| 1. |
- Schmitz, Alexander, et al.
(författare)
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Longitudinal minimal residual disease assessment in multiple myeloma patients in complete remission : results from the NMSG flow-MRD substudy within the EMN02/HO95 MM trial
- 2022
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Ingår i: BMC Cancer. - : BMC. - 1471-2407. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple myeloma remains an incurable disease with multiple relapses due to residual myeloma cells in the bone marrow of patients after therapy. Presence of small number of cancer cells in the body after cancer treatment, called minimal residual disease, has been shown to be prognostic for progression-free and overall survival. However, for multiple myeloma, it is unclear whether patients attaining minimal residual disease negativity may be candidates for treatment discontinuation. We investigated, if longitudinal flow cytometry-based monitoring of minimal residual disease (flow-MRD) may predict disease progression earlier and with higher sensitivity compared to biochemical assessments. Methods: Patients from the Nordic countries with newly diagnosed multiple myeloma enrolled in the European-Myeloma-Network-02/Hovon-95 (EMN02/HO95) trial and undergoing bone marrow aspiration confirmation of complete response, were eligible for this Nordic Myeloma Study Group (NMSG) substudy. Longitdudinal flow-MRD assessment of bone marrow samples was performed to identify and enumerate residual malignant plasma cells until observed clinical progression. Results: Minimal residual disease dynamics were compared to biochemically assessed changes in serum free light chain and M-component. Among 20 patients, reaching complete response or stringent complete response during the observation period, and with >= 3 sequential flow-MRD assessments analysed over time, increasing levels of minimal residual disease in the bone marrow were observed in six cases, preceding biochemically assessed disease and clinical progression by 5.5 months and 12.6 months (mean values), respectively. Mean malignant plasma cells doubling time for the six patients was 1.8 months (95% CI, 1.4-2.3 months). Minimal malignant plasma cells detection limit was 4 x 10-5. Conclusions: Flow-MRD is a sensitive method for longitudinal monitoring of minimal residual disease dynamics in multiple myeloma patients in complete response. Increasing minimal residual disease levels precedes biochemically assessed changes and is an early indicator of subsequent clinical progression.
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| 2. |
- Alifier, Marek, et al.
(författare)
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Cardiac Surgery is Associated with Biomarker Evidence of Neuronal Damage.
- 2020
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 74:4, s. 1211-1220
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Tidskriftsartikel (refereegranskat)abstract
- Anesthesia and surgery is commonly associated with central nervous system sequelae and cognitive symptoms, which may be caused by neuronal injury. Neuronal injury can be monitored by plasma concentrations of the neuronal biomarkers tau and neurofilament light protein (NFL). Currently, there are no studies examining whether neuronal injury varies between surgical procedures.Our aim was to investigate if neuronal damage is more frequent after cardiac than after otolaryngeal surgery, as estimated by tau and NFL concentrations in plasma.Blood samples were drawn before, during, and after surgery and concentrations of tau, NFL, Aβ40, and Aβ42 were measured in 25 patients undergoing cardiac surgery (9 off-pump and 16 on-pump) and 26 patients undergoing otolaryngeal surgery.Tau increased during surgery (1752%, p=0.0001) and NFL rose seven days post-surgery (1090%, p<0.0001) in patients undergoing cardiac surgery; even more in patients on-pump than off-pump. No changes were observed in patients undergoing otolaryngeal surgery and only minor fluctuations were observed for Aβ40 and Aβ42.Cardiac surgery is associated with neuronal injury, which is aggravated by extracorporeal circulation. Analyses of NFL and tau in blood may guide development of surgical procedures to minimize neuronal damage, and may also be used in longitudinal clinical studies to assess the relationship of surgery with future neurocognitive impairment or dementia.
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| 3. |
- Andreasson, Ulf, 1968, et al.
(författare)
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Assessing the commutability of candidate reference materials for the harmonization of neurofilament light measurements in blood
- 2023
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 61:7, s. 1245-1254
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Neurofilament light chain (NfL) concentration in blood is a biomarker of neuro-axonal injury in the nervous system and there now exist several assays with high enough sensitivity to measure NfL in serum and plasma. There is a need for harmonization with the goal of creating a certified reference material (CRM) for NfL and an early step in such an effort is to determine the best matrix for the CRM. This is done in a commutability study and here the results of the first one for NfL in blood is presented.Methods Forty paired individual serum and plasma samples were analyzed for NfL on four different analytical platforms. Neat and differently spiked serum and plasma were evaluated for their suitability as a CRM using the difference in bias approach.Results The correlation between the different platforms with regards to measured NfL concentrations were very high (Spearman's rho >= 0.96). Samples spiked with cerebrospinal fluid (CSF) showed higher commutability compared to samples spiked with recombinant human NfL protein and serum seems to be a better choice than plasma as the matrix for a CRM.Conclusions The results from this first commutability study on NfL in serum/plasma showed that it is feasible to create a CRM for NfL in blood and that spiking should be done using CSF rather than with recombinant human NfL protein.
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| 4. |
- Andreasson, Ulf, 1968, et al.
(författare)
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Method and Clinical Validation of Biomarkers for Neurodegenerative Diseases
- 2021
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Ingår i: Cerebrospinal Fluid Biomarkers. Neuromethods, vol 168. Teunissen C.E., Zetterberg H. (eds). - New York, NY : Springer. - 0893-2336. - 9781071613184 ; , s. 163-173
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- In the Merriam-Webster dictionary, one definition of the word valid is “well-grounded or justifiable: being at once relevant and meaningful.” Validation is then the process of determining the degree of validity. From this broad definition, it follows that validations can be made in many different fields with quite different implications. When talking about validation, it is therefore important to specify the subject under scrutiny and in this chapter the focus will be on validation of biomarkers. © 2021, Springer Science+Business Media, LLC, part of Springer Nature.
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| 5. |
- Arvidsson Rådestig, Maya, et al.
(författare)
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Cerebrospinal fluid biomarkers of axonal and synaptic degeneration in a population-based sample
- 2023
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Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundNeurofilament light (NfL) and neurogranin (Ng) are promising candidate AD biomarkers, reflecting axonal and synaptic damage, respectively. Since there is a need to understand the synaptic and axonal damage in preclinical Alzheimer's disease (AD), we aimed to determine the cerebrospinal fluid (CSF) levels of NfL and Ng in cognitively unimpaired elderly from the Gothenburg H70 Birth Cohort Studies classified according to the amyloid/tau/neurodegeneration (A/T/N) system.MethodsThe sample consisted of 258 cognitively unimpaired older adults (age 70, 129 women and 129 men) from the Gothenburg Birth Cohort Studies. We compared CSF NfL and Ng concentrations in A/T/N groups using Student's T-test and ANCOVA.ResultsCSF NfL concentration was higher in the A-T-N+ group (p=0.001) and the A-T+N+ group (p=0.006) compared with A-T-N-. CSF Ng concentration was higher in the A-T-N+, A-T+N+, A+T-N+, and A+T+N+ groups (p<0.0001) compared with A-T-N-. We found no difference in NfL or Ng concentration in A+ compared with A- (disregarding T- and N- status), whereas those with N+ had higher concentrations of NfL and Ng compared with N- (p<0.0001) (disregarding A- and T- status).ConclusionsCSF NfL and Ng concentrations are increased in cognitively normal older adults with biomarker evidence of tau pathology and neurodegeneration.
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| 6. |
- Borngrund, Carl, 1992-, et al.
(författare)
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Automating the Short-Loading Cycle: Survey and Integration Framework
- 2024
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Ingår i: Applied Sciences. - : MDPI. - 2076-3417. ; 14:11
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Tidskriftsartikel (refereegranskat)abstract
- The short-loading cycle is a construction task where a wheel loader scoops material from a nearby pile in order to move that material to the tipping body of a dump truck. The short-loading cycle is a vital task performed in high quantities and is often part of a more extensive never-ending process to move material for further refinement. This, together with the highly repetitive nature of the short-loading cycle, makes it a suitable candidate for automation. However, the short-loading cycle is a complex task where the mechanics of the wheel loader together with the interaction between the wheel loader and the environment needs to be considered. This must be achieved while maintaining some productivity goal and, concurrently, minimizing the used energy. The main objective of this work is to analyze the short-loading cycle, assess the current state of research in this field, and discuss the steps required to progress towards a minimal viable product consisting of individual automation solutions that can perform the short-loading cycle well enough to be used by early adopters. This is achieved through a comprehensive literature study and consequent analysis of the review results. From this analysis, the requirements of an MVP are defined and some gaps which are currently hindering the realization of the MVP are presented.
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| 7. |
- Borngrund, Carl, 1992-
(författare)
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Automation of Navigation During the Short-loading Cycle Using Machine Vision
- 2022
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Earth-moving machines are machines used in a wide range of industries, such as the construction industry, to perform tasks related to earthworks.Currently, the vast majority of earth-moving machines are human-operated where expert operators perform these industry vital tasks.One such task is the short-loading cycle which is a repetitive work cycle performed in high quantities within the construction industry.This work cycle aims to use a wheel-loader to move material from a pile or from the ground to the tipping body of a dump truck.Not only is this task repetitive and performed in high quantities, but it is also representative of the knowledge required to perform a wide set of other work cycles, hence a good candidate for automation.Skilled operators use their sensory input to perform the tasks required, such as tactile, sound and sight.One of the most important senses leveraged during normal operations is sight, as it is used to locate dynamic objects and detect dangers.Thus to be able to replace the driver of an earth-moving machine with an autonomous system, the system requires similar vision capabilities.Machine Vision is a field where the goal is to use some type of vision sensor, such as cameras, to extract relevant high-level information from images or video streams.This thesis aims to examine how machine vision can be used within the short-loading cycle to facilitate performing said work cycle autonomously.The main findings in this thesis are threefold: Firstly, two knowledge gaps are identified in the domain of automation during the short-loading cycle.These relate to the loading of heterogeneous material and navigation during loading and unloading.Secondly, we show that it is possible to train a deep learning model to detect the cab, wheels and tipping body of a scale-model dump truck while mimicking the approach towards the load carrier during the short-loading cycle.This model can then be applied to real vehicles to detect the same objects, with no additional training.Lastly, we show that linear interpolation can be used to perform semi-automatic labelling of camera-based video data of the approach of a wheel-loader towards a dump truck during the short-loading cycle.This technique decreases the annotation workload by around 95% while retaining comparable performance.The future direction of this work includes using techniques such as reinforcement learning to teach a model to perform the navigation required during the short-loading cycle.Future work also includes using world models to learn representations of underlying structures in the environment, open-ended learning to transfer the learned knowledge to adjacent work cycles and using machine vision to find the point of attack for scooping heterogeneous material.
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| 8. |
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| 9. |
- Borngrund, Carl, 1992-
(författare)
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Towards Deep-learning-based Autonomous Navigation in the Short-loading Cycle
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Earth-moving machines, such as wheel loaders, are a type of heavy-duty machinery used within the construction industry to perform vital tasks, such as digging, transporting, and mining applications. One of these tasks is the short-loading cycle, where an operator manoeuvres the wheel loader to move material from a pile to the tipping body of a dump truck, through navigation, scooping, and dumping. The short-loading cycle is a repetitive task performed in high quantities, often as part of a larger refinement process, making it interesting for automation.The main objective of this thesis work is to investigate challenges facing the automation of the short-loading cycle, focusing in particular on subtasks that can be efficiently addressed with deep learning methods. A secondary objective is to examine how alternative development paths, such as scale models, or simulations, can be used to enable data-driven automation of the short-loading cycle, as directly experimenting on real vehicles has a high associated cost when large numbers of timesteps are needed to gather enough data.To investigate the two objectives, the literature is systematically reviewed to identify research gaps, challenges, and the usage of deep learning techniques. Secondly, a set of deep learning techniques is investigated to address perception and actuation problems identified as challenging and important for the automation of the short-loading cycle.The investigation of deep learning techniques involves training and validating a realtime object detector neural network to identify key components (wheels, tipping body, and cab) on a scale model dump truck while testing on a real vehicle. This resulted in a localisation and classification degradation of only 14% between the scale model and the real dump truck, with no additional training. In addition, an examination to minimize the annotation workload of humans found that it is possible to decrease the workload by 95% while still retaining similar detection performance by leveraging linear interpolation.Lastly, this thesis presents an investigation regarding the usage of reinforcement learning for navigation during the short-loading cycle. The results indicate that training the agent in simulation is currently required as the agent obtains the maximum reward after timesteps in the order of millions before being capable of performing the task. The results suggest that the trained agent is capable of bridging the gap between simulation and reality to complete a simplified version of the navigation task during the short-loading cycle.The experiments presented in this thesis provide proof of concept that indicates deep learning techniques can aid in the realisation of an autonomous solution. Moreover, the results show that development paths allowing for experiments providing large numbers of timesteps can facilitate the practical use of such techniques.
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| 10. |
- Boulo, S., et al.
(författare)
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First amyloid β1-42 certified reference material for re-calibrating commercial immunoassays
- 2020
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:11, s. 1493-1503
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Reference materials based on human cerebrospinal fluid were certified for the mass concentration of amyloid beta (Aβ)1-42 (Aβ42). They are intended to be used to calibrate diagnostic assays for Aβ42. Methods: The three certified reference materials (CRMs), ERM-DA480/IFCC, ERM-DA481/IFCC and ERM-DA482/IFCC, were prepared at three concentration levels and characterized using isotope dilution mass spectrometry methods. Roche, EUROIMMUN, and Fujirebio used the three CRMs to re-calibrate their immunoassays. Results: The certified Aβ42 mass concentrations in ERM-DA480/IFCC, ERM-DA481/IFCC, and ERM-DA482/IFCC are 0.45, 0.72, and 1.22μg/L, respectively, with expanded uncertainties (k=2) of 0.07, 0.11, and 0.18μg/L, respectively. Before re-calibration, a good correlation (Pearson's r>0.97), yet large biases, were observed between results from different commercial assays. After re-calibration the between-assay bias was reduced to<5%. Discussion: The Aβ42 CRMs can ensure the equivalence of results between methods and across platforms for the measurement of Aβ42. © 2020 the Alzheimer's Association
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