, Research Funding; Takeda: Honoraria, Other: Travel support; Janssen: Consultancy, Other: Travel support.

Limnological measurements were performed at five or six Missouri reservoirs in June-September 1992–1995 to examine the relation of light conditions and non-algal seston (NAS) to chlorophyll (CHL) and dissolved nutrient concentrations. NAS was estimated as the sum of non-volatile suspended solids and filterable (Whatman 934AH filter) suspended solids. Mean mixed layer irradiance (I mix ) varied ≈20 fold among observations, largely due to variation in light attenuation by NAS. In 42% of the observations, I mix was less than 7 E·m−2 d−1, a range where light limitation is likely. NAS comprised 15–96% (mean= 58%) of total seston and accounted for 89% of the temporal and inter-site variation in I mix . NAS was strongly correlated to total phosphorus (TP) and soluble reactive phosphorus (SRP) concentrations (r= 0.91 and r=0.84, respectively, p 5 mg·L−1 or I mix was < 5 E m−2 d−1, SRP and dissolved inorganic N (DIN) were usually at concentrations capable of saturating algal nutrient u...

(2000). Limnological characteristics of some reservoirs in Thailand. SIL Proceedings, 1922-2010: Vol. 27, No. 4, pp. 2158-2166.

We collected data for five years from the lower Missouri River including discharge (819–10032 m3 s−1), mean depth (2.7–9.3 m), underwater irradiance (0.1–3.7 Ein m−2 d−1), suspended solids (19–2340 mg L−1), total phosphorus (131–1810 μg L−1), total nitrogen (0.9–4.2 mg L−1), nitrate-N (380–3050 μg L−1), silica (8.2–16.8 mg L−1) and chlorophyll (4.5–107 μg L−1). Suspended solids, phosphorus and light attenuation varied directly with discharge. Nitrate, ammonium-N, silica and chlorophyll were strongly seasonal. Chlorophyll was temperature dependent exhibiting winter minima ( 40 μg L−1). In the growing season, chlorophyll co-varied with light and varied inversely with silica and dissolved P. Poor light conditions (mixed depth:photic depth > 10) and rapid flow rates (≈ 150 km d−1) suggest that in situ production of algae is less important than flux of biomass from upstream. Chlorophyll flux and pheophytin increased with discharge indicating contributions of bent...

4-Hydroxymethyl-2,5-diphenyloxazole (4-HOCH2-PPO, 3) was reacted with 3-isocyanatopropyltriethoxysilane (3-ICPS, 4) to form a functionalized silicon alkoxide precursor (3-ICPS-PPO adduct 5). Transparent, colorless, monolithic sol−gel glasses with 3 covalently incorporated at different concentrations were prepared via the copolymerization of tetraethyl orthosilicate (TEOS) and 5 in a H2O/CH3COOH/C2H5OH solution. The gel samples were aged at room temperature, and dried in two stages: first at room temperature, and then at 70 °C, to reduce possible fracture. They have pore diameters in the range 2.2−2.4 nm. By comparison with the simple entrapment procedure, the leaching of scintillator from the sol−gel glass formed as a result of covalent bonding is greatly reduced. Furthermore, these sol−gel glasses are highly efficient at detecting β- radioactivity.

Tritium labelled 2,5-diphenyloxazole ([3H]-PPO, 1) and 4-hydroxymethyl-2,5-diphenyloxazole ([3H]-4-HOCH2-PPO, 2) have been prepared using a one-step metal catalysed isotope exchange procedure. Compound 1 was then encapsulated into a sol–gel glass via the polymerisation of tetraethyl orthosilicate (TEOS). Compound 2 was first reacted with 3-isocyanatopropyltriethoxysilane (3-ICPS) to form a functionalised silicon alkoxide precursor which has a urethane linkage ([3H]-urethane 4), and subsequently copolymerised with TEOS to form covalently bonded sol–gel glasses. The performance of the two glasses was differentiated on the basis of radioactivity leaching tests. In the case of the covalently bound version virtually no leaching occurred, thereby making it an attractive candidate for further applications.

The microwave-enhanced hydrogen–deuterium exchange reaction of a number of nitrogen-containing heterocyclic compounds has been achieved extremely rapidly (

Between April 1993 and November 1994, conductivity, cations, anions and suspended solids were measured at multiple sites in Taechung Reservoir, Korea. The major mechanism regulating ionic composition was dilution by monsoon rain and a resulting interflow current; these forces caused marked spatial and temporal heterogeneity. Ionic dilution was most pronounced in the headwaters during an intense monsoon in 1993 and was accompanied by an increase in the proportion of Na+and Cl−, presumably from rainwater. A decrease of >25% in conductivity and cations occurred during summer 1993 at the plunge-point due to a temperature difference between the lake water and an interflow. In contrast, the 1994 monsoon was weak, ionic dilution was not apparent, and spatial-temporal variation was modest. Overall reservoir salinity was a direct function of water residence time which is regulated by monsoon intensity. Differences in hydrology between years also influenced seston composition; inorganic suspended solids dominated total suspended solids in 1993, but in 1994 the organic fraction was the major component.

The application of microwaves to synthetic organic chemistry is currently experiencing considerable growth. Here we show how the area of radiochemistry, with particular reference to the synthesis of 3H- (or T-), 11C- and 18F-labelled compounds, can benefit. Faster, cleaner, more selective reactions are possible with the formation of much reduced levels of radioactive waste.

Current hypotheses, based on physical and chemical theory, that account for bluegreen-blooms in lakes were evaluated in Taechung Reservoir, Korea, during May 1993–November 1994. Seasonal patterns of chlorophyll (Chl) were similar in 1993 and 1994, but the taxonomic composition and size structure of the phytoplankton communities differed between years. During August–September 1994, bluegreens comprised >80% of total cell numbers and net-Chl (fraction of Chl>35 μm) was 63% of total Chl, whereas in 1993, diatoms (Melosira) were the major taxa, and ultra-Chl ( 25 kg μm−2), high water temperature (>28°C), and reduced silica input. Low N/or N:P ratios and the concentration of monovalent cations (Na+ and K+) were not determining factors in this system, but light and pH seemed to act as secondary factors. Our study suggests that the magnitude and frequency of bluegreen blooms in Asian waterbodies may be reduced during an intense monsoon, but increased during a weak monsoon.

We investigated relationships between sestonic chlorophyll (Chl), total phosphorus (TP), and total nitrogen (TN) at 23 sites on 13 streams in the Missouri Ozarks. There was a strong curvilinear relationship between mean sestonic Chl and both mean TP (R2 = 0.78) and mean TN (R2 = 0.70). Both models were improved when catchment area was included with either TP (R2 = 0.90) or TN (R2 = 0.84). Limited to 17 sites without point source nutrient additions, the relationship between sestonic Chl and both TP and TN was linear. Including catchment area strengthened linear models with either TP (R2 = 0.94) or TN (R2 = 0.84). Land use (percent row crop or percent forest), together with catchment size, was also a good predictor of sestonic Chl in Ozark streams without point sources. When catchment area and TP or TN were used to predict sestonic Chl on specific dates following catastrophic flooding, models were less accurate than those based on long-term averages, but still explained 55-74% of the variance in sestonic Chl. Our results demonstrate that sestonic Chl is closely associated with nutrients and catchment area in Ozark streams and that nutrient - sestonic Chl models may have broad application in running waters.

Keywords: NAIC; data processing; database; modelling; specific activity; isotopic abundance

Tritium ( 3 H) NMR spectra of a number of compounds prepared via metal-catalyzed H/T reduction/ exchange of unsaturated hydrocarbons are presented. These show the considerable benefits that emerge from using a tritium cryo-probe.

You can always count on finding the Mississippi just where you left it last year. But the Missouri is a tawny, restless, brawling flood. It cuts corners, runs around at night, fills itself with snags and traveling sandbars, lunches on levees, and swallows islands and small villages for dessert. Its perpetual dissatisfaction with its bed is the greatest peculiarity of the Missouri.... It makes farming as fascinating as gambling. You never know whether you are going to harvest corn or catfish (Fitch 1907, p. 637).

(1998). Use of a subsurface plankton layer to benefit a cage-culture fishery in Lake Phewa, Nepal. SIL Proceedings, 1922-2010: Vol. 26, No. 5, pp. 2220-2227.

A commercial epoxy prepolymer (MY750) was cured with novel modified imidazole curing agents under both isothermal and dynamic scanning conditions. The thermal behaviour of the formulated mixtures was investigated using differential scanning calorimetry and thermogravimetric analysis, and glass transition temperature (Tg) values derived for polymers resulting from both cure schedules. Tg values and the thermal stability of polymers arising from the isothermal cure schedules were generally higher than those for the corresponding dynamic cure. For samples cured by the dynamic curing process, a lower heating rate resulted in higher Tg values and superior thermal stability. The same findings were obtained for samples cured by the isothermal curing process when the relatively low initial cure temperatures were optimal. The results of this study indicate that the initial and post-cure conditions may affect the final properties, and support the view that both the initial and post-cure schedules are of critical importance in governing the nature of the early network formation and the final network structure.

(1998). An examination of land cover and stream water quality among physiographic provinces of Missouri, U.S.A. SIL Proceedings, 1922-2010: Vol. 26, No. 3, pp. 940-947.

Selby Lake in Gates of the Arctic National Park and Preserve was assessed as oligotrophic due to measurements of low nutrient concentrations and resultant low planktonic biomass as total chlorophyll. An orthograde oxygen profile in early summer also indicated an oligotrophic condition. Total nitrogen averaged about 0.4 μg·L−1 and total phosphorus about 4 μg·L−1, resulting in a TN:TP ratio of about 100, which indicated the planktonic algae were probably limited by phosphorus. Nutrient stimulation bioassays confirmed this. Nitrogen alone was not stimulating to plankton algal growth, but nitrogen and phosphorus added together in the bioassays stimulated growth more than just phosphorus, as is often found in oligotrophic lakes. Aerial observation of Selby Lake and similar nearby lakes had indicated that epilithic benthic algal biomass was probably relatively high because the extensive shallows were visibly green. When recent growth in the ice-scour zone (< 2 m) was sampled in early July, the whole la...

The goals of the Lakes of Missouri Volunteer Program are to involve citizens in the collection of water samples to monitor lake trophic state and to provide outreach education about lake water quality. Results indicate data generated with volunteer help are of the same quality as that generated by a research laboratory. This conclusion is based on three different methods of evaluation: (1) Comparisons of volunteer and University collected samples showed trophic state classifications were the same for 74% of lakes based on total phosphorus, 84% for total nitrogen and 89% for chlorophyll; (2) Agreement between paired chlorophyll filters was assessed to gauge volunteer processing technique; 88% of the filter pairs was considered good or excellent based on a rating scale developed for this program; (3) Split sampling showed no significant differences for total suspended solids, chlorophyll or total nitrogen. Total phosphorus analysis showed a significant difference with volunteer samples being consis...

To simulate the results of surface treatments, commonly encountered functional groups were introduced onto the surface of the carbon fibre model. The carbon fibre model used in this study is based on the single layer diagonal graphitic plane, comprising 52 six-membered rings, in a 4×13 configuration, and of 150 carbon atoms. Surface treatment was represented by the introduction of functional groups (–R): each time, a C–C bond was broken along the edge of the plane, and a pair of –R groups was added to the graphitic plane. The total number of functional groups (n) was six. The effect of these functional groups on the non-covalent bonding interactions at the composite interface between carbon fibre and epoxy resin was investigated using a previously established BLENDS method. The compatibility of the resin and fibre in this model, indicated by the interaction parameter χ(T ), was dependent upon two factors: steric bulk and electrostatic interactions. The halogen substituents show a decrease in χ(T ), as one descends the group. Maximum interaction tends to be a function of steric bulk and polarizability in this group. The alkyl (CnH2n+1) and phenyl substituents also show a decreasing trend inχ(T ) with increasing size, although the interaction parameter with methyl is anomalously low in all cases.

Transparent, colourless, monolithic sol-gel glasses doped with 2,5-diphenyloxazole (PPO) at different concentrations were prepared via the polymerisation of tetraethyl orthosilicate (TEOS) in a H 2 O-AcOH-EtOH-PPO solution. The gel samples were aged at room temperature, and dried in two stages: first at room temperature, then at 70°C to reduce possible fracture. They have pore diameters in the range 1.8-2.1 nm. The leaching of PPO from the sol-gel glass was monitored using ultraviolet (UV) and X-ray photoelectron spectroscopy (XPS). The results show that the sol-gel glasses dried at the higher temperature leach less than those dried at room temperature. These sol-gel glasses, either in monolith or powder form, are effective in detecting β – radioactivity.

Limnological data were collected over a two-year period from 12 lakes in the Missouri River floodplain in order to evaluate lake trophic status and the influence of basin type and connectivity on nutrient, seston, and phytoplankton dynamics. The lakes were located in west-central Missouri and included eight scour basins formed by levee breaks during a 1993 flood and four older oxbow lakes. The Missouri River was also sampled. Five of the scour basins (connected scours) were inundated by the Missouri River for varying periods during the study. The other lakes (protected lakes) were hydrologically isolated from the river by levees. On the basis of mean total phosphorus (TP-61-282 μg/L), mean total nitrogen (TN-0.7-2.1 mg/L), mean chlorophyll (CHL-22-67 μg/L), and mean suspended solids (TSS-16-93 mg/L), all 12 sites were highly eutrophic compared to other lakes in Missouri. Nutrient fractions and seston composition indicated dominance of inorganic nutrients and abiotic seston in the riverine lakes. Maximum concentrations of nutrients and TSS occurred in oxbow lakes during periods of sediment resuspension and in connected scours during floods in spring 1995 and 1996 when connected sites were inundated by the Missouri River. Algal blooms with peak CHL>200 μg/L occurred sporadically in the oxbow lakes. Similarly large blooms (peak CHL 81–689 μg/L) occurred in connected scours when low river levels reduced exchange with the river. Reduced connectivity was accompanied by rapid loss of dissolved N and P fractions, especially nitrate. Protected scours had lower average TP, TN, and TSS than the other sites and were less temporally variable.

A non-destructive tritium–hydrogen exchange procedure has been developed in order to determine the concentration of exchangeable hydrogens on surfaces, and in this particular instance it has been used on carbon fibres. The results show that the concentrations of ‘active sites’ on the surfaces of Courtaulds Grafil XAS and XAU carbon fibres are 2.61 and 0.08 μmol g−1 respectively. When the XAS fibres are subjected to a standard methylation procedure the concentration of exchangeable hydrogens is reduced to 0.79 μmol g−1.On the other hand, when XAU fibres are subjected to oxidation in concentrated nitric acid, the concentration of exchangeable hydrogens is increased to 10.27 μmol g−1.

Molecular simulation was used to calculate the physico-mechanical properties of a linear epoxy system. Values of glass transition temperature ( T g ) compare well with experiments as did elastic moduli. A correlation between hydrogen-bonding energy and T g was derived indicating the importance of hydrogen-bonding in this system.

We report a study of the curing mechanism of 13C labelled bisphenol A dicyanate ester in the presence of a electrolytically surface treated XAS carbon fibre using several techniques — solid state 13C NMR, scanning electron microscopy (SEM) and diffuse reflectance FTIR. Comparison of the results obtained in pure matrices and solution shows that the resin undergoes the same reaction mechanism in both cases and forms the sym-triazine network structure in the composite.

Two carbon fibre models, based on microscopic and XPS evidence of electrochemical surface treatment, have been proposed. A diagonal graphitic plane, comprising 52 six-membered rings (in a 4×13 configuration) and of 150 carbon atoms, was built as the principal, non-surface-treated carbon fibre model. Three layers of graphitic planes, each comprising 117 six-membered rings (in a 9×13 configuration) and of 300 carbon atoms, formed the multi-layer graphitic model. The nature and level of surface treatment was represented by the introduction of hydroxy (OH) and carboxy (COOH) groups: each time, a C–C bond was broken along the edge of the plane, and a pair of OH and COOH groups was added to the graphitic plane. Six pairs of OH and COOH were introduced gradually. The functional groups were distributed evenly along the edge of each graphitic plane. Their non-covalent bonding interaction with various amine-cured epoxy polymer models was simulated using the Cerius 2 BLENDS method. Δ mix G was used to indicate the interaction, and hence the interfacial adhesion. The results show a trend, in relation to the level of surface treatment, in agreement with experimental data of composite interlaminar shear strength (ILSS).

A method to correct for irregular, non stationary respiratory motion is required to improve quantitative and qualitative accuracy of Nuclear Medicine Images. Solutions to date rely on temporally regular respiratory motion with static models learnt from training data. An adaptive approach with dynamic parameter learning of motion models is required. To this avail we cast respiratory motion estimation as a Hidden Markov model. An expectation maximization based Kalman smoother algorithm is utilized to infer hidden states of motion from observations of the patient's chest motion alone. The framework is validated using a computational anthropomorphic phantom (XCAT) with seven respiratory cycles with varying amplitude and frequency. A PET study is simulated with four 16mm lung lesions to assess the effectiveness of the approach. Preliminary tests are also performed on dynamic MRI data of a single volunteer. The likelihood of dynamical model fitting is monitored for individual respiratory cycles. Optimal estimates of previously unseen motion are made using the Kalman smoother. The proposed method can correct for respiratory motion to the order of 1.5mm. A thirty percent increase in mean uptake value for the corrected tumors in the simulated PET study was observed.

A framework to facilitate the realization of dynamic MRI data with simultaneously increased temporal and spatial resolution is proposed. Deformable registration to a reference frame of spatially sparse, high temporally resolved two dimensional sagittal slices acquired sequentially across a volunteers lateral dimension serve as a subset of incomplete observation of full three dimensional vector fields. Registration of an averaged, re-binned, single respiratory cycle with full spatial sampling serves as a basis for estimation of full three dimensional vector fields derived from the sparse subset. The inverse of the estimated full 3D vector fields from sparse measurements allows propagation of a high resolution, re binned static volume with breathing modes derived from the sparse dynamic data. Proof of concept experiments are undertaken with the anthropomorphic XCAT phantom. A quantitative evaluation of full vector fields derived from sparse samples in comparison to their ground truth results in a mean error of the order of 1mm. A qualitative assessment of the motion of a propagated high resolution static MRI volume is presented.

In external beam radiotherapy, patient misalignment during set-up and motion during treatment may result in lost dose to target tissue and increased dose to normal tissues, reducing therapeutic benefit. The most common method for initial patient setup uses room mounted lasers and surface marks on the skin. We propose to use the Microsoft Kinect which can capture a complete patient skin surface representing a multiplicity of 3D points in a fast reproducible, marker-less manner. Our first experiments quantitatively assess the technical performance of Kinect technology using a planar test object and a precision motion platform to compare the performance of Kinect for Xbox and Kinect for Windows. Further experiments were undertaken to investigate the likely performance of using the Kinect during treatment to detect respiratory motion, both in supine and prone positions. The Windows version of the Kinect produces superior performance of less than 2mm mean error at 80-100 cm distance. © 2013 IEEE.

Two commercial epoxy resins, MY750 and MY720, were cured over a range of cure temperatures with a series of novel curing agents based on modified imidazoles. A combination of techniques, including dynamic viscometry, proton nuclear magnetic resonance spectroscopy, differential scanning calorimetry, high performance and gel permeation chromatography, were used to analyse the reaction mixture. It appears that for a given formulation and given resin, the viscosity behaviour near gelation is different for different cure temperatures and the mechanism appears to be dependent not only on the nature of the imidazole curing agent, but also on the cure temperature. Higher temperature cure appears to lead to the formation of a less ‘homogeneous’ reaction mixture at the gel point, containing oligomeric chain lengths of higher polydispersity, whereas in the lower temperature cure, oligomers of a smaller range of chain lengths are present.

Carbon fibre pre-impregnated tape (prepreg) was prepared from a range of prepolymers comprising blends of propenyl-functionalized cyanate ester (CE) oligomers with commercial bis-maleimide (BMI) monomers. Cured neat resin plaques and carbon fibre composites were prepared by autoclave moulding. Various blends of a commercial BMI mixture, a CE and a co-monomer with either allyl or propenyl and cyanate pendant groups were prepared. Differential scanning calorimetry (d.s.c.) data were used to monitor cure of neat resin, while dynamic mechanical thermal analysis (d.m.t.a.) was used to assess cure cycles of composite materials by the measurement of glass transition temperatures (Tg). Composite properties measured were interlaminar shear strength, flexural strength, compressive strength and Mode 1 Fracture toughness (GIC).

Zooplankton abundance and biomass were measured in natural lakes and impoundments in Iowa, Kansas, Missouri, and Oklahoma during summer. Zooplankton exhibited wide ranges of abundance (70,000-1,000,000 individuals/m3) and biomass (45–1,000 mg/m3). Communities were dominated by rotifers; they comprised 70% or more of the zooplankton abundance in 41 lakes and, on average, comprised 53% of zooplankton biomass. Zooplankton in Missouri were significantly smaller than those collected in me other states, suggesting predation and regulation of size structure by zooplanktivorous fish may have differed among states at the time of this study. Within the data set, neither the microzooplankton nor the component groups of the macrozooplankton showed consistent changes witii lake trophy. Among die Missouri reservoirs, Daphnia sp. decreased and Diaphanosoma sp. increased in relation to algal chlorophyll. Both zooplankton abundance and biomass were positively correlated with algal chlorophyll (r=0.30–0.58). This ...

Cherry Creek Lake in Colorado is a shallow flood control reservoir mat exhibits infrequent blooms of nitrogen-fixing cyanobacteria one of which occurred in summer 1992. In nutrient addition experiments run before and during the bloom, added nitrogen significantly stimulated algal growth. The magnitude of the N-effect was much greater in the pre-bloom experiments in which added phosphorus had no effect. During the bloom, added P had small but significant effects on growth indicating concurrent P and N limitation. Monitoring data suggest that phytoplankton is usually N-limited in the lake, but, for unknown reasons, blooms of N-fixing algae are rare.

A tritium labelled phospholipase A 2 (PLA 2 ) amide analogue inhibitor was prepared by the reduction of an alkene precursor. Diimide, heterogeneous and homogeneous metal catalyzed reduction methods were assessed for their suitability for the preparation of a tritiated ligand for 3 H NMR spectroscopic studies. The chosen homogeneous metal-catalyzed method gave a product of specific activity 57 Ci mmol -1 , which was isolated by flash chromatography. The binding of this tritiated substrate to bovine pancreatic PLA 2 was observed by 3 H NMR spectroscopy in the presence of calcium ions. Chemical shift changes suggest that the tritium atoms are located within the hydrophobic pocket of the protein, close to two phenylalanine residues

The preparation of metal-aromatic diamine complexes is reported along with their characterisation by infrared spectroscopy. Dynamic viscometry (gel-point determination) was used to assess the reactivity of some of the metal-diamine complexes with a commercial epoxy resin. Significant differences were observed in the viscosity profiles for formulations with different metal contents. These related to the reactivities of the diamines which are themselves a function of metal content.

The development of radio-size-exclusion chromatography and its application to two widely different areas, (a) the determination of the radiochemical purity of 3H- and 14C-labelled biopolymers and (b) the kinetics of epoxy resin formation, is reported. The versatility of the instrument is also reflected in the fact that it is able to function in one of four modes, i.e. HPLC, radio-HPLC, SEC and radio-SEC.

Regression analysis of a data set compiled from the literature (n = 292) showed that summer mean chlorophyll concentration (Chl) among temperate streams bore a strong (R 2 = 0.67) curvilinear relationship with summer mean total phosphorus concentration (TP). The predicted slope of the TP-Chl relationship (Chl:TP) ranged between 0.22 at TP = 50 mg·m -3 and 0.08 at TP = 1030 mg·m -3 , the highest value of TP in our data set. A bivariate model indicated that stream catchment area had a significant effect on Chl at all levels of TP and predicted a 2.3-fold increase in Chl:TP as the stream catchment area increased from 100 to 100 000 km 2 . We suggest that TP may provide a reliable basis for predicting Chl in small and large temperate streams worldwide.

A wide range of aromatic compounds containing suitable directing groups can be labelled efficiently with deuterium using isotopic exchange catalysed by an easily prepared polystyrene based ortho-exchange catalyst. The labelling reactions can be carried out efficiently at ambient temperature by simple stirring of the substrate and catalyst under a deuterium atmosphere for a few hours. Isolation consists of a simple filtration and evaporation of the solvent. Deuterium is incorporated with ortho-regiospecificity.

Suspended sediment, nutrients and algal chlorophyll (CHL) were monitored over a 29 month period at 19 sites in Mark Twain Lake, a 7550 ha reservoir in northeastern Missouri. Sampling began during a record drought and continued through subsequent periods of average rainfall. Turbid inflows (1000 mg/L TSS) during flood events produced consistently high concentrations of suspended sediment (>200mg/L) and nutrients (TP >300 μg/L, TN >2mg/L) in headwater areas, but effects in the reservoir mainstem varied with thermal regime. Inflows during winter mixing affected the entire waterbody while inflows during stratified periods had little effect on surface strata in the mainstem. Loading of nutrients and sediment to the trophogenic zone thus depended less on quantity of inputs than their timing. The size range of suspended materials initially declined with increasing hydraulic residence time but subsequently increased as organic, presumably, autochthonous seston replaced allochthonous minerals as the dominant particle type. Algal blooms seemed to increase sedimentary loss of mineral seston from the epilimnion. Dynamics of phosphorus and suspended sediment were closely parallel and dominated by fluvial inputs. Dynamics of TN, organic N, nitrate and ammonia, however, seemed equally affected by external inputs and internal cycling and TN exhibited far less year to year variation than TSS or TP. CHL time series revealed numerous brief blooms with little temporal or spatial consistency. Phytoplankton may have become nutrient limited during blooms but were probably light limited except during clear water periods near the start and end of the study. On the basis of growth experiments and maximum areal CHL, algal biomass was probably light limited at irradiances (2-5 Em -2 d -1 , a range comprising 79 % of our observations. The strong relation between phosphorus and suspended material in Mark Twain Lake holds for other Missouri reservoirs and results in a dome-shaped CHL-TP relation in which phytoplankton are P-limited at low TP (low turbidity) and light limited at high TP (high turbidity). This trend is less evident among Iowa lakes and is probably regio-specific.

Daphnia lumholtzi, a large cladoceran native to Africa, Asia, and Australia, has recently invaded reservoirs of the southern United States. We examined its distribution, history of invasion, and population dynamics in Missouri reservoirs. Surveys detected the species in 7 of 112 reservoirs in 1992 and 11 of 119 reservoirs in 1993. Analysis of quantitative zooplankton samples from two reservoirs over a 7-year period indicated that D. lumholtzi first reached detectable densities in 1990 and persisted during 1991–1993. Population maxima typically occurred in late summer, with the species absent from the plankton during winter and spring. Based on its current distributional patterns, D. lumholtzi appears to be capable of colonizing most reservoirs in the southern regions of North America.

Effects of crude oil on survival and behavior of the mayfly Hexagenia bilineata were evaluated in laboratory studies. Mayfly nymphs were exposed to the water soluble and oil residue fractions of crude oil. Mayfly survival was not reduced by a 96-h exposure to either the water soluble fraction or the oil residue mixed with sediment. However, significant mortality did result from a 21-day exposure to oil residue mixed with sediment at concentrations as low as 500 microg g(-1). Survival was also reduced after a 21-day exposure to oil-contaminated sediments (1905 microg g(-1)) collected 6 weeks after a crude oil spill in the Chariton River, Missouri. In a behavioral test measuring habitat exclusion, organisms did not avoid contact with sediment containing oil residue (50-800 microg g(-1)). Collectively, results from these studies indicate that exposure to oil residue in sediment will reduce survival of H. bilineata in the laboratory and may reduce survival in the environment for 6 weeks or more after an oil spill.

The reaction between phenyglycidyl ether and a series of primary aromatic amines has been studied under conditions where [epoxide][amines](conditions which we categorise as ideal) using a radio-high-performance liquid chromatography (HPLC) method that is shown to be very versatile and capable of wide application. The results show that the small amounts of water present in the reaction medium possess a catalytic role as do the hydroxylated species formed during the course of the reaction. The detailed information so obtained makes it possible to use numerical techniques so that a comparison can be made between a theoretical model and the actual experimental behaviour.

Respiratory motion correction degrades quantitatively and qualitatively Nuclear Medicine images. We propose that adaptive approaches are required to correct for the irregular breathing patterns often encountered in the clinical setting, which can be addressed within a Bayesian tracking formulation. This allows inference of the hidden organ configurations using only knowledge of an external observation such as a parametrized external surface. The flexible framework described provides a method to correct for organ motion whilst accommodating for irregular unseen respiratory patterns. In this work we utilize a Kalman filter and compare it with a Particle filter. A novel adaptive state transition model is also introduced to describe the evolution of organ configurations. The Kalman filter marginally outperforms the Particle filter, both approaches however offer an effective motion correction mechanism, correcting for motion with errors of around 1-3mm. We present results of simulated PET images derived from XCAT to demonstrate the efficacy of the approach. © 2012 IEEE.

Copolymers containing diethylsiloxane and functional siloxane groups of the form RR′SiO (where R, R′=phenyl, and R=methyl, R′=3,3,3-trifluoropropyl) were synthesized by equilibrium polymerization of the appropriate cyclotrisiloxanes in the presence of KOH. Quantitative 29 Si n.m.r. spectroscopy indicated that the copolymers possessed random microstructures. D.s.c. and dynamic mechanical analysis show that both substituents are effective in lowering the crystal melting and low-temperature crystal-crystal transitions with respect to the diethylsiloxane homopolymer, and ultimately lead to non-crystalline copolymers.

Copolymers containing diethylsiloxane and functional siloxane groups of the form RR′SiO (where R=phenyl, and R′=ethyl or methyl) were synthesized by equilibrium polymerization of the appropriate cyclotrisiloxanes in the presence of KOH. Quantitative 29Si n.m.r. spectroscopy indicated that the copolymers possessed random microstructures. Differential scanning calorimetry (d.s.c.) analysis showed that both substituents are effective in lowering the crystal melting and low-temperature crystal-crystal transitions with respect to the diethylsiloxane homopolymer, and ultimately lead to non-crystalline copolymers.

Introduction Multiple myeloma (MM) is characterised by the malignant expansion of clonal plasma cells in the bone marrow (BM). We and others have used massive parallel sequencing to describe the somatic aberrations acquired in different subclones in newly diagnosed MM (NDMM). These studies have showed that chemotherapy has an impact on intra-clonal heterogeneity, but more analyses are required in paired presentation/relapse samples and samples from multiple sites at the same and different time points. Materials and methods We have studied 49 paired presentation/relapse patients from a series of 463 NDMM patients entered into the Myeloma XI trial (NCT01554852). To understand the impact of spatial separation within the MM clone and the consideration that MM is a metastatic disease, we examined BM aspirates and compared them to targeted biopsies from extramedullary disease sites in 9 MM patients. These cases were 1 patient with samples bilaterally collected from the hip during the course of the disease, 4 MM cases with plasma cell leukemia (PCL), 3 MM cases with plasmacytomas, 1 MM patient with ascites, and 1 MM case with pleural effusion. DNA from both BM and peripheral blood samples were used for whole exome sequencing plus a pull down of the MYC, IGH, IGL and IGK loci following the SureSelect Target Enrichment System for Illumina Paired-End Sequencing Library v1.5. Exome reads were used to call single nucleotide variants, indels, translocations, and copy number aberrations. Mean sequencing depth was 59.3x. The proportion of mutant tumor cells carrying a mutation was inferred. The presence and proportion of subclones will be defined using bioinformatics tools. Results For the 463 NDMM samples, the following 15 significantly mutated genes are seen KRAS (n=103 mutations), NRAS (n=88), LTB (n=53), DIS3 (n=49), BRAF (n=37), EGR1 (n=22), FAM46C (n=20), IRF4 (n=19), TRAF3 (n=17), HIST1H1E (n=16), TP53 and FGFR3 (n=14), CYLD (n=13), MAX (n=12), and RB1 (n=5). These mutations were seen within all clonal cells and at subclonal levels, consistent with the mutations being acquired at different time points and being associated with different subclonal fitness. We show that NDMM have a mean number of exonic mutations of 61.1±13.0, in contrast to samples taken at the time of relapse, which show an average of 80.6±25.4, Figure 1A. We report diverse patterns of subclonal evolution: no change, subclonal tiding, and subclonal tiding with new subclones arising. We are currently examining samples taken during clinical remission to track subclones at the time of response. For patient with multiple samples taken at different timepoints, 77 mutations were shared across all samples but, of note, specific mutations were seen at the same timepoint in different sites (13/1662 R2R vs 13/1662 R2L), which illustrates the impact of sampling differences in reporting mutation calls and differential response to therapy, Figure 1B. This is also observed in a plasmacytoma case with both a BM aspirate sample containing 11 mutations (including NRAS c.183A>T and BRAF c.1783T>C), and a femur plasmacytoma with 18 mutations, of which only 2 are shared with the BM sample, Figure 3. One of these shared lesions is BRAF c.1783T>C, the cancer clonal fraction of which increases ten-fold, suggesting that the sub-clone with this mutation disseminated from the BM and founded the plasmacytoma. Conclusion Our preliminary data demonstrate that MM subclones not only respond differently to clinical treatment, but also have different biological properties leading to cause extramedullary disease. To our knowledge, this is the first comprehensive genetic analysis of the spatio-temporal heterogeneity in myeloma and reveals genetic differences due to sampling bias. Figure 1. (A) Number of mutations in MM patients at clinical presentation and relapse. Each patient sample is represented by a dot. Lines and error bars correspond to the average and the standard error of the mean values, respectively. Difference was not statistically significant (p >0.05, t-test). (B) MM patient analysed at presentation and following two relapses (top). The number of mutations increases through disease (bottom, left panel). Venn plot shows the number of shared and specific mutations for each time point (bottom, right panel). (C) Case with a MM sample (green) and a femur plasmacytoma (blue). Venn plot shows shared and specific mutations to the bone marrow or the plasmacytoma site. Figure 1. (A) Number of mutations in MM patients at clinical presentation and relapse. Each patient sample is represented by a dot. Lines and error bars correspond to the average and the standard error of the mean values, respectively. Difference was not statistically significant (p >0.05, t-test). (B) MM patient analysed at presentation and following two relapses (top). The number of mutations increases through disease (bottom, left panel). Venn plot shows the number of shared and specific mutations for each time point (bottom, right panel). (C) Case with a MM sample (green) and a femur plasmacytoma (blue). Venn plot shows shared and specific mutations to the bone marrow or the plasmacytoma site. Disclosures Jones: Celgene: Other: Travel support, Research Funding. Peterson:University of Arkansas for Medical Sciences: Employment. Brioli:Celgene: Honoraria; Janssen: Honoraria. Pawlyn:Celgene: Honoraria, Other: Travel support; The Institute of Cancer Research: Employment. Gregory:Janssen: Honoraria; Celgene: Honoraria. Davies:Onyx-Amgen: Membership on an entity's Board of Directors or advisory committees; Array-Biopharma: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda-Millennium: Membership on an entity's Board of Directors or advisory committees; University of Arkansas for Medical Sciences: Employment. Morgan:CancerNet: Honoraria; University of Arkansas for Medical Sciences: Employment; MMRF: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Weisman Institute: Honoraria; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda-Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Introduction Hyperdiploidy (HRD) comprises the largest pathogenetic subgroup of myeloma. However, its clinical and molecular characterisation is incomplete. Here, we investigate HRD using a novel high-throughput molecular analysis method (MyMaP - Myeloma MLPA and translocation PCR; Kaiser MF et al., Leukemia 2013; Boyle EM et al., Gen Chrom Canc 2015) in a large cohort of 1,036 patients from the UK NCRI Myeloma XI trial. Materials, Methods and Patients Copy number changes, including gain of chromosomes 5, 9 and 15, as well as translocation status were assayed for 1,036 patients enrolled in the UK NCRI Myeloma XI (NCT01554852) trial using CD138+ selected bone marrow myeloma cells taken at diagnosis. HRD was defined by triploidy of at least 2 of analysed chromosomes 5, 9 or 15. Analysis was performed on standard laboratory equipment with MyMaP, a combination of TC-classification based multiplex qRT-PCR and multiplex ligation-dependent probe amplification (MLPA; MRC Holland). The parallel assessment of multiple loci with copy number alteration (CNA) by MLPA allowed unbiased association studies using a Bayesian approach. Semi-quantitative gene expression data for CCND1 and CCND2 was generated as part of the multiplexed qRT-PCR analysis. Median follow up for the analysis was 24 months. Results Of the 1,036 analysed patients, 475 (46%) were HRD. Of these, 325 (68%) had gain(11q25), 141 (29.7%) gain(1q), 43 (9.1%) del(1p32) and 36 (7.5%) del(17p). Gain(11q25) was significantly associated with HRD (Bayes Factor BF01 HRD cases were classified as D1, D2 or D1+D2 according to the TC classification based on qPCR CCND1 and CCND2 expression values and expression was correlated with copy number status. An association of the D1 subtype with gain(11q25) and of D2 with gain(1q) was confirmed. CCND1 expression was significantly (P HRD was associated with favourable outcome when compared to non-HRD cases with median PFS 28.8 vs. 21.7 months (P Within HRD cases, gain(1q) was associated with shorter PFS (P =0.02) and OS (P =0.009), associating the D2 group with inferior outcome. Presence of del(1p32) was associated with inferior PFS (P =0.01) and OS (P =0.0007) in the HRD subgroup and del(17p) was associated with inferior OS (P =0.04) with a trend for PFS. HRD cases with presence of any of the risk factors gain(1q), del(1p32) or del(17p) in comparison to those without had a median PFS of 25.1 vs 35.1 months (P =0.0001) and 24-month OS of 73.8% vs 89.0% (P Conclusion We describe in a large trial cohort an association between gain(11q25) and the D1 hyperdiploid subtype as well as gain(1q) and the D2 subtype, a finding that has so far only been inferred by gene expression array data in the original TC classification. We also find an association with adverse outcome for the D2/gain(1q) subtype. Our findings demonstrate that the novel molecular approach MyMaP allows precise molecular sub-classification of HRD myeloma. Disclosures Kaiser: BristolMyerSquibb: Consultancy; Chugai: Consultancy; Janssen: Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding. Pawlyn:Celgene: Honoraria, Other: Travel support; The Institute of Cancer Research: Employment. Jones:Celgene: Other: Travel support, Research Funding. Savola:MRC Holland: Employment. Owen:Celgene: Honoraria, Research Funding; Janssen: Honoraria. Cook:Takeda Oncology: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; BMS: Consultancy; Celgene: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau. Gregory:Janssen: Honoraria; Celgene: Honoraria. Davies:Onyx-Amgen: Honoraria; Celgene: Honoraria; University of Arkansas for Medical Sciences: Employment; Takeda-Milenium: Honoraria. Jackson:Amgen: Honoraria; Takeda: Honoraria; Celgene: Honoraria. Morgan:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Weisman Institute: Honoraria; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda-Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; University of Arkansas for Medical Sciences: Employment; CancerNet: Honoraria; MMRF: Honoraria.