ALBERT

Description: This article examines whether the temporal clustering of flood events can be explained in terms of climate variability or time-varying land-surface state variables. The point process modelling framework for flood occurrence is based on Cox processes, which can be represented as Poisson processes with randomly varying rate of occurrence. In the special case that the rate of occurrence is deterministic, the Cox process simplifies to a Poisson process. Poisson processes represent flood occurrences which are not clustered. The Cox regression model is used to examine the dependence of the rate of occurrence on covariate processes. We focus on 41 stream gauge stations in Iowa, with discharge records covering the period 1950–2009. The climate covariates used in this study are the North Atlantic Oscillation (NAO) and the Pacific/North American Teleconnection (PNA). To examine the influence of land-surface forcing on flood occurrence, the antecedent 30 d rainfall accumulation is considered. In 27 out of 41 stations, either PNA or NAO, or both are selected as significant predictors, suggesting that flood occurrence in Iowa is influenced by large-scale climate indices. Antecedent rainfall, used as a proxy for soil moisture, plays an important role in driving the occurrence of flooding in Iowa. These results point to clustering as an important element of the flood occurrence process. Copyright © 2012 Royal Meteorological Society

Description: A time series of monthly mean surface temperatures taken at Svalbard airport, Spitzbergen, for the period 1912–2010 was examined for changes in melt-season length. The annual melt-season length was constructed from daily temperature estimates based on the monthly data using smoothing splines. We argue that the changes in annual melt-season length are linked to variability in regional sea surface temperatures, the mean Northern Hemisphere surface temperature and the North Atlantic Oscillation (NAO) index. A regression model for the melt-season length with these three parameters as predictors, explained about 40% of the observed variance. The annual mean melt season for the period from 1912 to 2010 was estimated to be 108 days, and the linear trend was 0.17 days/year. The risk of having positive extremes in the melt season increased with increasing Northern Hemisphere surface temperature and the regional sea surface temperatures. On the basis of our study of past observations, the 100-year return length of the melt season at Svalbard was predicted to change from the current 95% confidence interval of 131 (108, 138) days to 175 (109, 242) days with 1 °C warming of both regional sea surface temperature and the mean Northern Hemisphere surface temperature. Copyright © 2011 Royal Meteorological Society

Description: Under global warming the Caribbean is projected to be significantly drier by century's end during its primary rainy season from May to November. The PRECIS regional model is used to simulate the end-of-century (2071–2100) manifestation of the Caribbean Low Level Jet (CLLJ) under two Intergovernmental Panel on Climate Change (IPCC) global warming scenarios. The CLLJ is a feature of the Intra-American seas which during its July peak is dynamically linked to a brief mid-summer drying and interruption of the Caribbean rainy season. The regional model captures the CLLJ's present-day spatial and temporal characteristics reasonably well, simulating both the boreal winter (February) and summer (July) peaks. Under global warming there is an intensification of the CLLJ's core strength from May through November. The intensification is such that by October the CLLJ is of comparable core strength to its present-day peak in July. The persistence of the strong CLLJ beyond July and through November is linked to the perpetuation of a dry pattern in the Caribbean in the future. In contrast, the boreal winter manifestation of the CLLJ is largely unaltered in the future. Copyright © 2012 Royal Meteorological Society

Description: This article examines whether the temporal clustering of flood events can be explained in terms of climate variability or time-varying land-surface state variables. The point process modelling framework for flood occurrence is based on Cox processes, which can be represented as Poisson processes with randomly varying rate of occurrence. In the special case that the rate of occurrence is deterministic, the Cox process simplifies to a Poisson process. Poisson processes represent flood occurrences which are not clustered. The Cox regression model is used to examine the dependence of the rate of occurrence on covariate processes. We focus on 41 stream gauge stations in Iowa, with discharge records covering the period 1950–2009. The climate covariates used in this study are the North Atlantic Oscillation (NAO) and the Pacific/North American Teleconnection (PNA). To examine the influence of land-surface forcing on flood occurrence, the antecedent 30 d rainfall accumulation is considered. In 27 out of 41 stations, either PNA or NAO, or both are selected as significant predictors, suggesting that flood occurrence in Iowa is influenced by large-scale climate indices. Antecedent rainfall, used as a proxy for soil moisture, plays an important role in driving the occurrence of flooding in Iowa. These results point to clustering as an important element of the flood occurrence process. Copyright © 2012 Royal Meteorological Society

Description: This study summarizes organic carbon isotope (δ13C) and total organic carbon (TOC) data from a series of tests undertaken to provide an appropriate methodology for pre-analysis treatment of mudstones from an Upper Carboniferous sedimentary succession, in order to develop a consistent preparation procedure. The main treatments involved removing both inorganic carbonate and hydrocarbons (which might be extraneous) before δ13C and TOC analysis. The results show that decarbonating using hydrochloric acid causes significant reduction in δ13C and total carbon (TC) of the bulk material due to the removal of inorganic carbonate. These changes are most pronounced where soluble calcium carbonate (rather than Ca-Mg-Fe carbonate) is present. Deoiled samples show only slightly higher mean δ13C where visible bitumen was extracted from the bulk sample. Moreover, the isotopic signatures of the extracts are closely correlated to those of their respective bulk samples, suggesting that small yields of hydrocarbons were generated in situ with no isotopic fractionation. In addition, further δ13C and TC analyses were performed on samples where mixing of oil-based drilling mud with brecciated core material had been undertaken. Brecciated mudstone material did not display distinct isotopic signals compared to the surrounding fine-grained material. Overall we show that the most accurate assessment of bulk organic carbon isotopes and concentration in these samples can be achieved through decarbonating the material prior to measurement via the ‘rinse method’. However, our results support recent findings that pre-analysis acid treatments can cause variable and unpredictable errors in δ13C and TOC values. We believe that, despite these uncertainties, the findings presented here can be applied to paleoenvironmental studies on organic matter contained within sedimentary rocks over a range of geological ages and compositions.

Description: Mixed-layer depth (MLD) is often used in a mixed-layer heat budget to relate air-sea exchange to changes in the near-surface ocean temperature. In this study, reanalysis heat flux products and profiles from a 15 year time series of high-resolution, near-repeat expendable bathythermograph/expendable conductivity-temperature-depth (XBT/XCTD) sampling in Drake Passage are used to examine the nature of MLD variations and their impact on a first-order, one-dimensional heat budget for the upper ocean in the regions north and south of the Polar Front. Results show that temperature and density criteria yield different MLD estimates, and that these estimates can be sensitive to the choice of threshold. The difficulty of defining MLD in low-stratification regions, the large amplitude of wintertime MLD (up to 700 m in Drake Passage), and the natural small-scale variability of the upper ocean result in considerable cast-to-cast variability in MLD, with changes of up to 200 m over 10 km horizontal distance. In contrast, the heat content over a fixed-depth interval of the upper ocean shows greater cast-to-cast stability and clearly measures the ocean response to surface heat fluxes. In particular, an annual cycle in upper ocean heat content is in good agreement with the annual cycle in heat flux forcing, which explains ∼24% of the variance in heat content above 400 m depth north of the Polar Front and ∼63% of the variance in heat content south of the Polar Front.

Description: Under global warming the Caribbean is projected to be significantly drier by century's end during its primary rainy season from May to November. The PRECIS regional model is used to simulate the end-of-century (2071–2100) manifestation of the Caribbean Low Level Jet (CLLJ) under two Intergovernmental Panel on Climate Change (IPCC) global warming scenarios. The CLLJ is a feature of the Intra-American seas which during its July peak is dynamically linked to a brief mid-summer drying and interruption of the Caribbean rainy season. The regional model captures the CLLJ's present-day spatial and temporal characteristics reasonably well, simulating both the boreal winter (February) and summer (July) peaks. Under global warming there is an intensification of the CLLJ's core strength from May through November. The intensification is such that by October the CLLJ is of comparable core strength to its present-day peak in July. The persistence of the strong CLLJ beyond July and through November is linked to the perpetuation of a dry pattern in the Caribbean in the future. In contrast, the boreal winter manifestation of the CLLJ is largely unaltered in the future. Copyright © 2012 Royal Meteorological Society

Description: A step in the depth of the lithosphere base, associated with lateral variations in the upper mantle temperature structure, can trigger mantle flow that is referred to as edge-driven convection. This paper aims at outlining the implications of such edge-driven flow at a lateral temperature transition from a hot and thin to a cold and thick lithosphere of a continental back-arc. This configuration finds application in the southern Canadian Cordillera, where a hot and thin back-arc is adjacent to the cold and thick North American Craton. A series of geodynamical models tested the thermodynamical behavior of the lithosphere and upper mantle induced by a step in lithosphere thickness. The mantle flow patterns, thickness and heat flow evolution of the lithosphere, and surface topography are examined. We find that the lateral temperature transition shifts cratonward due to the vigorous edge-driven mantle flow that erodes the craton edge, unless the craton has a distinct high viscosity mantle lithosphere. The mantle lithosphere viscosity structure determines the impact of edge-driven flow on crustal deformation and surface heat flow; a dry olivine rheology for the craton prevents the edge from migrating and supports a persistent surface heat flow contrast. These phenomena are well illustrated at the transition from the hot Canadian Cordillera to craton that is supported by a rheological change and that coincides with a lateral change in surface heat flow. Fast seismic wave velocities observed in the upper mantle cratonward of the step can be explained as downwellings induced by the edge-driven flow.

Description: Abstract 3933 Background Ofatumumab is a novel fully humanized anti-CD20 monoclonal antibody with antigenic target distinct from rituximab and enhanced antibody dependent cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) with single agent activity in relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL), including heavily pretreated patients. The immunomodulatory agent (IMID) lenalidomide has been shown to induce T cell and NK cell activation and in vitro enhances rituximab induced killing of B-CLL cells via NK cell-mediated and monocyte-mediated ADCC. We hypothesized that the sequential treatment of patients with ofatumumab and lenalidomide would provide optimal pharmacodynamic interaction and be active in R/R patients previously treated with rituximab containing regimens. Methods Eligibility criteria included confirmed diagnosis of R/R CLL meeting criteria for treatment, prior therapy containing rituximab, age≥ 18 years, ECOG performance status ≤ 2 adequate hepatic, renal and bone marrow function and willingness to comply with the required birth control measures. Patients were excluded if they had been previously exposed to any of the experimental agents, had active hepatitis B or carried HIV. Treatment consisted of ofatumumab 2000 mg (300 mg on the first cycle) intravenously on day 1 and lenalidomide 10 mg (5mg on the first cycle) on days 8–28. Treatment was administered for up to 6 cycles of 28 days duration. Patients received prophylaxis with acyclovir and trimethoprim + sulfamethoxazole. Toxicity was assessed according to CTC v.4.0 and response was evaluated following the 2008 National Cancer Institute Working Group criteria. Results Seventeen patients have been enrolled and 14 have sufficient follow-up to be assessed for response. Median age of patients was 65 years (range 51–80). Median number of prior lines of therapy was 2 (range 1–4) and median baseline white blood cell count was 75,000/mm3. The proportions of cases with unmutated IgvH chain and positive ZAP-70 expression were 15/17 (88%) and 13/16 (81%), respectively. There were 4/16 (25%) cases with del17p and 4/16 (25%) with del11q detected by fluorescence in situ hybridization (FISH). Thirteen cases (76%) were refractory to, or had relapsed after treatment containing a purine analogue. The most frequent adverse event (AE) 〉 Grade 1 was tumor flare reaction (TFR), seen in 8/14 (57%) patients and infusion reactions seen in 6/14 (43%) patients. Four patients with TFR were managed successfully with non-steroidal anti inflammatory agents while 4 required glucocorticoids allowing continuation of therapy in all patients. The most common Grade 3+4 AE was neutropenia (11/14, 79%) although it was associated with infection in only 1 episode. One subject had early discontinuation due to toxicity (elevation in AST and ALT precluding further administration of ofatumumab). The majority of patients (11/14, 79%) required dose reduction or could not have the planned dose increase of lenalidomide after cycle 1 due to hematological toxicity. Overall 6/14 (43%) had objective response and 3/14 (21%) had stable disease for an overall clinical benefit in 64% of patients. All patients with TFR〉 Grade 1 had at least stable disease. Conclusion Intracycle sequential ofatumumab plus lenalidomide is well tolerated in advanced, high-risk CLL except for high rate of TFR and neutropenia without infection. Sequential ofatumumab and lenalidomide may be associated with higher rate of TFR than concomitant therapy. Approximately half the patients treated with this combination will obtain disease control. Further investigation is warranted in earlier lines and/or for more prolonged therapy. Disclosures: Costa: GSK: Research Funding. Off Label Use: Lenalidomide for treatment of CLL.