A shift of thermokarst lakes from carbon sources to sinks during the Holocene epoch.

Thermokarst lakes formed across vast regions of Siberia and Alaska during the last deglaciation and are thought to be a net source of atmospheric methane and carbon dioxide during the Holocene epoch. However, the same thermokarst lakes can also sequester carbon, and it remains uncertain whether carbon uptake by thermokarst lakes can offset their greenhouse gas emissions. Here we use field observations of Siberian permafrost exposures, radiocarbon dating and spatial analyses to quantify Holocene carbon stocks and fluxes in lake sediments overlying thawed Pleistocene-aged permafrost. We find that carbon accumulation in deep thermokarst-lake sediments since the last deglaciation is about 1.6 times larger than the mass of Pleistocene-aged permafrost carbon released as greenhouse gases when the lakes first formed. Although methane and carbon dioxide emissions following thaw lead to immediate radiative warming, carbon uptake in peat-rich sediments occurs over millennial timescales. We assess thermokarst-lake carbon feedbacks to climate with an atmospheric perturbation model and find that thermokarst basins switched from a net radiative warming to a net cooling climate effect about 5,000 years ago. High rates of Holocene carbon accumulation in 20 lake sediments (47 ± 10 grams of carbon per square metre per year; mean ± standard error) were driven by thermokarst erosion and deposition of terrestrial organic matter, by nutrient release from thawing permafrost that stimulated lake productivity and by slow decomposition in cold, anoxic lake bottoms. When lakes eventually drained, permafrost formation rapidly sequestered sediment carbon. Our estimate of about 160 petagrams of Holocene organic carbon in deep lake basins of Siberia and Alaska increases the circumpolar peat carbon pool estimate for permafrost regions by over 50 per cent (ref. 6). The carbon in perennially frozen drained lake sediments may become vulnerable to mineralization as permafrost disappears, potentially negating the climate stabilization provided by thermokarst lakes during the late Holocene.

Winter diet of brown trout Salmo trutta in groundwater-dominated streams: influence of environmental factors on spatial and temporal variation.

Winter diet composition of brown trout Salmo trutta was quantified from November to March in 35 temperate groundwater-dominated streams in south-eastern Minnesota, U.S.A., in relation to stream physical characteristics including drainage area, channel slope and influence of groundwater on stream thermal regime. Aquatic invertebrates made up the majority of S. trutta diet in all streams and sampling periods and individual S. trutta typically had consumed 30 or more prey items at each sampling event. Differences in diet composition were greater among streams than between sampling periods within a stream, with Gammarus spp., Brachycentrus spp., Glossosoma spp., Chironomidae and Physella spp. the most common taxa. Landscape-scale stream characteristics were not significantly associated with S. trutta consumption or diet composition. Winter was period of significant activity in groundwater-dominated streams, as S. trutta fed on a variety of aquatic prey taxa highlighting the importance of winter base-flow in moderating S. trutta populations in seasonally cold catchments.

Dosimetric consequences of pancreatic tumor motion when predetermined treatment margins are employed during intensity-modulated radiation therapy.

PURPOSE: To quantify the dosimetric consequences of pancreatic tumor motion on the pancreatic intensity-modulated radiation therapy (IMRT) plans. METHODS: Dose map of IMRT plans for 5 patients with pancreatic cancer were measured using a 2D diode array placed on a computer-controlled platform to simulate 2D pancreatic tumor motion. Dosimetric analysis was then performed to obtain IMRT quality assurance (QA) passing rates. The convolution method, which used a motion kernel to simulate 2D pancreatic motion, was also applied to the treatment and phantom verification plans for a wide range of magnitudes of motion (0.8-2.0 cm). The resulting motion-convolved verification dose maps (VDMs) were compared with the dynamic measurements to evaluate IMRT QA passing rates as well as the dose-volume histogram, the V95% of the planning target volume (PTV) and V98% of the clinical target volume (CTV). RESULTS: While CTV coverage was maintained when the simulated pancreatic tumor drifted inside the PTV with magnitudes of 1.0 cm and 1.5 cm, the V95% of the PTV was reduced by 10% and 17%, respectively. We also found that the differences between the measurements and the static VDMs increased proportional to the amplitude of motion, while the agreement between the measurements and the motion-convolved VDMs was excellent for any magnitude of motion. CONCLUSIONS: When the 4D technique is not available, predetermined margins must be used carefully to avoid possible under-dose to the target. Additionally, the phantom results show that the kernel convolution method provides an accurate evaluation of the dosimetric impact due to tumor motion and it should be employed in the planning process.

Porphyrin bleaching and PDT-induced spectral changes are irradiance dependent in ALA-sensitized normal rat skin in vivo.

Photobleaching kinetics of aminolevulinic acid-induced protoporphyrin IX (PpIX) were measured in the normal skin of rats in vivo using a technique in which fluorescence spectra were corrected for the effects of tissue optical properties in the emission spectral window through division by reflectance spectra acquired in the same geometry and wavelength interval and for changes in excitation wavelength optical properties using diffuse reflectance measured at the excitation wavelength. Loss of PpIX fluorescence was monitored during photodynamic therapy (PDT) performed using 514 nm irradiation. Bleaching in response to irradiances of 1, 5 and 100 mW cm-2 was evaluated. The results demonstrate an irradiance dependence to the rate of photobleaching vs irradiation fluence, with the lowest irradiance leading to the most efficient loss of fluorescence. The kinetics for the accumulation of the primary fluorescent photoproduct of PpIX also exhibit an irradiance dependence, with greater peak accumulation at higher irradiance. These findings are consistent with a predominantly oxygen-dependent photobleaching reaction mechanism in vivo, and they provide spectroscopic evidence that PDT delivered at low irradiance deposits greater photodynamic dose for a given irradiation fluence. We also observed an irradiance dependence to the appearance of a fluorescence emission peak near 620 nm, consistent with accumulation of uroporphyrin/coproporphyrin in response to mitochondrial damage.

Photochemical oxygen consumption, oxygen evolution and spectral changes during UVA irradiation of EMT6 spheroids.

Remarkable rates of oxygen consumption are observed via microelectrode measurements immediately upon the onset of 325 nm irradiation of multicell tumor spheroids. Consumption is irradiance dependent over the range 20-200 mW cm-2, and its magnitude is comparable to that observed previously in the same system using exogenous photosensitizers. Oscillations in the oxygen concentrations suggest that oxygen is also being evolved during irradiation. Oxygen evolution is likely the result of enzymatic dissociation of hydrogen peroxide, which is formed through UV-induced photochemistry. Irradiation of spheroids at 442 and at 514 nm produces a much more modest but detectable oxygen consumption. The dynamics of oxygen concentration changes are quite different at these wavelengths, suggesting a different photochemical mechanism. In these cases, initial oxygen depletion is followed immediately by a more gradual, monotonic increase in the oxygen concentration, consistent with irreversible photobleaching. No oscillations in the oxygen concentration are detectable. At 662 nm, no oxygen consumption was observed over the range of irradiances studied. Fluorescence spectra of cells prior to irradiation include contributions from anthranilic acid and reduced nicotinamide adenine dinucleotide (NADH). During 325 nm irradiation, anthranilic acid is rapidly and irreversibly bleached, while NADH emission undergoes only modest reduction.

Preliminary results of interstitial motexafin lutetium-mediated PDT for prostate cancer.

BACKGROUND AND OBJECTIVES: Interstitial photodynamic therapy (PDT) is an emerging modality for the treatment of solid organ disease. Our group at the University of Pennsylvania has performed extensive studies that demonstrate the feasibility of interstitial PDT for prostate cancer. Our preclinical and clinical experience is herein detailed. STUDY DESIGN/MATERIALS AND METHODS: We have treated 16 canines in preclinical studies, and 16 human subjects in a Phase I study, using motexafin lutetium-mediated PDT for recurrent prostate adenocarcinoma. Dosimetry of light fluence, drug level and oxygen distribution for these patients were performed. RESULTS: We demonstrate the safe and comprehensive treatment of the prostate using PDT. However, there is significant variability in the dose distribution and the subsequent tissue necrosis throughout the prostate. CONCLUSIONS: PDT is an attractive option for the treatment of prostate adenocarcinoma. However, the observed variation in PDT dose distribution translates into uncertain therapeutic reproducibility. Our future focus will be on the development of an integrated system that is able to both detect and compensate for dose variations in real-time, in order to deliver a consistent overall PDT dose distribution.