Background:Accelerometer-based measures can provide valuable and objective information about arm and leg use in daily life. This information can be particularly useful in tailoring treatment and rehabilitation in people with disabling spasticity after stroke. To better understand clinical relevance of accelerometer-based measures, this study aimed to determine the strength of relationships between real-life arm and leg activity and a set of clinical assessments encompassing body function and activity domains. Methods:Thirty-five individuals with disabling spasticity in the chronic stage of stroke (mean age 56.8 ± 8.9 years; 54% female) were included. Real-life activity was measured over 4 days using wrist- and ankle-worn accelerometers. Unilateral arm and leg activity as well as arm/leg ratio were derived from vector magnitude counts per minute. Associations between accelerometer-based measures and clinical assessments of motor function, spasticity, activity capacity, and self-perceived activity performance were analyzed using Spearman's rank-order correlation. Results:Affected arm and leg real-life activity showed mostly moderate correlations with motor function and activity capacity assessments (ρ = 0.55-0.76), low correlations with spasticity assessments (ρ = -0.32 to -0.43) and high correlations with self-perceived manual and walking performance (ρ = 0.70-0.82). Arm activity ratio showed high correlations (ρ = 0.73-0.83) with motor function, activity capacity, and self-perceived performance. Real-life activity of the non-affected limbs demonstrated predominantly low correlations with clinical assessments. Conclusion:Accelerometer-based real-life activity measures of the affected arm and leg, along with activity ratios, provide clinically valid information regarding motor function and activity in people with disabling spasticity. Self-reported activity performance questionnaires can be valid tools for clinical practice when accelerometer-based measurements are not readily available.

Unsupervised HCL of an external dataset of breast cancer metastases (GSE14018) using the 358 "breast cancer liver metastasis-selective genes" derived from SAM analyses of metastases in the test dataset.

BackgroundPrestroke physical activity (PA) has been linked to improved outcomes after intracerebral haemorrhage (ICH), but its association with ICH volume is unknown. We aimed to investigate associations of prestroke PA with location-specific haematoma volume and the clinical outcome of ICH.MethodsAll patients with primary ICH, admitted to three hospitals between 2014 and 2019, were included. Patients performing light PA ≥4 hour/week the year before stroke were considered physically active. Haematoma volumes were assessed from admission brain imaging. Adjusted associations were estimated using multivariate linear and logistic regression models. Haematoma volume was explored as mediator to the relationship between prestroke PA and mild stroke severity (0–4 points on the National Institutes of Health Stroke Scale), a good 1-week functional status (0–3 points on the modified Rankin Scale) and 90-day survival. Average direct effects (ADE) and average causal mediation effects (ACME) were computed.ResultsOf 686 primary ICH cases, 349 were deep, 240 lobar and 97 infratentorial. Prestroke PA predicted smaller haematoma volumes in deep ICH (β=−0.36, SE=0.09, p<0.001) and lobar ICH (β=−0.23, SE=0.09, p=0.016). Prestroke PA was also associated with mild stroke severity (OR 2.53, 95% CI 1.59 to 4.01), a good 1-week functional status (OR 2.12, 95% CI 1.37 to 3.30) and 90-day survival (OR 3.48, 95% CI 2.06 to 5.91). Haematoma volume partly mediated the relationships between PA and stroke severity (ADE 0.08, p=0.004; ACME 0.10, p<0.001), 1-week functional status (ADE 0.07, p=0.03; ACME 0.10, p<0.001) and 90-day survival (ADE 0.14, p<0.001; ACME 0.05, p<0.001).ConclusionsLight PA ≥4 hour/week prior to ICH was associated with smaller haematoma volumes in deep and lobar locations. Physically active patients with ICH had a higher likelihood of mild stroke, a good 1-week functional status and 90-day survival, in part mediated by smaller haematoma volumes on admission.

A. Association between the 17-gene signature and IntClust subgroups. P-value is from anova test. B. Relapse free survival for the subset of patients in IntClust subgroups 3, 7 and 8, which are enriched for Luminal A tumors. 73% of tumors with high expression belonged to IntClust subgroup 3, while 41% of tumors with low expression were of subgroup 7 and 8. C. Associations between the 17 liver metastasis-selective genes and RFS and D. OS for all patients included in GOBO irrespective of ER status.

Objective: To examine the ability to perform basic and instrumental activities of daily life after very early supported discharge vs usual discharge and referral routine during the first year after mild stroke. Design: A secondary analysis of data from the Gothenburg Very Early Supported Discharge randomized controlled trial. Patients: A total of 104 patients (56% men; mean (standard deviation) age 75 (11) years) who had experienced a first stroke classified as mild. Methods: The primary outcome was the Activities of Daily Living Taxonomy score. Stroke Impact Scale (activities of daily living, and mobility) scores was a secondary measure. Patients were randomized to either very early supported discharge with 4 weeks of home rehabilitation provided by a multidisciplinary stroke team, or a control group discharged according to usual routine (referral to primary care when needed). Assessments were performed at discharge, 4 weeks post-discharge, and 3 and 12 months post-stroke. Results: Instrumental activities of the Activities of Daily Living Taxonomy scores (the lower the better) in the very early supported discharge and control groups were median 4 and 6 (p = 0.039) at 4 weeks post-discharge and 3 and 4.5 (p = 0.013 at 3 months post-stroke, respectively. Stroke Impact Scale (Mobility) median scores (the higher the better) in the very early supported discharge and control groups at 3 months were 97 and 86 (p = 0.040), respectively. There were no group differences in the 2 outcomes at 12 months post-stroke. Conclusion: Compared with usual discharge routine, team-based rehabilitation during the first month at home is beneficial for instrumental activity in the subacute phase, in patients with mild stroke. One year post-stroke both groups show equal results.

Gene ontology analysis showing significantly enriched GO-terms for biological process among the significantly altered genes in breast cancer liver metastases compared to metastases from other sites.

Abstract Purpose: The complete molecular basis of the organ-specificity of metastasis is elusive. This study aimed to provide an independent characterization of the transcriptional landscape of breast cancer metastases with the specific objective to identify liver metastasis–selective genes of prognostic importance following primary tumor diagnosis. Experimental Design: A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinicopathologic features were investigated. Fine-needle aspirates of metastases (n = 91) were subjected to whole-genome transcriptional profiling. Liver metastasis–selective genes were identified by significance analysis of microarray (SAM) analyses and independently validated in external datasets. Finally, the prognostic relevance of the liver metastasis–selective genes in primary breast cancer was tested. Results: Liver relapse was associated with estrogen receptor (ER) expression (P = 0.002), luminal B subtype (P = 0.01), and was prognostic for an inferior postrelapse survival (P = 0.01). The major variation in the transcriptional landscape of metastases was also associated with ER expression and molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by downregulation of extracellular matrix (i.e., stromal) genes. Importantly, we identified a 17-gene liver metastasis–selective signature, which was significantly and independently prognostic for shorter relapse-free (P < 0.001) and overall (P = 0.001) survival in ER-positive tumors. Remarkably, this signature remained independently prognostic for shorter relapse-free survival (P = 0.001) among luminal A tumors. Conclusions: Extracellular matrix (stromal) genes can be used to partition breast cancer by site of relapse and may be used to further refine prognostication in ER positive primary breast cancer. Clin Cancer Res; 22(1); 146–57. ©2015 AACR.

Background and Objectives Prestroke physical activity may protect the brain from severe consequences of stroke. However, previous studies on this subject included mainly ischemic stroke cases, and the association between prestroke physical activity and outcomes after intracerebral hemorrhage is uncertain. Therefore, we sought to examine the associations between prestroke physical activity, stroke severity, and all-cause mortality after intracerebral hemorrhage in comparison with ischemic stroke. Methods This was a longitudinal, register-based cohort study. All adult patients with intracerebral hemorrhage or ischemic stroke admitted to 3 stroke units in Gothenburg, Sweden, between November 1, 2014, and June 30, 2019, were screened for inclusion. Physical activity was defined as light physical activity >= 4 h/wk or moderate physical activity >= 2 h/wk the year before stroke. Stroke severity was assessed on admission using the NIH Stroke Scale. All-cause mortality rates were followed up to 7 years, from the time of incident stroke until death or censoring. Ordinal logit models and Cox proportional hazards models were used to estimate adjusted associations of prestroke physical activity. Results We included 763 patients with intracerebral hemorrhage and 4,425 with ischemic stroke. Prestroke physical activity was associated with less severe strokes by an adjusted odds ratio of 3.57 (99% CI 2.35-5.47) for intracerebral hemorrhages and 1.92 (99% CI 1.59-2.33) for ischemic strokes. During a median follow-up of 4.7 (interquartile range 3.5-5.9) years, 48.5% of patients with intracerebral hemorrhage died, compared with 37.5% with ischemic stroke. Prestroke physical activity was associated with decreased short-term mortality (0-30 days) by an adjusted hazard ratio of 0.30 (99% CI 0.17-0.54) after intracerebral hemorrhage and 0.22 (99% CI 0.13-0.37) after ischemic stroke. Prestroke physical activity was further associated with decreased long-term mortality (30 days-2 years) by an adjusted hazard ratio of 0.40 (99% CI 0.21-0.77) after intracerebral hemorrhage and 0.49 (99% CI 0.38-0.62) after ischemic stroke. Discussion Prestroke physical activity was associated with decreased stroke severity and all-cause mortality after intracerebral hemorrhage and ischemic stroke, independent of other risk factors. Based on current knowledge, health care professionals should promote physical activity as part of primary stroke prevention.

Paediatric brain tumours are rare, and establishing a precise diagnosis can be challenging. Analysis of DNA methylation profiles has been shown to be a reliable method to classify central nervous system (CNS) tumours with high accuracy. We aimed to prospectively analyse CNS tumours diagnosed in Sweden, to assess the clinical impact of adding DNA methylation‐based classification to standard paediatric brain tumour diagnostics in an unselected cohort.

Objective: This scoping review aims to identify how pre-stroke physical activity (PA) has been studied in relation to outcomes after stroke using the ICF framework. Methods: MEDLINE, CINAHL, Scopus, and grey literature databases were systematically searched from inception to March 15, 2021, with no language restrictions. Risk of bias was evaluated for all included studies. Identified outcome measures were linked to ICF components using linking rules, and the main findings were summarized. Results: Of 3664 records screened, 35 studies were included. The risk of bias was graded as moderate to critical for all studies. There were 60 unique outcome measures studied in relation to pre-stroke PA, covering the hyper acute to chronic phases of stroke recovery. Outcome measures linked to body functions were most common (n=19), followed by activities and participation (n=14), body structures (n=7), environmental factors (n=4) and personal factors (n=2). There were large differences in assessments of pre-stroke PA, and only one study analysed haemorrhagic cases separately. Conclusions: Pre-stroke PA has been studied in relation to all components in the ICF framework. However, this review highlights the high risk of bias, heterogeneity in pre-stroke PA assessments, and the lack of information regarding haemorrhagic strokes in the current literature. Lay Abstract We used the International Classification of Functioning, Disability and Health (ICF) to categorise the outcome measures of 35 studies. The ICF includes the following domains of health: body functions, body structures, activities, participation, and environmental factors. We identified 60 outcome measures, covering all domains of the ICF. Most common were measures related to body functions such as stroke symptoms, cognition or respiratory function, and activities or participation, such as functional recovery and walking ability. Few studies evaluated personal and environmental factors. Most studies collected information on physical activity before the stroke after the stroke had occurred, and all studies used self-reported information which is problematic from a scientific point of view and can lead to erroneous results. Future studies are needed to determine the true impact of physical activity on outcomes after stroke.

Objective: To determine to what extent accelerometer-based arm, leg and trunk activity is associated with sensorimotor impairments, walking capacity and other factors in subacute stroke. Design: Cross-sectional study. Patients: Twenty-six individuals with stroke (mean age 55.4 years, severe to mild motor impairment). Methods: Data on daytime activity were collected over a period of 4 days from accelerometers placed on the wrists, ankles and trunk. A forward stepwise linear regression was used to determine associations between free-living activity, clinical and demographic variables. Results: Arm motor impairment (Fugl-Meyer Assessment) and walking speed explained more than 60% of the variance in daytime activity of the more-affected arm, while walking speed alone explained 60% of the more-affected leg activity. Activity of the less-affected arm and leg was associated with arm motor impairment (R-2=0.40) and independence in walking (R-2 =0.59). Arm activity ratio was associated with arm impairment (R-2 =0.63) and leg activity ratio with leg impairment (R-2 =0.38) and walking speed (R-2 =0.27). Walking-related variables explained approximately 30% of the variance in trunk activity. Conclusion: Accelerometer-based free-living activity is dependent on motor impairment and walking capacity. The most relevant activity data were obtained from more-affected limbs. Motor impairment and walking speed can provide some information about real-life daytime activity levels.

Introduction: Movement related impairments and limitations in walking are common long-term after stroke. This multi-arm randomized controlled trial explored the impact of training with an electromechanically assisted gait training (EAGT) system, i.e., the Hybrid Assistive Limb® (HAL), when integrated with conventional rehabilitation focused on gait and mobility.Material and Methods: Participants, aged 18–70 years with lower extremity paresis but able to walk with manual support or supervision 1–10 years after stroke, were randomized to (A) HAL-training on a treadmill, combined with conventional rehabilitation interventions (HAL-group), or (B) conventional rehabilitation interventions only (Conventional group), 3 days/week for 6 weeks, or (C) no intervention (Control group). Participants in the Control group were interviewed weekly regarding their scheduled training. Primary outcome was endurance in walking quantified by the 6 Minute Walk Test (6MWT). A rater blinded to treatment allocation performed assessments pre- and post-intervention and at follow-ups at 6 and 12 months. Baseline assessment included the National Institute of Health Stroke Scale (NIHSS) and the Modified Ranking Scale (MRS). Secondary outcomes included the Fugl Meyer Assessment- Lower Extremity, 10 Meter Walk Test, Berg Balance Scale (BBS), Barthel Index (BI) and perceived mobility with the Stroke Impact Scale.Results: A total of 48 participants completed the intervention period. The HAL-group walked twice as far as the Conventional group during the intervention. Post-intervention, both groups exhibited improved 6 MWT results, while the Control group had declined. A significant improvement was only found in the Conventional group and when compared to the Control group (Tukey HSD p = 0.022), and not between the HAL group and Conventional group (Tukey HSD p = 0.258) or the HAL- group and the Control group (Tukey HSD p = 0.447). There was also a significant decline in the Conventional group from post-intervention to 6 months follow up (p = 0.043). The best fitting model to predict outcome included initial balance (BBS), followed by stroke severity (NIHSS), and dependence in activity and participation (BI and MRS).Conclusion: Intensive conventional gait training induced significant improvements long-term after stroke while integrating treadmill based EAGT had no additional value in this study sample. The results may support cost effective evidence-based interventions for gait training long-term after stroke and further development of EAGT.Trial registration: Published on clinicaltrials.gov (NCT02545088) August 24, 2015.

Background Radiation is an important therapeutic tool. However, radiotherapy has the potential to promote co-evolution of genetic and epigenetic changes that can drive tumour heterogeneity, formation of radioresistant cells and tumour relapse. There is a clinical need for a better understanding of DNA methylation alterations that may follow radiotherapy to be able to prevent the development of radiation-resistant cells. Methods We examined radiation-induced changes in DNA methylation profiles of paediatric glioma stem cells (GSCs) in vitro. Five GSC cultures were irradiated in vitro with repeated doses of 2 or 4 Gy. Radiation was given in 3 or 15 fractions. DNA methylation profiling using Illumina DNA methylation arrays was performed at 14 days post-radiation. The cellular characteristics were studied in parallel. Results Few fractions of radiation did not result in significant accumulation of DNA methylation alterations. However, extended dose fractionations changed DNA methylation profiles and induced thousands of differentially methylated positions, specifically in enhancer regions, sites involved in alternative splicing and in repetitive regions. Radiation induced dose-dependent morphological and proliferative alterations of the cells as a consequence of the radiation exposure. Conclusions DNA methylation alterations of sites with regulatory functions in proliferation and differentiation were identified, which may reflect cellular response to radiation stress through epigenetic reprogramming and differentiation cues.

Objective: A prospective, observational study to describe levels of physical activity in patients with stroke on day 2 and day 5 or 6 after admission to a comprehensive stroke unit in Sweden. Methods: The study was performed at the stroke unit at Sahlgrenska University Hospital during a period of 4 months between 2017 and 2018. Consecutive patients with stroke were observed for 1 min every 10 min while the multidisciplinary team was at work. The level of physical activity, location and the people present were noted at each time-point. Results: A total of 46 patients were observed on day 2, of whom 29 were observed a second time on day 5 or 6. Patients were in bed half of the time and engaged in upright activity for less than 10% of day 2. Patients spent 73% of day 2 in the bedroom and 56% of this day alone. Over time, there was a significant shift of 10% from "in bed" activity to "sitting" (p < 0.001). Conclusion: Patients are physically inactive, alone and in their rooms for a majority of the time during the first days at a comprehensive stroke unit. There is some increase in physical activity during the first week after admission.

Background Postural balance is an important rehabilitation outcome, and screening stroke patients for confidence in postural balance during rehabilitation and before hospital discharge is recommended. Early supported discharge could improve postural balance self-confidence. This study aimed to investigate associations between patient self-confidence in postural balance and observer-assessed postural balance and anxiety during the first year after stroke. Whether very early supported discharge (VESD) affects self-confidence in postural balance compared with standard discharge was also evaluated. Methods A longitudinal trial for with data extracted from a randomized controlled study of 140 adults with confirmed stroke was conducted. The experimental group received VESD. The control group was discharged according to the standard routine. Postural balance was assessed with Berg Balance Scale (BBS), Timed Up and Go (TUG) test, and Falls Efficacy Scale. Anxiety was assessed with the Hospital Anxiety and Depression Scale. Spearman’s rank correlation coefficient (rho) was used to test associations between independent variables. The Wilcoxon signed-rank test was used to examine differences over time. A single test, according to Eid, Gollwitzer, and Schmidt, was used to test temporal differences in correlation. Results The correlation between self-confidence in postural balance and observer-assessed postural balance was 0.62–0.78 in the first year after stroke. The correlation between self-confidence and anxiety was 0.22–0.41 in the first year after stroke. Correlations did not differ by group affiliation at any time point when the postural balance was assessed with BBS. The intervention group had a significantly higher correlation ( r = − 0.709) than the control group ( r = − 0.416) when postural balance was assessed with the TUG test 1 month after discharge. There were no significant differences in correlations between confidence in postural balance and anxiety between the two groups at any time point. Conclusions Patients with mild stroke can accurately assess their confidence in performing daily activities without falling. VESD does not substantially affect the correlation between self-confidence in postural balance and observer assessed postural balance and is safe to use as an alternative to standard discharge. Assessment of self-confidence can provide important information for rehabilitation planning and supporting the physical activity of patients after discharge. Trial registration Clinical Trials.gov: NCT01622205 . Registered 19 June 2012 (retrospectively registered).

Abstract Background and purpose Early supported discharge (ESD) has been shown to be efficient and safe as part of the stroke care pathway. The best results have been seen with a multidisciplinary team and after mild to moderate stroke. However, how very early supported discharge (VESD) works has not been studied. The aim of this study was to investigate whether VESD for stroke patients in need of ongoing individualized rehabilitation affects the level of anxiety and overall disability for the patient compared with ordinary discharge routine. Methods A randomized controlled trial was performed with intention to treat analyses comparing VESD and ordinary discharge from hospital. All patients admitted at the stroke care unit at Sahlgrenska University Hospital of Gothenburg between August 2011 and April 2016 were screened. Inclusion occurred on day 4 using a block randomization of 20 and with a blinded assessor. Assessments were made 5 days post-stroke and 3 and 12 months post-stroke. Patients in the VESD group underwent continued rehabilitation in their homes with a multidisciplinary team from the stroke care unit for a maximum of 1 month. The patients in the control group had support as usual after discharge when needed such as home care service and outpatient rehabilitation. The primary outcome was anxiety as assessed by the Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A). The secondary outcome was the patients’ degree of overall disability, measured by the modified Rankin Scale (mRS). Results No significant differences were found between the groups regarding anxiety at three or 12 months post-stroke (p = 0.811). The overall disability was significantly lower in the VESD group 3 months post-stroke (p = 0.004), compared to the control group. However, there was no significant difference between the groups 1 year post-stroke. Conclusions The VESD does not affects the level of anxiety compared to ordinary rehabilitation. The VESD leads to a faster improvement of overall disability compared to ordinary rehabilitation. We suggest considering coordinated VESD for patients with mild to moderate stroke in addition to ordinary rehabilitation as part of the service from a stroke unit. Trial registration Clinical Trials.gov: NCT01622205. Registered 19 June 2012 (retrospectively registered).

Background: Impaired postural balance is a common symptom after stroke and a common cause of falling. Most common daily tasks use arm and hand movements. Impairment in an upper extremity is a common stroke symptom, affecting 50-80% in the acute phase after stroke, and 40-50% in the sub-acute phase. The impact of leg function on postural balance has been investigated in several studies, but few have stressed the importance of arm function on postural balance. Objective: To explore whether there is any association between arm function and postural balance after stroke. Method: A cross sectional study where 121 adults (mean age: 70 ± 12.3 years, 72 men) from two different data sources, Gothenburg Very Early Supported Discharge (GOTVED), and a study by Carvalho et al. were merged. Time for assessments ranged from 1 to 13 years when the patients were in the chronic phase. The dependent variables were Berg Balance scale (BBS) and Time Up and Go (TUG) both dichotomized to "impaired postural balance" and "not impaired postural balance." As independent variables, the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) scale was used. The FMA-UE was presented with the total score. Results: The motor function in the arm affected after stroke onset correlated with postural balance both measured with the BBS (0.321, p < 0.001) and the TUG (-0.315, p = 0.001). Having impaired motor function in the arm was significantly associated with impaired postural balance assessed with the BBS with OR = 0.879 (CI 0.826-0.934, p < 0.001). Regression analysis with the TUG showed the same result, OR = 0.868 (CI 0.813-0.927, p < 0.001) for FM-UE. Conclusion: The motor function of the affected arm was significantly associated with impaired postural balance post stroke, as assessed by BBS or TUG. It could be of clinical importance to be aware of the fact that not only lower extremity impairment, but also arm function can have an impact on postural balance in a late stage after stroke. Trial Registration: VGFOUGSB-669501.

OBJECTIVE:To determine whether there are differences in arm, leg and trunk activity measured by acceleration between weekdays and weekends in people undergoing rehabilitation in the subacute stage after stroke.DESIGN:Cross-sectional study.PATIENTS:Twenty-eight individuals with stroke (mean age 55.4 years; severe to mild impairment) and 10 healthy controls.METHODS:A set of 5 3-axial accelerometers were used on the trunk, wrists and ankles during 2 48-h sessions at weekdays and over a weekend. Day-time acceleration raw data were expressed as the signal magnitude area. Asymmetry between the affected and less-affected limb was calculated as a ratio.RESULTS:Participants with stroke used their both arms and legs less at weekends than on weekdays (p< 0.05, effect size 0.32-0.57). Asymmetry between the affected and less-affected arm was greater at weekends (p < 0.05, effect size 0.32). All activity measures, apart from the less-affected arm on weekdays, were lower in stroke compared with controls (p < 0.05, effect size 0.4-0.8). No statistically significant differences were detected between weekday and weekend activity for the control group. One-third of participants perceived the trunk sensor as inconvenient to wear.CONCLUSION:Increased focus needs to be applied on activities carried out during weekends at rehabilitation wards.

Molecular classification of tumour clonality is currently not evaluated in multiple invasive breast carcinomas, despite evidence suggesting common clonal origins. There is no consensus about which type of data (e.g. copy number, mutation, histology) and especially which statistical method is most suitable to distinguish clonal recurrences from independent primary tumours.