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The circadian clock provides a mechanism for anticipating environmental cycles and is synchronized by temporal cues such as daily light/dark cycle or photoperiod. However, the Arctic environment is characterized by several months of Midnight Sun when the sun is continuously above the horizon and where sea ice further attenuates photoperiod. To test if the oscillations of circadian clock genes remain in synchrony with subtle environmental changes, we sampled the copepod Calanus finmarchicus, a key zooplankter in the north Atlantic, to determine in situ daily circadian clock gene expression near the summer solstice at a southern (74.5° N) sea ice-free and a northern (82.5° N) sea ice-covered station. Results revealed significant oscillation of genes at both stations, indicating the persistence of the clock at this time. While copepods from the southern station showed oscillations in the daily range, those from the northern station exhibited an increase in ultradian oscillations. We suggest that in C. finmarchicus, even small daily changes of solar altitude seem to be sufficient to entrain the circadian clock and propose that at very high latitudes, in under-ice ecosystems, tidal cues may be used as an additional entrainment cue.

This is the first report of the combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) with Rituximab (GEM-PR) for diffuse large B-cell lymphoma (DLBCL). Thirty-nine patients with relapsed or refractory DLBCL in this study received GEM-P with (n = 24) or without Rituximab (n = 15) 64% patients had Stage III/IV disease. The overall response rate (ORR) was 59% (95% CI 42.1-74.4); 11/39 (28%) patients attained complete response. Patients received a median of two cycles (1-4) of treatment. For GEM-PR group, the ORR was 67% (95% CI 45-84%) compared to 47% (95% CI 21-73%) in GEM-P alone. one-year progression-free survival was 51% (95% CI 28-69%) in GEM-PR group compared to 27% (95% CI 8-49%) in GEM-P alone (P = 0.04). GEM-P is an effective second-line regimen in patients with relapsed or refractory DLBCL and the addition of Rituximab appears to further improve outcomes.

Researchers working on environmentally relevant organisms, populations, and communities are increasingly turning to the application of OMICS technologies to answer fundamental questions about the natural world, how it changes over time, and how it is influenced by anthropogenic factors. In doing so, the need to capture meta-data that accurately describes the biological "source" material used in such experiments is growing in importance. Here, we provide an overview of the formation of the "Env" community of environmental OMICS researchers and its efforts at considering the meta-data capture needs of those working in environmental OMICS. Specifically, we discuss the development to date of the Env specification, an informal specification including descriptors related to geographic location, environment, organism relationship, and phenotype. We then describe its application to the description of environmental transcriptomic experiments and how we have used it to extend the Minimum Information About a Microarray Experiment (MIAME) data standard to create a domain-specific extension that we have termed MIAME/Env. Finally, we make an open call to the community for participation in the Env Community and its future activities.

The light regime is an ecologically important factor in pelagic habitats, influencing a range of biological processes. However, the availability and importance of light to these processes in high Arctic zooplankton communities during periods of 'complete' darkness (polar night) are poorly studied. Here we characterized the ambient light regime throughout the diel cycle during the high Arctic polar night, and ask whether visual systems of Arctic zooplankton can detect the low levels of irradiance available at this time. To this end, light measurements with a purpose-built irradiance sensor and coupled all-sky digital photographs were used to characterize diel skylight irradiance patterns over 24 hours at 79°N in January 2014 and 2015. Subsequent skylight spectral irradiance and in-water optical property measurements were used to model the underwater light field as a function of depth, which was then weighted by the electrophysiologically determined visual spectral sensitivity of a dominant high Arctic zooplankter, Thysanoessa inermis. Irradiance in air ranged between 1–1.5 x 10-5 μmol photons m-2 s-1 (400–700 nm) in clear weather conditions at noon and with the moon below the horizon, hence values reflect only solar illumination. Radiative transfer modelling generated underwater light fields with peak transmission at blue-green wavelengths, with a 465 nm transmission maximum in shallow water shifting to 485 nm with depth. To the eye of a zooplankter, light from the surface to 75 m exhibits a maximum at 485 nm, with longer wavelengths (>600 nm) being of little visual significance. Our data are the first quantitative characterisation, including absolute intensities, spectral composition and photoperiod of biologically relevant solar ambient light in the high Arctic during the polar night, and indicate that some species of Arctic zooplankton are able to detect and utilize ambient light down to 20–30m depth during the Arctic polar night. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Abstract 2921 Poster Board II-897 Background: Despite improvements in outcome of patients (pts.) with DLBCL, the prognosis for those who relapse after first-line treatment remains very poor. This retrospective analysis reports outcome of pts. with DLBCL treated before the routine use of Rituximab, with a median (med.) follow-up of 12 years. Patients and Methods: Between 1985 and 2003, 461 pts. were diagnosed with DLBCL at SBH. 384/461 (83%, male: 208, med. age: 60 years, range 17-95) were treated with curative intent (CI) and form the basis of this analysis. Those with primary CNS or primary mediastinal B-cell lymphoma and HIV +ve pts. were excluded. Histology at diagnosis included 31 pts. with ‘composite' lymphoma (29 follicular [FL], 1 lymphoplasmacytic, 1 ‘MALT') and 17 with ‘discordant' lymphoma (all FL).The majority, 142 (37%), had Stage IV disease, 99 (26%) stage I, 88 (23%) stage II and 55 (14%) stage III. The IPI score (ascribed retrospectively) was low-risk in 189 (49%), low-intermediate (int.) in 110 (29%), high-int. in 64 (17%) and high-risk in 21 (5%). 354/384 (92%) received an anthracycline-containing regimen, according to protocols in use at the time. 30 pts. (8%) with localised disease received radiotherapy alone. Prior to 2001, all pts. received prophylactic intra-thecal methotrexate; subsequently, only those at high risk for CNS relapse did so. Results: CR/CRu was achieved in 240/384 pts. (63%) and PR in 67 (17%). 53 (14%) did not respond (NR) and 24 (6%) died of causes related to initial therapy. Overall survival (OS) correlated with outcome to therapy (CR/CRu vs PR vs NR, p Conclusion: Despite the curative potential of HDT, these data confirm that recurrence of DLBCL, in an unselected patient population, carries an appalling prognosis. Improving initial therapy is therefore crucial. In pts. in whom conventional 2nd-line therapy has failed, it is entirely justifiable to evaluate experimental therapies. Disclosures: No relevant conflicts of interest to declare.

There is currently no standard salvage chemotherapy regimen in patients with relapsed/ refractory DLBCL. We have previously shown that GEM-P is an effective salvage regimen in patients with relapsed/refractory lymphoma; 10 patients in this study had DLBCL (Br J Cancer2005;92:1352–7). The aim of this study was to evaluate the combination of GEM-P in a larger subset of DLBCL patients. This has not been reported before. Between 1/01 and 3/05, 39 (10 patients had transformed lymphoma) heavily pre-treated relapsed and refractory DLBCL patients received GEM-P; 24 (61%) of these patients also received Rituximab (R). The median age was 49 y (range, 18–68); 28 males; 64% patients had Stage III/IV disease; 69% had IPI ≥2. The median time from diagnosis to start of GEM-P ± R was 17 mo (range, 2mo-7 yrs). All patients had previously received an anthracycline-based regimen. The disease status at start of GEM-P ± R was: 24 patients were in 1st relapse, 7 had primary refractory disease, 5 were in 2nd relapse and 3 in 3rd relapse. Median number of cycles of GEM-P ± R received were 2 (range, 1–4). The overall response rate (RR) was 59% (95% CI 42.1–74.4). 11 (28%) patients attained complete response, 12 partial response and 15 patients did not respond; 1 patient died of progressive disease. The median response duration to GEM-P ± R in 23 responding patients was 332 days (range, 36–1530) compared to 170 days (range, 26–2264) in 32 responding patients to 1st-line chemotherapy. Of the 24 patients who received R (not randomised; given when available via NHS funding network) with GEM-P, the overall RR was 67% (95% CI 45–84) compared to 47% (95% CI 21–73) in those who did not receive R (P=0.2). Eight patients were consolidated with high-dose therapy which was an autologous stem cell transplant (ASCT) in 7 (all are alive and well except one who relapsed 4 mo later and died of progressive disease) and a reduced intensity conditioning matched unrelated donor transplant in 1 patient who died of transplant-related complications. The remaining patients did not undergo an ASCT due to treatment failure (n=16), cardiac insufficiency (n=2) and subclavian vein thrombosis (n=1). ASCT was not planned in the other 12 patients because of indolent histology (n=2), inadequate stem cell collection (n=1), lost-to follow-up (n=1), previous high-dose therapy (n=3) and stage 1 disease (n=1), physicians decision (n=1), patients choice (n=1) multiply relapsed disease (n=2). Progression-free survival (PFS) and overall surveival (OS) are shown in the Table. 23 patients are alive at a median follow-up of 543 days (range, 76–1598). In conclusion, GEM-P is an effective salvage regimen with long response duration in patients with relapsed or refrcatory DLBCL. The additional benefit with Rituximab on outcome warrants further studies in new and relapsed patients with DLBCL in a prospective, randomised trial. Survival OS PFS GEM-P (n=15) 3-y 40%(95%CI 16–63) 1-y 27%(95%CI 8–49) GEM-P +R (n=24) 3-y 65%(95%CI 40–82) 1-y 51% (95%CI 28–69) GEM-P ±R (n=39) 3-y 53.4% (95% CI 35–69) Median 157d (95% CI 42–271) PFS by rituximab use PFS by rituximab use

Introduction. We have previously demonstrated that presentation serum selenium predicted not only for response to treatment and duration of first remission, but also importantly for overall survival in aggressive non-Hodgkin’s lymphoma (Journal of Clinical Oncology2003, 21:2335–2341). To investigate a possible causal association as the explanation for these findings we have studied the activity of 2 selenium species, methylseleninic acid (MSA) and selenodiglutathione (SDG). We provide the first report of the activity of these two compounds in lymphoma, using a panel of human cell-lines (CRL, DHL4, SUD4 and DoHH2) and a primary human lymphoma culture system. Methods. The effects of 3-day incubations with MSA or SDG on cell proliferation and cell viability (n = 3–6) were determined by Trypan blue exclusion assay. Cell cycle distribution (including a sub-G1 apoptotic fraction), generation of reactive oxygen species (ROS) and PI/annexin staining were analysed by flow cytometry. Apoptosis was further investigated by western blotting for poly-ADP ribose polymerase (PARP) and specific caspase (8 and 9) cleavage. The activity of MSA and SDG was also investigated in a primary lymphoma culture system utilising a feeder layer of CD40 ligand expressing CHO cells irradiated prior to plating primary lymphoma cells. Results. Both MSA and SDG demonstrated cytostatic and cytotoxic effects in all 4 cell-lines studied. The EC50 values ranged from 1.0 – 10.2 μM, with the exception of the % viability EC50 for MSA in DHL4 cells (166 μM). Flow cytometry revealed cell death was associated with an increase in the sub-G1 (apoptotic) fraction, without an obvious preceding G1, S or G2/M cell cycle arrest. Apoptosis was confirmed by flow cytometric analysis of PI/annexin dual labelled cells, and was associated with PARP cleavage and involvement of both caspase 8 and 9. SDG exposure resulted in marked increases in ROS, particularly in CRL and SUD4 cells (3-5-fold increase after 30 minutes exposure to the day-3 viability EC50 concentration). The addition of n-acetyl-cysteine reduced the cytotoxic activity of SDG, but not MSA, confirming that ROS contribute to the effects seen with SDG. In 5 different 2-day primary lymphoma cultures (n = 4–6) MSA and SDG showed a concentration dependent reduction in % viability, with day-2 EC50 values of approximately 30 μM for MSA and 10 μM for SDG. Conclusions. We have demonstrated for the first time the cytostatic and cytotoxic activity of two selenium species, MSA and SDG, in human lymphoma cell-lines and primary lymphoma cells and their induction of caspase mediated apoptosis. These data suggest that selenium species may play a causal role in the success of conventional chemotherapy in aggressive lymphoma. Selenium compounds merit further investigation in the clinical management of this disease.