Comparison of Tumor Shrinkage and Cumulative Dose Distribution for Lung Cancers

Background: The physical characteristic of protons is that they deliver most of their radiation dose to the target volume and deliver no dose to the normal tissue distal to the tumor. Previously, numerous studies have shown unique advantages of proton therapy over intensity-modulated radiation therapy (IMRT) in conforming dose to the tumor and sparing dose to the surrounding normal tissues and the critical structures in many clinical sites. However, proton therapy is known to be more sensitive to treatment uncertainties such as inter- and intra-fractional variations in patient anatomy. To date, no study has clearly demonstrated the effectiveness of proton therapy compared with the conventional IMRT under the consideration of both respiratory motion and tumor shrinkage in non-small cell lung cancer (NSCLC) patients. Purpose: This thesis investigated two questions for establishing a clinically relevant comparison of the two different modalities (IMRT and proton therapy). The first question was whether or not there are any differences in tumor shrinkage between patients randomized to IMRT versus passively scattered proton therapy (PSPT). Tumor shrinkage is considered a standard measure of radiation therapy response that has been widely used to gauge a short-term progression of radiation therapy. The second question was whether or not there are any differences between the planned dose and 5D dose under the influence of inter- and intra-fractional variations in the patient anatomy for both modalities. Methods: A total of 45 patients (25 IMRT patients and 20 PSPT patients) were used to quantify the tumor shrinkage in terms of the change of the primary gross tumor volume (GTVp). All patients were randomized to receive either IMRT or PSPT for NSCLC. Treatment planning goals were identical for both groups. All patients received 5 to 8 weekly repeated 4-dimensional computed tomography (4DCT) scans during the course of radiation treatments. The original GTVp contours were propagated to T50 of weekly 4DCT images using deformable image registration and their absolute volumes were measured. Statistical analysis was performed to compare the distribution of tumor shrinkage between the two population groups. In order to investigate the difference between the planned dose and the 5D dose with consideration of both breathing motion and anatomical change, we re-calculated new dose distributions at every phase of the breathing cycle for all available weekly 4DCT data sets which resulted 50 to 80 individual dose calculations for each of the 7 patients presented in this thesis. The newly calculated dose distributions were then deformed and accumulated to T50 of the planning 4DCT for comparison with the planned dose distribution. Results: At the end of the treatment, both IMRT and PSPT groups showed mean tumor volume reductions of 23.6% ( 19.2%) and 20.9% ( 17.0 %) respectively. Moreover, the mean difference in tumor shrinkage between two groups is 3% along with the corresponding 95% confidence interval, [-8%, 14%]. The rate of tumor shrinkage was highly correlated with the initial tumor volume size. For the planning dose and 5D dose comparison study, all 7 patients showed a mean difference of 1 % in terms of target coverage for both IMRT and PSPT treatment plans. Conclusions: The results of the tumor shrinkage investigation showed no statistically significant difference in tumor shrinkage between the IMRT and PSPT patients, and the tumor shrinkage between the two modalities is similar based on the 95% confidence interval. From the pilot study of comparing the planned dose with the 5D dose, we found the difference to be only 1%. Overall impression of the two modalities in terms of treatment response as measured by the tumor shrinkage and 5D dose under the influence of anatomical change that were designed under the same protocol (i.e. randomized trial) showed similar result.

An individual based model spatial distribution, production and biomass for Calanus finmarchicus in the Norwegian Sea

The copepod Calanus finmarchicus is the dominant species of the meso-zooplankton in the Norwegian Sea, and constitutes an important link between the phytoplankton and the higher trophic levels in the Norwegian Sea food chain. An individualbased model for C. finmarchicus, based on super-individuals and evolving traits for behaviour, stages, etc., is two-way coupled to the NORWegian ECOlogical Model system (NORWECOM). One year of modelled C. finmarchicus spatial distribution, production and biomass are found to represent observations reasonably well. High C. finmarchicus abundance is found along the Norwegian shelf-break in the early summer, while the overwintering population is found along the slope and in the deeper Norwegian Sea basins. The timing of the spring bloom is generally later than in the observations. Annual Norwegian Sea production is found to be 29 million tonnes of carbon and a production to biomass (P/B) ratio of 4.3 emerges. Sensitivity tests show that the modelling system is robust to initial values of behavioural traits and with regards to the number of super-individuals simulated given that this is above about 50,000 individuals. Experiments with the model system indicate that it provides a valuable tool for studies of ecosystem responses to causative forces such as prey density or overwintering population size. For example, introducing C. finmarchicus food limitations reduces the stock dramatically, but on the other hand, a reduced stock may rebuild in one year under normal conditions. The NetCDF file contains model grid coordinates and bottom topography.

Distribution of abundance of planktic foraminifera and calcareous nannofossils at DSDP Sites 17-167 and 62-463

New paleomagnetic and paleontologic data from Pacific DSDP Sites 463 and 167 define the magnetic reversals that predate the Cretaceous Normal Polarity Superchron (K-N). Data from Mid-Pacific Mountain Site 463 provide the first definition of polarity chron M0 in the Pacific deep-sea sedimentary record. Foraminiferal biostratigraphy suggests that polarity chron M0 is contained entirely within the lower Aptian Hedbergella similis Zone, in agreement with foraminiferal data from the Italian Southern Alps and Atlantic Ocean. Nannofossil assemblages also suggest an early Aptian age for polarity chron M0, contrary to results from the Italian Umbrian Apennines and Southern Alps, which place polarity chron M0 on the Barremian-Aptian boundary. Biostratigraphic dating discrepancies caused by the time-transgressive, preservational, or provincial nature of paleontological species might be reconciled by the use of magnetostratigraphy, specifically polarity chron M0 which lies close to the Barremian-Aptian boundary. At Magellan Rise Site 167, five reversed polarity zones are recorded in Hauterivian to Aptian sediments. Correlation with M-anomalies is complicated by synsedimentary and postsedimentary sliding about 25 m.y. after basement formation, producing gaps in, and duplications of, the stratigraphic sequence. The magnitude and timing of such sliding must be addressed when evaluating the stratigraphy of these oceanic-rise environments.

Distribution of benthos in late Quaternary turbidite layers of sediment cores from the North-West African continental margin

The CaCO3-contents and the fractions > 40 µm have been analysed from 5 kastenloten, one piston core and two kastengreifer taken between Senegal and Cape Verde Islands. Numerous benthonic and planktonic organisms and different terrigenous components have been distinguished. The four cores off Senegal reach middle Wuerm sediments; cores GIK12329-6 and TAG72-1 reach the V-zone and core GIK12331-4 the X-zone (Eem); the two kastengreifer contain sediments of Holocene age. Correlation of the cores has been made. Holocene sedimentation rates decrease from the shallow cores (6-11 cm/1000 years) to the deep-sea (1-2 cm/1000 years). The following climatic variations could be deduced from the sediments off the Senegal: during Holocene climate was in general as today, the Senegal river transporting fine grained material to the sea. The upper Wuerm was arid with no river influence but with red dune sand transported to the continental slope. During middle Wuerm the climate was humid again. The deep-sea cores have been influenced by eolian material from arid regions during glacial and interglacial periods, indicated by relatively high "Wuestenquarz-numbers". However, during Wuerm "Wuestenquarz-numbers" are higher than during Holocene and Eem, indicating that more intensely red coloured sediment was exposed to wind activity on the continent during this period. Varying amounts of terrigenous material and CaCO3-contents indicate varying wind strengths (lower in Holocene and Eem than during Wuerm). The boundary between humid and arid Wuerm climate was at approximately 20 °N. Influence of upwelling is difficult to establish in the sediments off Senegal, because river influence, while increasing fertility also dilutes the diatoms which are typical for upwelling. High amounts of organic carbon, low plankton/benthos ratios of foraminifers and low plankton foraminifer/radiolarian ratios in Holocene sections might be interpreted as influenced by upwelling. Turbidites occur in cores 72 and 31 and at the Holocene/Pleistocene boundary of core GIK12329-6. Their composition indicates provenance from the continental shelf of the Cape Verde Islands for core 31 and the continental shelf and slope off Senegal for core TAG72-1. Volcanic material, rare in the normal pelagic sediment of core GIK12331-4 is more frequent in the turbidites.

Age determination and grain size distribution of sediment core GeoB3375-1

The palaeoclimatic conditions during the Last Glacial Maximum (LGM) of southern South America and especially latitudinal shifts of the southern westerly wind belt are still discussed controversially. Longer palaeoclimatic records covering the Late Quaternary are rare. A particularly sensitive area to Late Quaternary climatic changes is the Norte Chico, northern Chile, because of its extreme climatic gradients. Small shifts of the present climatic zonation could cause significant variations of the terrestrial sedimentary environment which would be recorded in marine terrigenous sediments. To unveil the history of shifting climatic zones in northern Chile, we present a sedimentological study of a marine sediment core (GeoB 3375-1) from the continental slope off the Norte Chico (27.5°S). Sedimentological investigations include bulk- and silt grain-size determinations by sieving, Atterberg separation, and detailed SediGraph analyses. Additionally, clay mineralogical parameters were obtained by X-ray diffraction methods. The 14C-dated core, covering the time span from approximately 10,000 to 120,000 cal. yr B.P., consists of hemipelagic sediments. Terrigenous sedimentological parameters reveal a strong cyclicity, which is interpreted in terms of variations of sediment provenance, modifications of the terrestrial weathering regimes, and modes of sediment input to the ocean. These interpretations imply cyclic variations between comparatively arid climates and more humid conditions with seasonal precipitation for northern Chile (27.5°S) through the Late Quaternary. The cyclicity of the terrigenous sediment parameters is strongly dominated by precessional cycles. For the palaeoclimatic signal, this means that more humid conditions coincide with maxima of the precession index, as e.g. during the LGM. Higher seasonal precipitation for this part of Chile is most likely derived from frontal winter rain of the Southern Westerlies. Thus, the data presented here favour not only an equatorward shift of this atmospheric circulation system during the LGM, but also precession-controlled latitudinal movements throughout the Late Quaternary. Precessional forcing of latitudinal movements of the westerly atmospheric circulation system may be conceivable through teleconnections to the Northern Hemisphere monsoonal system in the Atlantic Ocean region.

Paleocene radiolarian distribution and biostratigraphy from offshore eastern New Zealand

A 100-m-thick Paleocene sequence of mainly pelagic sediments at ODP Site 1121, on the eastern flanks of the Campbell Plateau, contains few to common radiolarians of relatively low diversity in the lower 40 m (Early to early Late Paleocene) and abundant, diverse radiolarian assemblages in the upper 60 m (mid-Late Paleocene). The 150 taxa recorded from the entire Paleocene interval are thought to under-represent the actual species diversity by at least one half as many morphotypes have not been differentiated below the level of genus. Assemblages in the lower 40 m are similar to those described from onland New Zealand and DSDP Site 208 (northern Lord Howe Rise); they are correlated with South Pacific radiolarian zones RP4 and RP5. Assemblages in the upper 60 m differ from other known Late Paleocene assemblages in the great abundance of plagiacanthids and cycladophorids. Similarities are noted with later Cenozoic cool-water assemblages. This upper interval is correlated with South Pacific zone RP6, as revised herein, based on comparison with faunas from Site 208 and Marlborough, New Zealand. The interval is also correlated with the upper part of North Atlantic zone RP6 (RP6b-c) based on the presence of Aspis velutochlamydosaurus, Plectodiscus circularis and Pterocodon poculum. Other species, such as Buryella tetradica and Buryella pentadica, are valuable for local correlation but exhibit considerable diachroneity between the Pacific, Indian and Atlantic Oceans. An age model for the Paleocene interval at Site 1121, based on well-constrained nannofossil and radiolarian datums, indicates that the rate of compacted sediment accumulation doubles from 15 to 30 mm/ka at the RP5/RP6 zonal boundary. In large part this is due to a sudden and pronounced increase in accumulation rates for all siliceous fossils; radiolarians and larger diatoms increase from <100 to >10 000 specimens/cm2/ka. This apparent increase in biosiliceous productivity is age-equivalent to a mid-Paleocene cooling event (57-59 Ma) identified from global stable isotope records that is associated with the heaviest delta13C values for the entire Cenozoic.

Tab. 1: Distribution of important species along a topographical transect in a siliceous boulder talus near Vårsolbukta, Bellsund

The vegetation pattern of siliceous boulder snow beds (Dicranoweision crispulae all. nov. prov.) of Svalbard was investigated by using transect studies in several places on Spitsbergen. Dicranoweisia crispula is the best diagnostic species. It is found throughout the whole snow bed, is a good differential species against Racomitrium lanuginosum communities above the snow bed, and does not occur on basic rocks. Three Andreaea spp. are also among the most important members of these communities. They are all acidophilous, but with different pH preferences. Eight weakly acidophilous species lacking both on basic and on gneissic/granitic rocks, are reported from Svalbard. Half of these are characteristic species of Dicranoweision crispulae on Svalbard.

Distribution and abundance of nannofossils in DSDP Site 89-585

Late Aptian through middle Eocene nannofossil assemblages were recovered from a continuously cored section at Site 585. Poorly preserved assemblages of low diversity were observed in samples taken throughout both upper Aptian and/or lower Albian sandstone and mudstone and middle Cenomanian to lower Turonian claystone at the base of this section. A 70-m interval barren of nannofossils separates these poorly preserved assemblages from those recovered from an upper Campanian chalk farther uphole. This chalk marks the most significant change in carbonate deposition at this site, and deposition of interbedded zeolitic claystone and sediment of varied nannofossil content proceeded without major interruption until the early Paleocene (Fasciculithus tympaniformis Zone, CP4). A middle Eocene chalk (dated by nannofossils) unconformably overlies lower Paleocene sediment in both Holes 585 and 585A. Only a few interbeds of zeolitic claystone are present within 100 m of nannofossil-rich sediment above this unconformity. This entire interval is cautiously assigned to the Discoaster sublodoensis Zone (CP 12), which indicates a sedimentation rate almost an order of magnitude higher than expected from normal pelagic sedimentation. The most obvious feature of the assemblages examined from these cores is the amount of reworked material. Rare Nannoconus elongatus and Braarudosphaera sp. in several upper Campanian to middle Eocene samples demonstrate the contribution of pelagic material from upslope and, along with other reworked species throughout the Upper Cretaceous samples examined, provide evidence contradictory to an excursion of the calcium compensation depth to deep basinal settings in the western Pacific during the Campanian-Maestrichtian time (Thierstein, 1979). The overwhelming dominance of reworked species in all middle Eocene samples examined and the persistence of these assemblages throughout such a large thickness of sediment suggest that currents that redeposited material intensified at this time and may be associated with the formation of the lower Paleocene/middle Eocene unconformity at this site. A single surface core of calcareous ooze taken from Hole 585A dated as early Pleistocene contains abundant and well-preserved late Miocene and Pliocene species.

Grain-size distribution and frictional behaviour of sediment cores from the Nice Slope

The upper shelf of the landslide-prone Ligurian Margin (Western Mediterranean Sea) off Nice well-known for the 1979 Airport Landslide is a natural laboratory to study preconditioning factors and trigger mechanisms for submarine landslides. For this study low-stress ring shear experiments have been carried out on a variety of sediments from >50 gravity cores to characterise the velocity-dependent frictional behaviour. Mean values of the peak coefficient of friction vary from 0.46 for clay-dominated samples (53 % clay, 46 % silt, 1 %) sand up to 0.76 for coarse-grained sediments (26 % clay, 57 % silt, 17 % sand). The majority of the sediments tested show velocity strengthening regardless of the grain size distribution. For clayey sediments the peak and residual cohesive strength increases with increasing normal stress, with values from 1.3 to 10.6 kPa and up to 25 % of all strength supported by cohesive forces in the shallowmost samples. A pseudo-static slope stability analysis reveals that the different lithologies (even clay-rich material with clay content >=50 %) tested are stable up to slope angles <26° under quasi-drained conditions.