Imaging biomarker roadmap for cancer studies O'Connor, James P B; Aboagye, Eric O; Adams, Judith E ...
Nature reviews. Clinical oncology,
03/2017, Volume:
14, Issue:
3
Journal Article
Peer reviewed
Open access
Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection ...fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.
As part of the KErguelen: compared study of the Ocean and the Plateau in Surface water (KEOPS) project in late summer 2005, we examine the phytoplankton community composition and associated primary ...production in the waters surrounding the Kerguelen Archipelago, with the emphasis on two contrasted environments: (i) the Kerguelen Plateau, where a large bloom occurs annually, and (ii) the high-nutrient low-chlorophyll (HNLC) offshore waters. A biomarker pigment approach was used to assess the community composition in terms of chlorophyll biomass of three phytoplankton size classes, namely micro-, nano-, and picophytoplankton. The second objective was to evaluate a global class-specific approach for estimating the contribution of the three pigment-based size classes to the primary production in the study area. To do so, primary production rates associated with each phytoplankton class were computed from the class-specific chlorophyll biomass coupled to a class-specific primary production model, and compared with in situ measurements of size-fractionated
13C-based primary production. The iron-enriched bloom region was dominated by microphytoplankton (diatoms), which contributed 80–90% to the total primary production (of ≈1
g
C
m
−2
d
−1). In the HNLC area, the primary production was about 0.30
g
C
m
−2
d
−1, mainly (65%) achieved by small diatoms and nanoflagellates. The model results show a good overall agreement between predicted and measured total primary production rates. In terms of size classes, agreements were higher for the bloom region than for the HNLC waters. Discrepancies in this complex iron-limited area may be explained essentially by the smaller size of diatoms, or a different set of photophysiological properties.
This paper provides a description of the physical and chemical properties (temperature, salinity, macro-nutrient, and oxygen concentrations) and bulk biomass indicators (chlorophyll and beam ...attenuation) prevailing in the subantarctic zone and polar front zones south of Tasmania (Australia) during the ‘Sensitivity of the subantarctic zone to environmental change’ (SAZ-Sense) expedition carried out in the austral summer of 2007. Phytoplankton biomass showed a characteristic north–south gradient of decreasing chlorophyll from the subantarctic zone to Polar Frontal Zone, as well as a zonal gradient in the northern subantarctic zone, with an increase in chlorophyll from southwest to southeast of Tasmania. The representativeness of the observations was assessed by comparison to previous studies including satellite observation of chlorophyll biomass over a 10-year period. We consider the possible role of spatial differences in: (i) ocean water masses and frontal systems, (ii) upper mixed layer stratification at three process stations, and (iii) nutrient availability, in controlling the observed variations in phytoplankton biomass in the region. Zonal gradients of the basic oceanographic physical and chemical conditions in the subantarctic zone were relatively small and therefore unlikely to control the three-fold west-to-east differences observed in the accumulation of phytoplankton biomass. The zonal variation in subantarctic zone chlorophyll biomass appears to be driven at least partly by greater micro-nutrient (iron) supply to the waters east of Tasmania, as reported also by others (
Bowie et al., 2009; Mongin et al., 2011a). Despite this condition, the region of higher phytoplankton biomass to the southeast of Tasmania was only marginally more productive than the region of lower biomass west of Tasmania and south of the polar front, and exported less particulate carbon than the lower biomass waters (
Jacquet et al., 2011).
The Sub-Antarctic Zone (SAZ) in the Southern Ocean provides a significant sink for atmospheric CO
2 and quantification of this sink is therefore important in models of climate change. During the ...SAZ-Sense (Sub-Antarctic Sensitivity to Environmental Change) survey conducted during austral summer 2007, we examined CO
2 sequestration through measurement of gross primary production rates using
14C. Sampling was conducted in the SAZ to the south-west and south-east of Tasmania, and in the Polar Frontal Zone (PFZ) directly south of Tasmania. Despite higher chlorophyll biomass off the south-east of Tasmania, production measurements were similar to the south-west with rates of 986.2±500.4 and 1304.3±300.1
mg
C
m
−2
d
−1, respectively. Assimilation numbers suggested the onset of cell senescence by the time of sampling in the south-east, with healthy phytoplankton populations to the south-west sampled three weeks earlier. Production in the PFZ (475.4±168.7
mg
C
m
−2
d
−1) was lower than the SAZ, though not significantly. The PFZ was characterised by a defined deep chlorophyll maximum near the euphotic depth (75
m) with low production due to significant light limitation. A healthy and less light-limited phytoplankton population occupied the mixed layer of the PFZ, allowing more notable production there despite lower chlorophyll. A hypothesis that iron availability would enhance gross primary production in the SAZ was not supported due to the seasonal effect that masked possible responses. However, highest production (2572.5
mg
C
m
−2
d
−1) was measured nearby in the Sub-Tropical Zone off south-east Tasmania in a region where iron was likely to be non-limiting (
Bowie et al., 2009. Biogeochemical iron budgets of the Southern Ocean south of Australia: decoupling of iron and nutrient cycles in the subantarctic zone by the summertime supply. Global Biogeochemical Cycles 23(4), doi:10.1029/2009GB003500).
Climate-driven changes are expected to alter the hydrography of the Sub-Antarctic Zone (SAZ) and Polar Frontal Zone (PFZ) south of Australia, in which distinct regional environments are believed to ...be responsible for the differences in phytoplankton biomass in these regions. Here, we report how the dynamic influences of light, iron and temperature, which are responsible for the photophysiological differences between phytoplankton in the SAZ and PFZ, contribute to the biomass differences in these regions. High effective photochemical efficiency of photosystem II (F'(q)/F'(m)0.4), maximum photosynthesis rate (P(B)(max)), light-saturation intensity (E(k)), maximum rate of photosynthetic electron transport (1/Symbol: see textPSII), and low photoprotective pigment concentrations observed in the SAZ correspond to high chlorophyll a and iron concentrations. In contrast, phytoplankton in the PFZ exhibits low F'(q)/F'(M) (~ 0.2) and high concentrations of photoprotective pigments under low light environment. Strong negative relationships between iron, temperature, and photoprotective pigments demonstrate that cells were producing more photoprotective pigments under low temperature and iron conditions, and are responsible for the low biomass and low productivity measured in the PFZ. As warming and enhanced iron input is expected in this region, this could probably increase phytoplankton photosynthesis in this region. However, complex interactions between the biogeochemical processes (e.g. stratification caused by warming could prevent mixing of nutrients), which control phytoplankton biomass and productivity, remain uncertain.
Microzooplankton species composition and grazing rates on phytoplankton were investigated along a transect between ∼46 and 67°S, and between 140 and 145°E. Experiments were conducted in summer ...between November 2nd and December 14th in 2001. The structure of the microbial food web changed considerably along the transect and was associated with marked differences in the physical and chemical environment encountered in the different water masses and frontal regions. On average microzooplankton grazing experiments indicated that 91%, 102%, and 157%, (see results) of the phytoplankton production would be grazed in the <200, <20 and <2
μm size fractions, respectively, indicating microzooplankton grazing was potentially constraining phytoplankton populations (<200
μm) along most of the transect. Small ciliates in general and especially oligotrich species declined in importance from the relatively warm, Southern Subtropical Front waters (6.8
μg
C/L) to the colder waters of the southern branch of the Polar Front (S-PF), (∼0.5
μg
C/L) before increasing again near the Antarctic landmass. Large changes in microzooplankton dominance were observed, with heterotrophic nanoflagellates (HNF), ciliates and larger dinoflagellates having significant biomass in different water masses. HNF were the dominant grazers when chlorophyll
a was low in areas such as the Inter-Polar Frontal Zone (IPFZ), while in areas of elevated biomass such as the S-PF and Southern Antarctic Circumpolar Current (SACC), a mix of copepod nauplii and large heterotrophic and mixotrophic dinoflagellates tended to dominate the grazing community. In the S-PF and SACC water masses the tight coupling observed between the microzooplankton grazers and phytoplankton populations over most of the rest of the transect was relaxed. In these regions grazing was low on the >20
μm size fraction of chlorophyll
a, which dominated the biomass, while smaller diatoms and nanoplankton in the <20
μm size fraction were still heavily grazed. The lack of grazing pressure on large phytoplankton contributes to this region's potential to export carbon with larger cells known to have higher sinking rates.
This paper examines the costs and determinants of order aggressiveness. Aggressive orders have larger price impacts but smaller opportunity costs than passive orders. Price impacts are amplified by ...large orders, small firms, and volatile stock prices. To minimize the implementation shortfall, the optimal strategy is to enter buy (sell) orders at the bid (ask). Aggressive buy (sell) orders tend to follow other aggressive buy (sell) orders and occur when bid–ask spreads are narrow and depth on the same (opposite) side of the limit book is large (small). Aggressive buys are more likely than sells to be motivated by information.
The southern hemisphere marine Aerosol Characterization Experiment (ACE 1) was the first of a series of experiments that will quantify the chemical and physical processes controlling the evolution ...and properties of the atmospheric aerosol relevant to radiative forcing and climate. The goals of this series of process studies are to reduce the overall uncertainty in the calculation of climate forcing by aerosols and to understand the multiphase atmospheric chemical system sufficiently to be able to provide a prognostic analysis of future radiative forcing and climate response. ACE 1, which was conducted from November 15 to December 14, 1995, over the southwest Pacific Ocean, south of Australia, quantified the chemical, physical, radiative, and cloud nucleating properties and furthered our understanding of the processes controlling the aerosol properties in this minimally polluted marine atmosphere. The experiment involved the efforts of scientists from 45 research institutes in 11 countries.
Primary productivity was measured in the Indian Sector of the Southern Ocean (30° to 80°E) as part of a multi-disciplinary study during austral summer; Baseline Research on Oceanography, Krill and ...the Environment, West (BROKE-West Survey, 2006). Gross integrated (0–150
m) productivity rates within the marginal ice zone (MIZ) were significantly higher than within the open ocean, with averages of 2110.2±1347.1 and 595.0±283.0
mg
C
m
−2
d
−1, respectively. In the MIZ, high productivity was associated with shallow mixed-layer depths and increased P
max up to 5.158
mg
C (mg
chl
a)
−1
h
−1. High Si:N drawdown ratios in the open ocean (4.1±1.5) compared to the MIZ (2.2±0.79) also suggested that iron limitation was important for the control of productivity. This was supported by higher F
v/F
m ratios in the MIZ (0.50±0.11 above 40
m) compared to the open ocean (0.36±0.08). As well, in the open ocean there were regions of elevated productivity associated with the seasonal pycnocline where iron availability was possibly increased. High silicate drawdown in the north-eastern section of the BROKE-West survey area suggested significant diatom growth and was linked to the presence of the southern Antarctic Circumpolar Current front (sACCF). However, low assimilation numbers (12.8–23.2
mg
C
mg
chl
a
−1
d
−1) and F
v/F
m ratios indicated that cells were senescent with initial growth occurring earlier in the season. In the western section of the survey area within the MIZ, high NO
3 drawdown but relatively low silicate drawdown were associated with a
Phaeocystis bloom. NO
3 concentrations were strongly negatively correlated with column-integrated productivity and chlorophyll biomass which was expected given the requirement for this nutrient by all phytoplankton groups. Regardless, concentrations of both NO
3 and silicate were above limiting levels within the entire BROKE-West survey area (N>15.7
μM, Si>18.3
μM) supporting the high-nutrient low-chlorophyll status of the Southern Ocean.
In situ primary productivity (PP) in the Sub-Antarctic Zone (SAZ) and the Polar Frontal Zone (PFZ) south of Australia was estimated using fast repetition rate fluorometry (FRRF). FRRF-derived PP at ...Process station 3 (P3) southeast of Tasmania (46°S, 153°E) were higher than P1 in the southwest of Tasmania (46°S, 140°E) and P2 in the Polar Frontal Zone (54°S, 146°E). The FRRF-derived PP rates were well correlated with
14C-uptake rates from one-hour incubations (
r
2=0.85, slope=1.23±0.05,
p<0.01,
n=85) but the relationship between both methods differed vertically and spatially. There was a linear relationship between FRRF-based PP and
14C-based PP under light-limited conditions in deeper waters. Under light-saturated conditions near the surface (0–45
m), the relationship was less clear. This was likely associated with the effects of physiological processes such as cyclic electron flow and the Mehler reaction, which are stimulated at high irradiance. Our results indicate that FRRF can be used to estimate photosynthesis rates in the SAZ and PFZ but to derive an accurate estimation of C-fixation requires a detailed understanding of the physiological properties of the cells and their response to oceanographic parameters under different environmental conditions.
PDF
