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Background: In prey, patterns of individual habitat selection and movement can be a consequence of an individuals' anti-predator behavior. Adjustments of anti-predator behavior are important for prey to increase their survival. Hunters may alter the anti-predator behavior of prey. In long-lived animals, experience may cause behavioral changes during individuals' lifetime, which may result in altered habitat selection and movement. Our knowledge of which specific events related to hunting activity induce behavioral changes in solitary living species is still limited., Methods: We used offspring loss in a solitary and long-lived ungulate species, moose (Alces alces), as our model system. We investigated whether offspring loss to hunters induces behavioral changes in a species subjected to heavy human harvest but free from natural predation. To test for behavioral change in relation to two proxies for experience (calf fate and age), we combined movement data from 51 adult female moose with data on their offspring survival and female age. We tested for adjustments in females' habitat selection and movement following calf harvest using Hidden Markov Models and integrated Step Selection Analysis to obtain behavioral state specific habitat selection coefficients., Results: We found that females with a harvested calf modified habitat selection and movement during the following hunting season. Female moose selected for shorter distance to roads during the night, selected for shorter distance to forests and greater distance to human settlements following calf harvest than females who had not lost a calf. The survival of twins in a given hunting season was related to female age. Older females we more likely to have twins survive the hunting season., Conclusions: Our findings suggest that losing offspring to human harvest imposes behavioral changes in a long-lived ungulate species, leading to adjustments in females' habitat selection and movement behavior, which may lower the risk of encountering hunters. In our study, female moose that experienced calf loss selected for lower distance to forest and selected for greater distance to human settlements during periods of high hunting pressure compared to females without the experience of calf loss during the previous hunting season. We interpret this as potential learning effects., (© 2024. The Author(s).)

Conservation of biodiversity requires in-depth knowledge of trait-environment interactions to understand the influence the environment has on species assemblages. Saproxylic beetles exhibit a wide range of traits and functions in the forest ecosystems. Understanding their responses to surrounding environment thus improves our capacity to identify habitats that should be restored or protected. We investigated potential interactions between ecological traits in saproxylic beetles (feeding guilds and habitat preferences) and environmental variables (deadwood, type and age of surrounding forest). We sampled beetles from 78 plots containing newly created high stumps of Scots pine and Silver birch in boreal forest landscapes in Sweden for three consecutive years. Using a model based approach, our aim was to explore potential interactions between ecological traits and the surrounding environment at close and distant scale (20 m and 500 m radius). We found that broadleaf-preferring beetle species are positively associated with the local broadleaf-originated deadwood and broadleaf-rich forests in the surrounding landscapes. Conifer-preferring species are positively associated with the local amount of coniferous deadwood and young and old forests in the surrounding landscape. Fungivorous and predatory beetles are positively associated with old forests in the surrounding landscapes. Our results indicate that both local amounts of deadwood and types of forests in the landscape are important in shaping saproxylic beetle communities. We particularly highlight the need to increase deadwood amounts of various qualities in the landscape, exempt older forests from production and to increase broadleaf-rich habitats in order to meet different beetle species' habitat requirements. Trait responses among saproxylic beetles provide insights into the significance of broadleaf forest and dead wood as essential attributes in boreal forest restoration, which helps conservation planning and management in forest landscapes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The careful selection of ungulate calving sites to improve offspring survival is vital in the face of predation. In general, there is limited knowledge to which degree predator presence and prey's individual experience shape the selection of calving sites. Predator presence influences the spatiotemporal risk of encountering a predator, while individual experiences with previous predation events shape perceived mortality risks. We used a multi-year movement dataset of a long-lived female ungulate (moose, Alces alces , n  = 79) and associated calf survival to test how predator presence (i.e., encounter risk) and females' individual experiences with previous calf mortality events affected their calving site selection and site fidelity. Using data from areas with and without Scandinavian brown bear ( Ursus arctos ) predation, we compared females' calving site selection using individual-based analyses. Our findings suggest two things. First, bear presence influences calving site selection in this solitary living ungulate. Females in areas with bears were selected for higher shrub and tree cover and showed lower site fidelity than in the bear-free area. Second, the individual experience of calf loss changes females' selection the following year. Females with lost calves had a lower site fidelity compared to females with surviving calves. Our findings suggest that increased vegetation cover may be important for reducing encounter risk in bear areas, possibly by improving calf concealment. Lower site fidelity might represent a strategy to make the placement of calving sites less predictable for predators. We suggest that bear presence shapes both habitat selection and calving site fidelity in a long-lived animal, whereas the effect of individual experience with previous calf loss varies. We encourage further research on the relevance of female experience on the success of expressed anti-predator strategies during calving periods., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Although the advent of high-resolution GPS tracking technology has helped increase our understanding of individual and multispecies behavior in wildlife systems, detecting and recording direct interactions between free-ranging animals remains difficult. In 2023, we deployed GPS collars equipped with proximity sensors (GPS proximity collars) on brown bears ( Ursus arctos ) and moose ( Alces alces ) as part of a multispecies interaction study in central Sweden. On 6 June, 2023, a collar on an adult female moose and a collar on an adult male bear triggered each other's UHF signal and started collecting fine-scale GPS positioning data. The moose collar collected positions every 2 min for 89 min, and the bear collar collected positions every 1 min for 41 min. On 8 June, field personnel visited the site and found a female neonate moose carcass with clear indications of bear bite marks on the head and neck. During the predation event, the bear remained at the carcass while the moose moved back and forth, moving toward the carcass site about five times. The moose was observed via drone with two calves on 24 May and with only one remaining calf on 9 June. This case study describes, to the best of our knowledge, the first instance of a predation event between two free ranging, wild species recorded by GPS proximity collars. Both collars successfully triggered and switched to finer-scaled GPS fix rates when the individuals were in close proximity, producing detailed movement data for both predator and prey during and after a predation event. We suggest that, combined with standard field methodology, GPS proximity collars placed on free-ranging animals offer the ability for researchers to observe direct interactions between multiple individuals and species in the wild without the need for direct visual observation., Competing Interests: We have no competing interests., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Gestation and lactation have high energetic requirements. Up to three-fourths of the gestation period in moose (Alces alces) overlaps with the food-scarce period in winter. During this period, moose deal with the limited forage resources available through hypometabolism with decreased heart rate and body temperature (T b ). Body temperature is also an indicator of oestrus, pregnancy and parturition, which is well documented in several domestic species. In this study, we sought to determine if moose displayed a similar T b pattern during pregnancy and parturition to domesticated ruminants, and if we could detect parturition by combining T b and activity data. We studied the T b pattern of 30 free-ranging adult female moose (≥1.5 years old), equipped with ruminal temperature loggers and GPS collars. We documented a 0.13-0.19°C higher T b in pregnant compared to non-pregnant moose, depending on the study area with the T b difference increasing along a south-north gradient, and a drop in T b and in activity when parturition was imminent. Detection of parturition was highly successful when combining T b and activity data with an accuracy of 91.5%. Our findings demonstrate that T b responses to pregnancy and parturition in a wild capital-breeding ruminant are similar to those of domesticated ruminants., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Optimal management of hunted species requires an understanding of the impacts of hunting on both individual animal and population levels. Recent technological advancements in biologging enable us to obtain increasingly detailed information from free-ranging animals, covering longer periods of time, and providing the data needed to assess such impacts. In Sweden, more than 80 000 moose are harvested annually, mostly hunted with the use of baying dogs. The effects of this hunting method on animal welfare and stress are understudied. Here, we evaluated 6 real and 17 experimental hunting approaches with baying dogs [wearing global positioning system (GPS) collars] on 8 adult female moose equipped with ruminal temperature loggers, subcutaneous heart rate (HR) loggers and GPS collars with accelerometers. The obtained data were used to analyse the behavioural and physiological responses of moose to hunting with dogs. Successful experimental approaches (moose and dog were within 240 m for >10 min) resulted in higher maximum body temperature (T b, 0.88°C higher) and a mean increase in HR of 24 bpm in moose at the day of the approach compared to the day after. The moose rested on average >90 min longer the day after the approach compared to the day of the approach. The moose travelled on average 4.2 km longer and had a 1.3 m/s higher maximum speed the day of the approach compared to the day after. Our results demonstrate that hunting with dogs increase moose energy expenditure and resting time (and consequently decrease time available for foraging) on an individual level. This could possibly affect body condition and reproduction rates if the hunting disturbances occur frequently., (© The Author(s) 2020. Published by Oxford University Press and the Society for Experimental Biology.)

In northern environments, the period of access to high-quality forage is limited, exerting strong selective pressure to optimize the timing of parturition. We analysed timing and variation in moose ( Alces alces ) parturition dates of 555 females at 18 study sites across 12° of latitude (56-68° N, 1350 km) in Sweden. We found evidence for a spatial match of parturition timing to vegetation onset, but no evidence that moose adjust parturition to vegetation onset in a given year. We found a breakpoint at 64° N. Despite adaptation across latitudes, temporal divergences occurred. Females below 64° N calved after vegetation onset and females above 64° N calved before. Here, parturition before vegetation onset might be a strategy to optimize forage utilization time with the very short growing season. Highly seasonal environments such as at higher latitudes may make it advantageous to adapt parturition towards long-term climatic patterns by matching the most favourable period. Given the direction of temporal divergence, our study suggests that climate change may have less of an impact on moose parturition at northern latitudes than southern latitudes.

Purpose: Three-dimensional (3D) printing allows for the fabrication of medical devices with complex geometries, such as soft actuators and robots that can be used in image-guided interventions. This study investigates flexible and rigid 3D-printing materials in terms of their impact on multimodal medical imaging., Methods: The generation of artifacts in clinical computer tomography (CT) and magnetic resonance (MR) imaging was evaluated for six flexible and three rigid materials, each with a cubical and a cylindrical geometry, and for one exemplary flexible fluidic actuator. Additionally, CT Hounsfield units (HU) were quantified for various parameter sets iterating peak voltage, x-ray tube current, slice thickness, and convolution kernel., Results: We found the image artifacts caused by the materials to be negligible in both CT and MR images. The HU values mainly depended on the elemental composition of the materials and applied peak voltage was ranging between 80 and 140 kVp. Flexible, nonsilicone-based materials were ranged between 51 and 114 HU. The voltage dependency was less than 29 HU. Flexible, silicone-based materials were ranged between 60 and 365 HU. The voltage-dependent influence was as large as 172 HU. Rigid materials ranged between -69 and 132 HU. The voltage-dependent influence was <33 HU., Conclusions: All tested materials may be employed for devices placed in the field of view during CT and MR imaging as no significant artifacts were measured. Moreover, the material selection in CT could be based on the desired visibility of the material depending on the application. Given the wide availability of the tested materials, we expect our results to have a positive impact on the development of devices and robots for image-guided interventions., (© 2019 American Association of Physicists in Medicine.)

Postmortem body temperature is used to estimate time of death in humans, but the available models are not validated for most nonhuman species. Here, we report that cooling in an adult female moose ( Alces alces ) equipped with a rumen temperature monitor was extremely slow, with a rumen temperature of 27-28 C as late as 40 h postmortem.

Objectives: To assess the risks for implant users with copper-containing intrauterine devices (IUDs) during MR and CT examinations., Methods: A tissue-mimicking phantom suitable for all experiments within this study was developed. Seven different types of copper IUDs were evaluated. Heating and dislocation of each IUD were investigated at two clinically relevant positions in 1.5 T and 3 T MR scanners. Artifacts in the field of view caused by each tested IUD were determined for clinical MR and CT imaging., Results: No significant heating of any tested IUD was detected during MR measurements. The temperature increase was less than 0.6 K for all IUDs. Neither angular deflection nor translation of any IUD was detected. Artifacts in MR images were limited to the very vicinity of the IUDs except for one IUD containing a steel-visualizing element. Streaking artifacts in CT were severe (up to 75.5%) in the slices including the IUD., Conclusion: No significant risk possibly harming the patient was determined during this phantom study, deeming MR examinations safe for women with an implanted copper IUD. Image quality was more impaired for CT than for MR imaging and needs careful consideration during diagnosis., Key Points: • Risk assessment of copper-containing IUDs with regard to heating, dislocation, and artifacts during MR and CT imaging. • Neither significant heating nor dislocation was determined in MR; image quality was more impaired for CT than for MR imaging and needs careful consideration during diagnosis. • The tested IUDs pose no additional risks for implant users during MR and CT examinations.

This work demonstrates a new method for the generation of mechanical shear wave during magnetic resonance elastography (MRE) that creates greater forces at higher vibrational frequencies as opposed to conventionally used pneumatic transducers. We developed an MR-compatible pneumatic turbine with an eccentric mass that creates a sinusoidal centrifugal force. The turbine was assessed with respect to its technical parameters and evaluated for MRE on a custom-made anthropomorphic prostate phantom. The silicone-based tissue-mimicking materials of the phantom were selected with regard to their complex shear moduli examined by rheometric testing. The tissue-mimicking materials closely matched human soft tissue elasticity values with a complex shear modulus ranging from 3.21 kPa to 7.29 kPa. We acquired MRE images on this phantom at 3 T with actuation frequencies of 50, 60 Hz, 70 Hz, and 80 Hz. The turbine generated vibrational wave amplitudes sufficiently large to entirely penetrate the phantoms during the feasibility study. Increased wave length in the stiffer inclusions compared to softer background material were detected. Our initial results suggest that silicone-based phantoms are useful for the evaluation of elasticities during MRE. Furthermore, our turbine seems suitable for the mechanical assessment of soft tissue during MRE., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Sodium magnetic resonance (MR) imaging provides noninvasive insights to cellular processes by measuring tissue sodium concentration (TSC). Many clinical studies combine sodium MR imaging with clinical standard MR procedures, in which contrast media is frequently administered. This work investigates the influence of gadolinium-based contrast agents on quantification of TSC. Thus, either scan pauses between early and late contrast-enhanced acquisitions can be used efficiently or sodium imaging can be performed as the final scan after dynamic contrast-enhanced acquisition., Materials and Methods: For this study, 2 gadolinium-based contrast agents, Dotarem and Gadovist, were diluted with saline solution covering contrast agent concentrations in a clinical range. In addition, agarose-based sample series were created to simulate tissue relaxation time behavior. In vivo, the influence of Dotarem on sodium acquisition and TSC quantification was investigated in 1 ischemic stroke patient., Results: Proton relaxation times decreased for increasing contrast agent concentrations as hyperbolic functions. Sodium relaxation times displayed a negative slope in regression analysis in most cases. The largest influence (-1.52 milliseconds per mmol/L contrast agent) was measured for sodium T1. Worst case calculations in ultrashort echo time sequence signal analysis showed a signal drop of (1.21% ± 0.56%) on tissue sodium quantification. In vivo sodium brain acquisitions of a stroke patient before and after Dotarem injection resulted in statistically nonsignificant differences in TSC quantification of relevant tissues and stroke areas (P > 0.05)., Conclusions: Our study showed a quantitative influence of Dotarem and Gadovist on sodium relaxation times. However, quantification of TSC was not impaired, which was proven by worst case calculations and nonsignificant differences in vivo in an ischemic stroke patient. We suggest performing sodium imaging in useful clinical positions in protocols regardless of included Dotarem or Gadovist administrations. Being flexible in the study protocol design will strengthen ongoing sodium imaging investigations for various pathologies.

In this work, the two compartment exchange model and two compartment uptake model were applied to obtain quantitative perfusion parameters in rectum carcinoma and the results were compared to those obtained by the deconvolution algorithm. Eighteen patients with newly diagnosed rectal carcinoma underwent 3 T MRI of the pelvis including a T 1 weighted dynamic contrastenhanced (DCE) protocol before treatment. Mean values for Plasma Flow (PF), Plasma Volume (PV) and Mean Transit Time (MTT) were obtained for all three approaches and visualized in parameter cards. For the two compartment models, Akaike Information Criterion (AIC) and [Formula: see text] were calculated. Perfusion parameters determined with the compartment models show results in accordance with previous studies focusing on rectal cancer DCE-CT (PF 2CX  = 68 ± 44 ml/100 ml/min, PF 2CU  = 55 ± 36 ml/100 ml/min) with similar fit quality (AIC:169 ± 81/179 ± 77, [Formula: see text]:10 ± 12/9 ± 10). Values for PF are overestimated whereas PV and MTT are underestimated compared to results of the deconvolution algorithm. Significant differences were found among all models for perfusion parameters as well as between the AIC and [Formula: see text] values. Quantitative perfusion parameters are dependent on the chosen tracer kinetic model. According to the obtained parameters, all approaches seem capable of providing quantitative perfusion values in DCE-MRI of rectal cancer.

Magnetic resonance elastography (MRE) is a technique for the quantification of tissue stiffness during MR examinations. It requires consistent methods for mechanical shear wave induction to the region of interest in the human body to reliably quantify elastic properties of soft tissues. This work proposes a novel 3D-printed mechanical actuator using the principle of centrifugal force for wave induction. The driver consists of a 3D-printed turbine vibrator powered by compressed air (located inside the scanner room) and an active driver controlling the pressure of inflowing air (placed outside the scanner room). The generated force of the proposed actuator increases for higher actuation frequencies as opposed to conventionally used air cushions. There, the displacement amplitude decreases with increasing actuation frequency resulting in a smaller signal-to-noise ratio. An initial phantom study is presented which demonstrates the feasibility of the actuator for MRE. The wave-actuation frequency was regulated in a range between 15 Hz and 60 Hz for force measurements and proved sufficiently stable (± 0.3 Hz) for any given nominal frequency. The generated forces depend on the weight of the eccentric unbalance within the turbine and ranged between 0.67 N to 2.70 N (for 15 Hz) and 3.09 N to 7.77 N (for 60 Hz). Therefore, the generated force of the presented actuator increases with rotational speed of the turbine and offers an elegant solution for sufficiently large wave actuation at higher frequencies. In future work, we will investigate an optimal ratio of the weight of unbalance to the size of turbine for appropriately large but tolerable wave actuation for a given nominal frequency.

Objectives: This work proposes a modular, anthropomorphic MR and CT thorax phantom that enables the comparison of experimental studies for quantitative evaluation of deformable, multimodal image registration algorithms and realistic multi-nuclear MR imaging techniques., Methods: A human thorax phantom was developed with insertable modules representing lung, liver, ribs and additional tracking spheres. The quality of human tissue mimicking characteristics was evaluated for 1 H and 23 Na MR as well as CT imaging. The position of landmarks in the lung lobes was tracked during CT image acquisition at several positions during breathing cycles. 1 H MR measurements of the liver were repeated after seven months to determine long term stability., Results: The modules possess HU, T 1 and T 2 values comparable to human tissues (lung module: -756±148HU, artificial ribs: 218±56HU (low CaCO 3 concentration) and 339±121 (high CaCO 3 concentration), liver module: T 1 =790±28ms, T 2 =65±1ms). Motion analysis showed that the landmarks in the lung lobes follow a 3D trajectory similar to human breathing motion. The tracking spheres are well detectable in both CT and MRI. The parameters of the tracking spheres can be adjusted in the following ranges to result in a distinct signal: HU values from 150 to 900HU, T 1 relaxation time from 550ms to 2000ms, T 2 relaxation time from 40ms to 200ms., Conclusion: The presented anthropomorphic multimodal thorax phantom fulfills the demands of a simple, inexpensive system with interchangeable components. In future, the modular design allows for complementing the present set up with additional modules focusing on specific research targets such as perfusion studies, 23 Na MR quantification experiments and an increasing level of complexity for motion studies., (Copyright © 2016. Published by Elsevier GmbH.)

Collisions with wild ungulates are an increasing traffic safety issue in boreal regions. Crashes involving smaller-bodied deer species usually lead to vehicle damage only, whereas collisions with a large animal, such as the moose, increase the risk of personal injuries. It is therefore important to understand both the factors affecting the number of moose-vehicle collisions (MVCs) and the underlying causes that turn an MVC into an accident involving personal injuries or fatalities. As a basis for temporal mitigation measures, we examined the annual and monthly variation of MVCs with and without personal injuries. Using a 22-year-long (1990-2011) time series from Finland, we tested the effect of moose population density and traffic volume on the yearly number of all MVCs and those leading to personal injuries. We also examined the monthly distribution of MVCs with and without personal injuries, and contrasted the Finnish findings with collision data from Sweden (years 2008-2010) and Norway (years 2008-2011). Both moose population abundance indices and traffic volume were positively related to the yearly variation in the number of MVCs in Finland. The proportion of MVCs involving personal injuries decreased during our 22-year study period. The monthly distribution of all MVCs peaked during the autumn or winter depending on country, while MVCs involving personal injury peaked in summer. Our study indicates that efforts to reduce MVCs involving personal injuries need to address driver awareness and attitudes during summer, despite most MVCs occurring in autumn or winter., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Animal movement patterns in space and time are a central aspect of animal ecology. Remotely-sensed environmental indices can play a key role in understanding movement patterns by providing contiguous, relatively fine-scale data that link animal movements to their environment. Still, implementation of newly available remotely-sensed data is often delayed in studies of animal movement, calling for a better flow of information to researchers less familiar with remotely-sensed data applications. Here, we reviewed the application of remotely-sensed environmental indices to infer movement patterns of animals in terrestrial systems in studies published between 2002 and 2013. Next, we introduced newly available remotely-sensed products, and discussed their opportunities for animal movement studies. Studies of coarse-scale movement mostly relied on satellite data representing plant phenology or climate and weather. Studies of small-scale movement frequently used land cover data based on Landsat imagery or aerial photographs. Greater documentation of the type and resolution of remotely-sensed products in ecological movement studies would enhance their usefulness. Recent advancements in remote sensing technology improve assessments of temporal dynamics of landscapes and the three-dimensional structures of habitats, enabling near real-time environmental assessment. Online movement databases that now integrate remotely-sensed data facilitate access to remotely-sensed products for movement ecologists. We recommend that animal movement studies incorporate remotely-sensed products that provide time series of environmental response variables. This would facilitate wildlife management and conservation efforts, as well as the predictive ability of movement analyses. Closer collaboration between ecologists and remote sensing experts could considerably alleviate the implementation gap. Ecologists should not expect that indices derived from remotely-sensed data will be directly analogous to field-collected data and need to critically consider which remotely-sensed product is best suited for a given analysis.

Background: Unlike metastatic colorectal cancer (CRC) there are to date few reports concerning the predictive value of molecular biomarkers on the clinical outcome in stage II/III CRC patients receiving adjuvant chemotherapy. Aim of this study was to assess the predictive value of proteins related with the EGFR- and VEGFR- signalling cascades in these patients., Methods: The patients' data examined in this study were from the collective of the 5-FU/FA versus 5-FU/FA/irinotecan phase III FOGT-4 trial. Tumor tissues were stained by immunohistochemistry for VEGF-C, VEGF-D, VEGFR-3, Hif-1 α, PTEN, AREG and EREG expression and evaluated by two independent, blinded investigators., Results: Patients with negative AREG and EREG expression on their tumor had a significant longer DFS in comparison to AREG/EREG positive ones (p< 0.05). The benefit on DFS in AREG-/EREG- patients was even stronger in the group that received 5-FU/FA/irinotecan as adjuvant treatment (p=0.002). Patients with strong expression of PTEN profited more in terms of OS under adjuvant treatment containing irinotecan (p< 0.05). Regarding markers of the VEGFR- pathway we found no correlation of VEGF-C- and VEGFR-3 expression with clinical outcome. Patients with negative VEGF-D expression had a trend to live longer when treated with 5-FU/FA (p=0.106). Patients who were negative for Hif-1 α, were disease-free in more than 50% at the end of the study and showed significant longer DFS-rates than those positive for Hif-1 α (p=0.007). This benefit was even stronger at the group treated with 5-FU/FA/irinotecan (p=0.026). Finally, AREG-/EREG-/PTEN+ patients showed a trend to live longer under combined treatment combination., Conclusions: The addition of irinotecan to adjuvant treatment with 5-FU/FA does not provide OS or DFS benefit in patients with stage II/III CRC. Nevertheless, AREG/EREG negative, PTEN positive and Hif-1 α negative patients might profit significantly in terms of DFS from a treatment containing fluoropyrimidines and irinotecan. Our results suggest a predictive value of these biomarkers concerning adjuvant chemotherapy with 5-FU/FA +/- irinotecan in stage II/III colorectal cancer.