Reproducible radiomics through automated machine learning validated on twelve clinical applications

Radiomics uses quantitative medical imaging features to predict clinical outcomes. Currently, in a new clinical application, findingthe optimal radiomics method out of the wide range of available options has to be done manually through a heuristic trial-anderror process. In this study we propose a framework for automatically optimizing the construction of radiomics workflows perapplication. To this end, we formulate radiomics as a modular workflow and include a large collection of common algorithms foreach component. To optimize the workflow per application, we employ automated machine learning using a random search andensembling. We evaluate our method in twelve different clinical applications, resulting in the following area under the curves: 1)liposarcoma (0.83); 2) desmoid-type fibromatosis (0.82); 3) primary liver tumors (0.80); 4) gastrointestinal stromal tumors (0.77);5) colorectal liver metastases (0.61); 6) melanoma metastases (0.45); 7) hepatocellular carcinoma (0.75); 8) mesenteric fibrosis(0.80); 9) prostate cancer (0.72); 10) glioma (0.71); 11) Alzheimer’s disease (0.87); and 12) head and neck cancer (0.84). Weshow that our framework has a competitive performance compared human experts, outperforms a radiomics baseline, and performssimilar or superior to Bayesian optimization and more advanced ensemble approaches. Concluding, our method fully automaticallyoptimizes the construction of radiomics workflows, thereby streamlining the search for radiomics biomarkers in new applications.To facilitate reproducibility and future research, we publicly release six datasets, the software implementation of our framework,and the code to reproduce this study

Autonomy in participation in cerebral palsy from childhood to adulthood

Aim: To determine the long-term development of autonomy in participation of individuals with cerebral palsy (CP) without intellectual disability. Method: Individuals with CP (n=189, 117 males, 72 females; mean age [SD] 21y 11mo [4y 11mo], range 12–34y); were assessed cross-sectionally (46%) or up to four times (54%), between the ages of 12 and 34 years. Autonomy in participation was classified using phase 3 of the Rotterdam Transition Profile. A logistic generalized estimating equation regression model was used to analyse autonomy in six domains (independent variables: age, Gross Motor Function Classification System [GMFCS] level, and interaction between age and GMFCS level). Proportions of autonomy were compared to references using binomial tests (p<0.05). Results: In most domains, over 90% of participants (n=189, 400 observations, 80% in GMFCS levels I and II) reached autonomy in participation in their late twenties, except for intimate/sexual relationships. Those in GMFCS levels III to V compared to those in GMFCS levels I and II had less favourable development of autonomy in the transportation, intimate relationships, employment, and housing domains, and more favourable development in the finances domain. Compared to references, fewer individuals with CP were autonomous in participation. Interpretation: This knowledge of autonomy may guide the expectations of young people with CP and their caregivers. Furthermore, rehabilitation professionals should address autonomy development in intimate relationships, employment, and housing, especially in individuals with lower gross motor function. What this paper adds: Individuals with cerebral palsy without intellectual disability achieved autonomy in most participation domains. Regarding intimate relationships, they continued to have less experience compared to age-matched references. Development of autonomy was less favourable for individuals in Gross Motor Function Classification System levels III to V

Hamstring-and-lower-back flexibility in male amateur soccer players

Objective: This study investigated the hamstring-and-lower-back flexibility (HLBF) of male adult amateur soccer players, using the sit-and-reach test (SRT), with a view to obtaining population-based reference values and to determining whether SRT scores are associated with player characteristics. Design: Cross-sectional cohort study. Setting: Teams from high-level Dutch amateur soccer competitions were recruited for participation. Participants: Dutch male high-level amateur field soccer players (n = 449) of age 18 to 40 years. Players with a hamstring injury at the moment of SRT-measurement or any other injury that prevented them from following the SRT protocol were excluded. Main Outcome Measures: Sit-and-reach test scores were measured and then population-based reference values were calculated as follows: .2SD below mean (defining "very low" HLBF), 1SD-2SD below mean ("low" HLBF), 1SD below mean to 1SD above mean ("normal" HLBF), 1SD-2SD above mean ("high" HLBF), and .2SD above mean ("very high" HLBF). Whether SRT scores were correlated with player characteristics was determined using a Pearson correlation coefficient or Spearman rho. Results: Sit-and-reach test scores ranged from 0 to 43.5 cm (mean 22.0 cm, SD 9.2). The cutoff points for population-based reference values were ,3.5 cm for "very low", 3.5 to 13.0 cm for "low", 13.0 to 31.0 cm for "normal", 31.0 to 40.5 cm for "high", and .40.5 cm for "very high". Sit-and-reach test scores were significantly associated with players' height (r = 20.132, P = 0.005), body mass index (r = 0.114, P = 0.016), and history of anterior cruciate ligament surgery (P , 0.001). Conclusions: This study is the first to describe the HLBF of amateur soccer players. The SRT reference values with cutoff points may facilitate evidence-based decision making regarding HLBF, and the SRT might be a useful tool to assess injury risk, performance, or for diagnostic purposes

Hamstring-and-lower-back flexibility in male amateur soccer players

Objective: This study investigated the hamstring-and-lower-back flexibility (HLBF) of male adult amateur soccer players, using the sit-and-reach test (SRT), with a view to obtaining population-based reference values and to determining whether SRT scores are associated with player characteristics. Design: Cross-sectional cohort study. Setting: Teams from high-level Dutch amateur soccer competitions were recruited for participation. Participants: Dutch male high-level amateur field soccer players (n = 449) of age 18 to 40 years. Players with a hamstring injury at the moment of SRT-measurement or any other injury that prevented them from following the SRT protocol were excluded. Main Outcome Measures: Sit-and-reach test scores were measured and then population-based reference values were calculated as follows: .2SD below mean (defining "very low" HLBF), 1SD-2SD below mean ("low" HLBF), 1SD below mean to 1SD above mean ("normal" HLBF), 1SD-2SD above mean ("high" HLBF), and .2SD above mean ("very high" HLBF). Whether SRT scores were correlated with player characteristics was determined using a Pearson correlation coefficient or Spearman rho. Results: Sit-and-reach test scores ranged from 0 to 43.5 cm (mean 22.0 cm, SD 9.2). The cutoff points for population-based reference values were ,3.5 cm for "very low", 3.5 to 13.0 cm for "low", 13.0 to 31.0 cm for "normal", 31.0 to 40.5 cm for "high", and .40.5 cm for "very high". Sit-and-reach test scores were significantly associated with players' height (r = 20.132, P = 0.005), body mass index (r = 0.114, P = 0.016), and history of anterior cruciate ligament surgery (P , 0.001). Conclusions: This study is the first to describe the HLBF of amateur soccer players. The SRT reference values with cutoff points may facilitate evidence-based decision making regarding HLBF, and the SRT might be a useful tool to assess injury risk, performance, or for diagnostic purposes

Designing a tool to support patient and public involvement in research projects: the Involvement Matrix

Background: Interest in patient involvement in research is growing. Research should rather be 'with' or 'by' patients, and not only be 'about' or 'for' patients. Patients' active involvement in research is not self-evident and special efforts have to be made. If we make efforts towards patient involvement, it could contribute to even more relevant projects with an even greater impact. In this paper we describe the process of development of a tool to support patient involvement in research projects. Methods: The tool development was done in a co-creation of experience experts (patients and their parents/relatives) together with researchers. We used a participatory method in an iterative process comprising three consecutive stages. First, the purpose for the tool was explored, using focus groups. Second, the main ingredients and conceptualization for the tool were determined, using a narrative review. Third, the so-called Involvement Matrix was formalized and finalized using various expert panels. Results: A conversation tool was developed, through which researchers and patients could discuss and explain their roles of involvement in a research project. This tool was formalized and visualized as a 'matrix'. The so-called Involvement Matrix describes five roles (i.e., Listener, Co-thinker, Advisor, Partner, and Decision-maker) and three phases (i.e., Preparation, Execution, and Implementation) and includes a user's guide. Conclusion: The Involvement Matrix can be used prospectively to discuss about possible roles of patients in different phases of projects, and retrospectively to discuss whether roles were carried out satisfactorily. Sharing experiences with the Involvement Matrix and evaluating its impact are the next steps in supporting patient involvement in research

Fluorescent PCDTBT Nanoparticles with Tunable Size for Versatile Bioimaging

Conjugated polymer nanoparticles exhibit very interesting properties for use as bio-imaging agents. In this paper, we report the synthesis of PCDTBT (poly([9-(1&rsquo;-octylnonyl)-9H-carbazole-2,7-diyl]-2,5-thiophenediyl-2,1,3-benzothiadiazole-4,7-diyl-2,5-thiophene-diyl)) nanoparticles of varying sizes using the mini-emulsion and emulsion/solvent evaporation approach. The effect of the size of the particles on the optical properties is investigated using UV-Vis absorption and fluorescence emission spectroscopy. It is shown that PCDTBT nanoparticles have a fluorescence emission maximum around 710 nm, within the biological near-infrared &ldquo;optical window&rdquo;. The photoluminescence quantum yield shows a characteristic trend as a function of size. The particles are not cytotoxic and are taken up successfully by human lung cancer carcinoma A549 cells. Irrespective of the size, all particles show excellent fluorescent brightness for bioimaging. The fidelity of the particles as fluorescent probes to study particle dynamics in situ is shown as a proof of concept by performing raster image correlation spectroscopy. Combined, these results show that PCDTBT is an excellent candidate to serve as a fluorescent probe for near-infrared bio-imaging

The Preventive Effect of the Nordic Hamstring Exercise on Hamstring Injuries in Amateur Soccer Players : A Randomized Controlled Trial

Background: Hamstring injuries are the most common muscle injuries in soccer, and they have a high rate of recurrence. Eccentric hamstrings strength is recognized as an important modifiable risk factor. This led to the development of prevention exercises such as the nordic hamstring exercise (NHE). The effectiveness of the NHE on hamstring injury prevention has never been investigated in amateur soccer. Purpose: To investigate the preventive effect of the NHE on the incidence and severity of hamstring injuries in male amateur soccer players. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Male amateur soccer players (age, mean SD, 24.5 3.8 years) from 40 teams were randomly allocated to an intervention (n = 20 teams, 292 players) or control group (n = 20 teams, 287 players). The intervention group was instructed to perform 25 sessions of NHE in a 13-week period. Both the intervention and control groups performed regular soccer training and were followed for hamstring injury incidence and severity during the 2013 calendar year. At baseline, personal characteristics (eg, age, injury history, field position) were gathered from all participants via a questionnaire. Primary outcome was injury incidence. Secondary outcomes were injury severity and compliance with the intervention protocol. Results: A total of 38 hamstring injuries were recorded, affecting 36 of 579 players (6.2%). The overall injury incidence rate was 0.7 (95% CI, 0.6-0.8) per 1000 player hours, 0.33 (95% CI, 0.25-0.46) in training, and 1.2 (95% CI, 0.82-1.94) in matches. Injury incidence rates were significantly different between the intervention (0.25; 95% CI, 0.19-0.35) and control groups (0.8; 95% CI, 0.61-1.15), (2)(1, n = 579) = 7.865; P = .005. The risk for hamstring injuries was reduced in the intervention group compared with the control group (odds ratio, 0.282; 95% CI, 0.110-0.721) and was statistically significant (P = .005). No statistically significant differences were identified between the intervention and control groups regarding injury severity. Compliance with the intervention protocol was 91%. Conclusion: Incorporating the NHE protocol in regular amateur training significantly reduces hamstring injury incidence, but it does not reduce hamstring injury severity. Compliance with the intervention was excellent

The Preventive Effect of the Nordic Hamstring Exercise on Hamstring Injuries in Amateur Soccer Players : A Randomized Controlled Trial

Background: Hamstring injuries are the most common muscle injuries in soccer, and they have a high rate of recurrence. Eccentric hamstrings strength is recognized as an important modifiable risk factor. This led to the development of prevention exercises such as the nordic hamstring exercise (NHE). The effectiveness of the NHE on hamstring injury prevention has never been investigated in amateur soccer. Purpose: To investigate the preventive effect of the NHE on the incidence and severity of hamstring injuries in male amateur soccer players. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Male amateur soccer players (age, mean SD, 24.5 3.8 years) from 40 teams were randomly allocated to an intervention (n = 20 teams, 292 players) or control group (n = 20 teams, 287 players). The intervention group was instructed to perform 25 sessions of NHE in a 13-week period. Both the intervention and control groups performed regular soccer training and were followed for hamstring injury incidence and severity during the 2013 calendar year. At baseline, personal characteristics (eg, age, injury history, field position) were gathered from all participants via a questionnaire. Primary outcome was injury incidence. Secondary outcomes were injury severity and compliance with the intervention protocol. Results: A total of 38 hamstring injuries were recorded, affecting 36 of 579 players (6.2%). The overall injury incidence rate was 0.7 (95% CI, 0.6-0.8) per 1000 player hours, 0.33 (95% CI, 0.25-0.46) in training, and 1.2 (95% CI, 0.82-1.94) in matches. Injury incidence rates were significantly different between the intervention (0.25; 95% CI, 0.19-0.35) and control groups (0.8; 95% CI, 0.61-1.15), (2)(1, n = 579) = 7.865; P = .005. The risk for hamstring injuries was reduced in the intervention group compared with the control group (odds ratio, 0.282; 95% CI, 0.110-0.721) and was statistically significant (P = .005). No statistically significant differences were identified between the intervention and control groups regarding injury severity. Compliance with the intervention protocol was 91%. Conclusion: Incorporating the NHE protocol in regular amateur training significantly reduces hamstring injury incidence, but it does not reduce hamstring injury severity. Compliance with the intervention was excellent

Determinants of developmental gain in daily activities in young children with cerebral palsy

The aim of this study was to examine which child and family characteristics at the child's age of 2 years are determinants of development of self-care and mobility activities over a period of 2 years in young children with cerebral palsy (CP). Longitudinal data of 92 children, representing all levels of the Gross Motor Function Classification System (GMFCS), were analyzed. Children's self-care and mobility activities were assessed with the Functional Skills Scale of the Pediatric Evaluation of Disability Inventory. Development of self-care and mobility activities was related to several child determinants but no family determinants. GMFCS, type of CP, intellectual capacity, and epilepsy were related to the development of self-care and mobility activities, while manual ability and spasticity were related to development of mobility activities. Multivariate analysis indicated that GMFCS and intellectual capacity were the strongest determinants of development of self-care activities, and GMFCS was the strongest determinant of development of mobility activities. The change in self-care and mobility activities was less favorable in severely affected children with severe disability. Knowledge of GMFCS level and intellectual capacity is important in anticipating change over time and goal setting in young children with CP

Determinants of developmental gain in daily activities in young children with cerebral palsy

The aim of this study was to examine which child and family characteristics at the child's age of 2 years are determinants of development of self-care and mobility activities over a period of 2 years in young children with cerebral palsy (CP). Longitudinal data of 92 children, representing all levels of the Gross Motor Function Classification System (GMFCS), were analyzed. Children's self-care and mobility activities were assessed with the Functional Skills Scale of the Pediatric Evaluation of Disability Inventory. Development of self-care and mobility activities was related to several child determinants but no family determinants. GMFCS, type of CP, intellectual capacity, and epilepsy were related to the development of self-care and mobility activities, while manual ability and spasticity were related to development of mobility activities. Multivariate analysis indicated that GMFCS and intellectual capacity were the strongest determinants of development of self-care activities, and GMFCS was the strongest determinant of development of mobility activities. The change in self-care and mobility activities was less favorable in severely affected children with severe disability. Knowledge of GMFCS level and intellectual capacity is important in anticipating change over time and goal setting in young children with CP