Riku Klén - Academia.edu (original) (raw)

Papers by Riku Klén

npj Digital Medicine

Consumer wearables and sensors are a rich source of data about patients’ daily disease and sympto... more Consumer wearables and sensors are a rich source of data about patients’ daily disease and symptom burden, particularly in the case of movement disorders like Parkinson’s disease (PD). However, interpreting these complex data into so-called digital biomarkers requires complicated analytical approaches, and validating these biomarkers requires sufficient data and unbiased evaluation methods. Here we describe the use of crowdsourcing to specifically evaluate and benchmark features derived from accelerometer and gyroscope data in two different datasets to predict the presence of PD and severity of three PD symptoms: tremor, dyskinesia, and bradykinesia. Forty teams from around the world submitted features, and achieved drastically improved predictive performance for PD status (best AUROC = 0.87), as well as tremor- (best AUPR = 0.75), dyskinesia- (best AUPR = 0.48) and bradykinesia-severity (best AUPR = 0.95).

SSRN Electronic Journal

Summary: Background More contagious SARS-CoV-2 virus variants, breakthrough infections, waning im... more Summary: Background More contagious SARS-CoV-2 virus variants, breakthrough infections, waning immunity, and differential access to COVID-19 vaccines account for the worst yet numbers of hospitalization and deaths during the COVID-19 pandemic, particularly in resource-limited countries. There is an urgent need for clinically valuable, generalizable, and parsimonious triage tools assisting the appropriate allocation of hospital resources during the pandemic. We aimed to develop and extensively validate a machine learning-based tool for accurately predicting the clinical outcome of hospitalized COVID-19 patients. Methods: CODOP was built using modified stable iterative variable selection and linear regression with lasso regularisation. To avoid generalization problems, CODOP was trained and tested with three time-sliced and geographically distinct cohorts encompassing 40 511 blood-based analyses of COVID-19 patients from more than 110 hospitals in Spain and the USA during 2020-21. We assessed the discriminative ability of the model using the Area Under the Receiving Operative Curve (AUROC) as well as horizon and Kaplan-Meier risk stratification analyses. To reckon the fluctuating pressure levels in hospitals through the pandemic, we offer two online CODOP calculators suited for undertriage or overtriage scenarios. We challenged their generalizability and clinical utility throughout an evaluation with datasets gathered in five hospitals from three Latin American countries. Findings: CODOP uses 12 clinical parameters commonly measured at hospital admission and associated with the pathophysiology of COVID-19. CODOP reaches high discriminative ability up to nine days before clinical resolution (AUROC: 0.90-0.96, 95% CI 0.879-0.970), it is well calibrated, and it enables an effective dynamic risk stratification during hospitalization. The two CODOP online calculators predicted the clinical outcome of the majority of patients (73-100% sensitivity and 84-100% specificity) from the distinctive Latin American evaluation cohort. Interpretation: The high predictive performance of CODOP in geographically disperse patient cohorts and the easiness-of-use, strongly suggest its clinical utility as a global triage tool, particularly in resource-limited countries.

Journal of Nuclear Cardiology

Background Dual-gating reduces respiratory and cardiac motion effects but increases noise. With m... more Background Dual-gating reduces respiratory and cardiac motion effects but increases noise. With motion correction, motion is minimized and image quality preserved. We applied motion correction to create end-diastolic respiratory motion corrected images from dual-gated images. Methods [18F]-fluorodeoxyglucose ([18F]-FDG) PET images of 13 subjects were reconstructed with 4 methods: non-gated, dual-gated, motion corrected, and motion corrected with 4D-CT (MoCo-4D). Image quality was evaluated using standardized uptake values, contrast ratio, signal-to-noise ratio, coefficient of variation, and contrast-to-noise ratio. Motion minimization was evaluated using myocardial wall thickness. Results MoCo-4D showed improvement for contrast ratio (2.83 vs 2.76), signal-to-noise ratio (27.5 vs 20.3) and contrast-to-noise ratio (14.5 vs 11.1) compared to dual-gating. The uptake difference between MoCo-4D and non-gated images was non-significant (P > .05) for the myocardium (2.06 vs 2.15 g/mL), ...

EJNMMI Research

Background We investigated the image quality of 11C, 68Ga, 18F and 89Zr, which have different pos... more Background We investigated the image quality of 11C, 68Ga, 18F and 89Zr, which have different positron fractions, physical half-lifes and positron ranges. Three small animal positron emission tomography/computed tomography (PET/CT) systems were used in the evaluation, including the Siemens Inveon, RAYCAN X5 and Molecubes β-cube. The evaluation was performed on a single scanner level using the national electrical manufacturers association (NEMA) image quality phantom and analysis protocol. Acquisitions were performed with the standard NEMA protocol for 18F and using a radionuclide-specific acquisition time for 11C, 68Ga and 89Zr. Images were assessed using percent recovery coefficient (%RC), percentage standard deviation (%STD), image uniformity (%SD), spill-over ratio (SOR) and evaluation of image quantification. Results 68Ga had the lowest %RC ( 85%) and lowest %STD for the 5 mm rod across all systems. For 11C and 89Zr, the maximum %RC was close (> 76%) to the %RC with 18F. A la...

Journal d'Analyse Mathématique

For a self mapping f : D → D of the unit disk in C which has finite distortion, we give a separat... more For a self mapping f : D → D of the unit disk in C which has finite distortion, we give a separation condition on the components of the set where the distortion is large-say greater than a given constant-which implies that f extends homeomorphically and quasisymetrically to the boundary S and thus f shares its boundary values with a quasiconformal mapping whose distortion can be explicitly estimated in terms of the data. This result holds more generally. This condition, uniformly separated in modulus, allows the set where the distortion is large to accumulate densely on the boundary but does not allow a component to run out to the boundary. The lift of a Jordan domain in a Riemann surface to its universal cover D is always uniformly separated in modulus and this allows us to apply these results in the theory of Riemann surfaces to identify an interesting link between the support of the high distortion of a map and topology of the surface-again with explicit and good estimates. As part of our investigations we study mappings ϕ : S → S which are the germs of a conformal mapping and give good bounds on the distortion of a quasiconformal extension of ϕ. We extend these results to the germs of quasisymmetric mappings. These appear of independent interest and identify new geometric invariants.

Diagnostics

Magnetic resonance imaging-only radiotherapy treatment planning (MRI-only RTP) and positron emiss... more Magnetic resonance imaging-only radiotherapy treatment planning (MRI-only RTP) and positron emission tomography (PET)–MRI imaging require generation of synthetic computed tomography (sCT) images from MRI images. In this study, initial dosimetric evaluation was performed for a previously developed MRI-based attenuation correction (MRAC) method for use in MRI-only RTP of the brain. MRAC-based sCT images were retrospectively generated from Dixon MR images of 20 patients who had previously received external beam radiation therapy (EBRT). Bone segmentation performance and Dice similarity coefficient of the sCT conversion method were evaluated for bone volumes on CT images. Dose calculation accuracy was assessed by recalculating the CT-based EBRT plans using the sCT images as the base attenuation data. Dose comparison was done for the sCT- and CT-based EBRT plans in planning target volume (PTV) and organs at risk (OAR). Parametric dose comparison showed mean relative differences of <0....

Springer Monographs in Mathematics

Scientific Reports

Machine learning methods have gained increased popularity in biomedical research during the recen... more Machine learning methods have gained increased popularity in biomedical research during the recent years. However, very few of them support the analysis of longitudinal data, where several samples are collected from an individual over time. Additionally, most of the available longitudinal machine learning methods assume that the measurements are aligned in time, which is often not the case in real data. Here, we introduce a robust longitudinal machine learning method, named likelihood contrasts (LC), which supports study designs with unaligned time points. Our LC method is a binary classifier, which uses linear mixed models for modelling and log-likelihood for decision making. To demonstrate the benefits of our approach, we compared it with existing methods in four simulated and three real data sets. In each simulated data set, LC was the most accurate method, while the real data sets further supported the robust performance of the method. LC is also computationally efficient and ea...

Mobile health, the collection of data using wearables and sensors, is a rapidly growing field in ... more Mobile health, the collection of data using wearables and sensors, is a rapidly growing field in health research with many applications. Deriving validated measures of disease and severity that can be used clinically or as outcome measures in clinical trials, referred to as digital biomarkers, has proven difficult. In part due to the complicated analytical approaches necessary to develop these metrics. Here we describe the use of crowdsourcing to specifically evaluate and benchmark features derived from accelerometer and gyroscope data in two different datasets to predict the presence of Parkinson’s Disease (PD) and severity of three PD symptoms: tremor, dyskinesia and bradykinesia. 40 teams from around the world submitted features, and achieved drastically improved predictive performance for PD (best AUROC=0.87), as well as severity of tremor (best AUPR=0.75), dyskinesia (best AUPR=0.48) and bradykinesia (best AUPR=0.95).

Bladder Cancer

PURPOSE: Neoadjuvant chemotherapy (NAC) improves survival in muscle invasive bladder cancer (MIBC... more PURPOSE: Neoadjuvant chemotherapy (NAC) improves survival in muscle invasive bladder cancer (MIBC). Rate of adverse events (AE) have been reported only in randomized clinical trials (RCT). Purpose was to evaluate incidence, type, and risk factors of AEs during NAC treatment in a population-based setting. MATERIAL AND METHODS: The Finnish national cystectomy database covering years 2008-2014 was utilized. NAC associated AEs were reported by Common Terminology Criteria for Adverse Events (CTCAE) v.5.0. AEs during NAC in five-tier severity scale was the outcome measure. Spearman correlation between AEs and 22 clinical variables were calculated. P-values were corrected for multiple testing by controlling false discovery rate (FDR) with Benjamini-Hochberg method. RESULTS: Thirty-one percent of MIBC patients were assigned to NAC. Final analysis included 229 NAC patients representing 30% of radical cystectomy (RC) population. Majority (88%) received cisplatin-gemcitabine. 105 patients (46%) had no AEs. 124 patients (54%) had 168 AEs in total. Severe events (CTCAE grade 3-5) were documented in 31% of patients and one (0.4%) died. In five patients (2.1%) RC was not performed due to the AE. Of the severe AEs, hematological were most common, followed with cardiac, vascular and urinary tract as most commonly affected organ systems. The number of chemotherapy cycles was the only variable significantly associated with AEs. Severe AEs occurred already during or after the first cycle of NAC leading to early termination. CONCLUSION: NAC is generally well tolerated, but poses a considerable risk for adverse events. This is the first study to evaluate AEs caused by NAC in real life scenario on population level.

Monatshefte für Mathematik

We study local convexity properties of the triangular ratio metric balls in proper subdomains of ... more We study local convexity properties of the triangular ratio metric balls in proper subdomains of the real coordinate space. We also study inclusion properties of the visual angle metric balls and related hyperbolic type metric balls in the complement of the origin and the upper half space.

Scandinavian Journal of Urology

Sensors

Dual cardiac and respiratory gating is a well-known technique for motion compensation in nuclear ... more Dual cardiac and respiratory gating is a well-known technique for motion compensation in nuclear medicine imaging. In this study, we present a new data fusion framework for dual cardiac and respiratory gating based on multidimensional microelectromechanical (MEMS) motion sensors. Our approach aims at robust estimation of the chest vibrations, that is, high-frequency precordial vibrations and low-frequency respiratory movements for prospective gating in positron emission tomography (PET), computed tomography (CT), and radiotherapy. Our sensing modality in the context of this paper is a single dual sensor unit, including accelerometer and gyroscope sensors to measure chest movements in three different orientations. Since accelerometer- and gyroscope-derived respiration signals represent the inclination of the chest, they are similar in morphology and have the same units. Therefore, we use principal component analysis (PCA) to combine them into a single signal. In contrast to this, the...

BMC Cancer

Background: Prognostic markers specific to a particular cancer type can assist in the evaluation ... more Background: Prognostic markers specific to a particular cancer type can assist in the evaluation of survival probability of patients and help clinicians to assess the available treatment modalities. Methods: Gene expression data was analyzed from three independent colon cancer microarray gene expression data sets (N = 1052). Survival analysis was performed for the three data sets, stratified by the expression level of the LINE-1 type transposase domain containing 1 (L1TD1). Correlation analysis was performed to investigate the role of the interactome of L1TD1 in colon cancer patients. Results: We found L1TD1 as a novel positive prognostic marker for colon cancer. Increased expression of L1TD1 associated with longer disease-free survival in all the three data sets. Our results were in contrast to a previous study on medulloblastoma, where high expression of L1TD1 was linked with poor prognosis. Notably, in medulloblastoma L1TD1 was co-expressed with its interaction partners, whereas our analysis revealed lack of co-expression of L1TD1 with its interaction partners in colon cancer. Conclusions: Our results identify increased expression of L1TD1 as a prognostic marker predicting longer disease-free survival in colon cancer patients.

Nature communications, Oct 24, 2018

The response to respiratory viruses varies substantially between individuals, and there are curre... more The response to respiratory viruses varies substantially between individuals, and there are currently no known molecular predictors from the early stages of infection. Here we conduct a community-based analysis to determine whether pre- or early post-exposure molecular factors could predict physiologic responses to viral exposure. Using peripheral blood gene expression profiles collected from healthy subjects prior to exposure to one of four respiratory viruses (H1N1, H3N2, Rhinovirus, and RSV), as well as up to 24 h following exposure, we find that it is possible to construct models predictive of symptomatic response using profiles even prior to viral exposure. Analysis of predictive gene features reveal little overlap among models; however, in aggregate, these genes are enriched for common pathways. Heme metabolism, the most significantly enriched pathway, is associated with a higher risk of developing symptoms following viral exposure. This study demonstrates that pre-exposure mo...

Journal of Mathematical Analysis and Applications

Quasiconformal homeomorphisms of the whole space R n , onto itself normalized at one or two point... more Quasiconformal homeomorphisms of the whole space R n , onto itself normalized at one or two points are studied. In particular, the case when the maximal dilatation tends to 1 is in the focus. Our main result provides a spatial analogue of a classical result due to Teichmüller. Unlike Teichmüller's result, our bounds are explicit. Explicit bounds are based on Bernoulli type inequalities and asymptotically sharp bounds for special functions involving complete elliptic integrals. Finally, we discuss the behavior of the quasihyperbolic metric under quasiconformal maps and prove a sharp result for quasiconformal maps of R n \ {0} onto itself.