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Abstract Background The role of single nucleotide polymorphisms (SNPs) associated with inflammatory bowel disease (IBD) is gaining interest. With the advent of novel therapies, personalized treatment in IBD is a future goal. We wondered whether IBD-associated SNPs are able to predict response to anti-TNFα treatment. Methods Data on treatment use and primary response, loss of response and side effects to anti-TNFα treatments were retrieved for 570 IBD patients. rs13361189 (IRGM), rs10210302 (ATG16L1), rs2066844, rs2066845, rs2066847 (NOD2), rs35873774 (XBP1), rs11175593 (LRRK2), rs11465804 (IL23R), rs2301436 (CCR6), rs744166 (STAT3) and rs4821544 (NCF4) SNP status were determined. Results No associations were found between genetic variants of the LRRK2, CCR6, IL23R and NCF4 genes and response to anti-TNFα. For NOD2 and XBP1 associations were found, however, these associations were not strong enough to survive multiple testing corrections. Strikingly, patients carrying the ATG16L1 T300A variant were more likely to be treated with adalimumab, even after correction for disease phenotype, disease behavior and age (p = 0.004, OR 2.8, CI 1.6–5.0). Conclusions Genetic polymorphisms in the known IBD-associated gene ATG16L1 correlate with requirement of treatment, suggesting a different IBD disease phenotype in these patients. Further investigation will need to elucidate the implications of these findings and identify the underlying disease characteristics.

BackgroundColonoscopic surveillance provides the best practical means for preventing colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients. Strong evidence for improved survival from surveillance programmes is sparse.MethodThe aim of this study was to compare tumour stage and survival of IBD patients with CRC who were a part of a surveillance programme with those who were not. A nationwide pathology database (PALGA (pathologisch anatomisch landelijk geautomatiseerd archief)) was consulted to identify IBD patients with CRC treated in all eight university hospitals in The Netherlands over a period of 15 years. Patients were assigned to the surveillance group when they had undergone one or more surveillance colonoscopies before a diagnosis of CRC. Patients who had not undergone surveillance served as controls. Tumour stage and survival were compared between the two groups.ResultsA total of 149 patients with IBD-associated CRC were identified. Twenty-three had had colonoscopic surveillance before CRC was discovered. The 5-year CRC-related survival rate of patients in the surveillance group was 100% compared with 74% in the non-surveillance group (P=0.042). In the surveillance group, only one patient died as a consequence of CRC compared with 29 patients in the control group (P=0.047). In addition, more early tumour stages were found in the surveillance group (P=0.004).ConclusionsThese results provide evidence for improved survival from colonoscopic surveillance in IBD patients by detecting CRC at a more favourable tumour stage.

This article explores the political and media discourse in The Netherlands around COVID-19 and migration. In so doing, it asks to what extent the dynamics of ‘governing COVID-19 through migration’ are visible in this discourse. By asking this question, the article builds upon the theoretical frameworks of ‘governing through crime’ and ‘governing through migration control’. Both theoretical frameworks place a strong emphasis on the role of discourse in framing certain social phenomena as a threat, concern or risk. By carrying out a discourse analysis on Dutch political and media debates around COVID-19 and migration in the period 1 January 2020–1 November 2021, the article illustrates that despite the linking of migration and crime not only being very visible but also seemingly normalized in this discourse, the links made between COVID-19 and migration were much more nuanced. Furthermore, although COVID-19 and migration were discussed together, the discourse does not show any evidence of governing COVID-19 through migration by using the pandemic to push for very restrictive migration laws targeting only ‘vagabonds’ while still allowing the mobility of ‘tourists’).

Up to 60% of patients experience recurrence after a first traumatic anterior shoulder dislocation (FTASD), which is often defined as having experienced either dislocation or subluxation. Thus surgical intervention after FTASD is worthy of consideration and is guided by the number of patients who need to receive surgical intervention to prevent 1 redislocation (i.e., number needed to treat), (subjective) health benefit, complication risk, and costs. Operative intervention through arthroscopic stabilization can be successful in reducing recurrence risk in FTASD, as has been shown in multiple randomized controlled trials. Nevertheless, there is a large "gray area" for the indication of arthroscopic stabilization, and it is therefore heavily debated which patients should receive operative treatment. Previous trials showed widely varying redislocation rates in both the intervention and control group, meta-analysis shows 2% to 19% after operative and 20% to 75% after nonoperative treatment, and redislocation rates may not correlate with patient-reported outcomes. The literature is quite heterogeneous, and a major confounder is time to follow-up. Furthermore, there is insufficient standardization of reporting of outcomes and no consensus on definition of risk factors. As a result, surgery is a reasonable intervention for FTASD patients, but in which patients it best prevents redislocation requires additional refinement. [ABSTRACT FROM AUTHOR]

Abstract Background Anti-carbamylated protein (anti-CarP) antibodies have recently been reported to occur in around 45% of rheumatoid arthritis (RA) patients and to have prognostic and diagnostic properties. At present, the breadth and molecular make-up of the anti-CarP antibody response is ill defined. To understand the anti-CarP antibody immune response and potential immune effector mechanisms it can recruit, we determined the anti-CarP antibody isotype and IgG-subclass usage in RA patients. Methods Anti-CarP antibody IgM, IgA, and IgG or IgG subclasses were detected by enzyme-linked immunosorbent assay (ELISA) in sera from 373 unselected RA patients and 196 healthy controls. An additional 114 anti-citrullinated protein antibody (ACPA) and anti-CarP IgG double-positive patients were selected to study the concomitant presence of both antibody systems. Results Anti-CarP IgG was present in around 45% of the patients and comprised all anti-CarP IgG subclasses. The presence of anti-CarP IgG1 particularly associates with radiological damage. Anti-CarP IgM was detected in 16% of RA patients, even in anti-CarP IgG-positive individuals, and is indicative of an actively ongoing immune response. Around 45% of the patients were positive for IgA which included ACPA-positive cases but also 24% of the ACPA-negative cases. In ACPA and anti-CarP double-positive patients, the distribution and number of isotypes and IgG subclasses was similar for both autoantibodies at the group level, but substantial variation was observed within individual patient samples. Conclusions In RA, the anti-CarP antibody response uses a broad spectrum of isotypes and seems to be an actively ongoing immune reaction. Furthermore, the anti-CarP and ACPA autoantibody responses seems to be differentially regulated.

Lauran Vogelaar, 1,* Colin de Haar,2,* Bas RJ Aerts,1 Maikel P Peppelenbosch,1 Reinier Timman,3 Bettina E Hanssen,1 C Janneke van der Woude1 1Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, 2Applied Tumor Immunology, Laboratory of Translational Immunology, UMC Utrecht, Utrecht, 3Department of Psychiatry, Section of Medical Psychology and Psychotherapy, Erasmus MC, Rotterdam, the Netherlands *These authors contributed equally to this work Background: Although it is well recognized that fatigue is an important problem in many of the quiescent inflammatory bowel disease (IBD) patients, it is unknown whether the immune status is different in fatigued versus non-fatigued patients. In this study, we contrasted various characteristics of the immune system in fatigued against non-fatigued patients with IBD in clinical remission.Patients and methods: Patients with IBD in clinical remission were phenotyped according to the Montreal classification, and the checklist individual strength-fatigue (CIS-fatigue) was used to assess fatigue (CIS-fatigue ≥ 35). Flow cytometry on peripheral blood samples was used to investigate differences in leukocyte subsets. The expression of various cytokines was determined in stimulated whole blood and serum samples using enzyme-linked immunosorbent assay. Differences between fatigued and non-fatigued patients with IBD were assessed.Results: In total, 55 patients were included in the fatigue group (FG) and 29 patients in the non-fatigue group (NFG). No differences in demographic and clinical characteristics were observed between the groups. Flow cytometry data showed a significantly lower percentage of monocytes (p = 0.011) and a higher percentage of memory T-cells (p = 0.005) and neutrophils (p = 0.033) in the FG compared with the NFG. Whole blood stimulation showed increased TNF-α (p = 0.022) and IFN-γ (p = 0.047) in the FG. The median serum level was significantly higher for IL-12 (p

Abstract Background The Lokomat is a robotic exoskeleton that can be used to train gait function in hemiparetic stroke. To purposefully employ the Lokomat for training, it is important to understand (1) how Lokomat guided walking affects muscle activity following stroke and how these effects differ between patients and healthy walkers, (2) how abnormalities in the muscle activity of patients are modulated through Lokomat guided gait, and (3) how temporal step characteristics of patients were modulated during Lokomat guided walking. Methods Ten hemiparetic stroke patients (>3 months post-stroke) and ten healthy age-matched controls walked on the treadmill and in the Lokomat (guidance force 50%, no bodyweight support) at matched speeds (0.56 m/s). Electromyography was used to record the activity of Gluteus Medius, Biceps Femoris, Vastus Lateralis, Medial Gastrocnemius and Tibialis Anterior, bilaterally in patients and of the dominant leg in healthy walkers. Pressure sensors placed in the footwear were used to determine relative durations of the first double support and the single support phases. Results Overall, Lokomat guided walking was associated with a general lowering of muscle activity compared to treadmill walking, in patients as well as healthy walkers. The nature of these effects differed between groups for specific muscles, in that reductions in patients were larger if muscles were overly active during treadmill walking (unaffected Biceps Femoris and Gluteus Medius, affected Biceps Femoris and Vastus Lateralis), and smaller if activity was already abnormally low (affected Medial Gastrocnemius). Also, Lokomat guided walking was associated with a decrease in asymmetry in the relative duration of the single support phase. Conclusions In stroke patients, Lokomat guided walking results in a general reduction of muscle activity, that affects epochs of overactivity and epochs of reduced activity in a similar fashion. These findings should be taken into account when considering the clinical potential of the Lokomat training environment in stroke, and may inform further developments in the design of robotic gait trainers.

The purpose of the current study was to assess the inter-trial reliability and construct validity (talented juniors vs. international adult players) of four wheelchair tennis field tests using inertial measurement units (IMUs). Twenty-one elite wheelchair tennis players completed four tests, which evaluate the sprinting and manoeuvrability abilities in wheelchair tennis. During all tests 3 IMUs were attached to both wheels and the frame of the athlete's wheelchair. The IMUs enabled analysis of individual test dynamic characteristics, i.e. the linear/rotational velocity and acceleration data, as well as detected pushes. All tests showed high ICCs (0.95-0.99) for the inter-trial reliability for the IMU-based end times and also the construct validity was good, i.e. talented juniors could be discriminated from international adults. Also, velocities and accelerations during the tests could be consistently visualized, meaning that differences in test performance among participants could be designated. Within the experimental context, the field tests could be regarded as reliable and valid. With the use of IMUs it is possible to verify more detailed performance characteristics, visualize the test execution, as well as differentiate between a talented junior and international adult group and within individuals over time.

BACKGROUND:The Pregnane X Receptor (PXR) is a principal signal transducer in mucosal responses to xenobiotic stress. It is well-recognized that inflammatory bowel disease is accompanied by xenobiotic stress, but the importance of the PXR in limiting inflammatory responses in inflammatory bowel disease remains obscure at best. METHODS:We stimulate a total of 106 colonic biopsies from 19 Crohn's disease patients with active disease, 36 colonic biopsies from 8 control patients, colonic organoids and various cell culture models (either proficient or genetically deficient with respect to PXR) in vitro with the PXR ligand rifampicin or vehicle. Effects on NF-κB activity are assessed by measuring interleukin-8 (IL-8) and interleukin-1ß (IL-1ß) mRNA levels by qPCR and in cell culture models by NF-κB reporter-driven luciferase activity and Western blot for signal transduction elements. RESULTS:We observe a strict inverse correlation between colonic epithelial PXR levels and NF-κB target gene expression in colonic biopsies from Crohn's disease patients. PXR, activated by rifampicin, is rate-limiting for mucosal NF-κB activation in IBD. The correlation between colonic epithelial PXR levels and NF-κB target gene expression was also observed in intestinal organoids system. Furthermore, in preclinical in vitro models of intestinal inflammation, including intestinal organoids, genetic inactivation of PXR unleashes NF-κB-dependent signal transduction whereas conversely NF-κB signaling reduces levels of PXR expression. CONCLUSIONS:Our data indicate that the PXR is a major and clinically relevant antagonist of NF-κB activity in the intestinal epithelial compartment during inflammatory bowel disease.

ObjectiveThe objective of the current study was to investigate the effect of four different crank fore-aft positions on elbow flexion and shoulder protraction, the consequent propulsion kinetics and the physiological responses during handcycling.MethodsTwelve able-bodied male participants volunteered in this study. Crank fore-aft positions were standardised at 94%, 97%, 100% and 103% of the participants' arm length. Two submaximal 3 min trials were performed at a fixed cadence (70 rpm), in a recumbent handcyle attached to an ergometer at two fixed power outputs (30W and 60W). Elbow flexion, shoulder protraction, propulsion kinetics and physiological responses of the participants were continuously measured.ResultsAs crank fore-aft distance increased, a decrease in elbow flexion (42±4, 37±3, 33±3, 29±3°) and an increase shoulder protraction was observed (29±5, 31±5, 34±5, 36±5°). The percentage of work done in the pull phase increased as well (62±7, 65±7, 67±6, 69±8%, at 60W), which was in line with an increased peak torque during the pull phase (8.8±1.6, 9.0±1.4, 9.4±1.5, 9.7±1.4Nm, at 60W) and reduced peak torque during the push phase (6.0±0.9, 5.6±0.9,5.6±0.9, 5.4±1.0Nm, in 60W condition). Despite these changes in work distribution, there were no significant changes in gross mechanical efficiency (15.7±0.8, 16.2±1.1, 15.8±0.9, 15.6±1.0%, at 60W). The same patterns were observed in the 30W condition.ConclusionsFrom a biomechanical perspective the crank position closest to the trunk (94%) seems to be advantageous, because it evens the load over the push and pull phase, which reduces speed fluctuations, without causing an increase in whole body energy expenditure and hence a decrease of gross mechanical efficiency. These findings may help handcyclists to optimize their recumbent handcycle configuration.

Influenza vaccination can be less effective in patients treated with immunosuppressive therapy. However, little is known about the effects of ustekinumab; an anti-IL-12/23 agent used to treat Crohn’s disease (CD), on vaccination response. In this prospective study, we assessed immune responses to seasonal influenza vaccination in CD patients treated with ustekinumab compared to CD patients treated with anti-TNFα therapy (adalimumab) and healthy controls. Humoral responses were assessed with hemagglutinin inhibition (HI) assays. Influenza-specific total CD3+, CD3+CD4+, and CD3+CD8+ T-cell responses were measured with flow cytometry. Fifteen patients treated with ustekinumab; 12 with adalimumab and 20 healthy controls were vaccinated for seasonal influenza in September 2018. Seroprotection rates against all vaccine strains in the ustekinumab group were high and comparable to healthy controls. Seroconversion rates were comparable, and for A/H3N2 highest in the ustekinumab group. HI titers were significantly higher in the ustekinumab group and healthy controls than in the adalimumab group for the B/Victoria strain. Post-vaccination T-cell responses in the ustekinumab group were similar to healthy controls. One-month post-vaccination proliferation of CD3+CD8+ T-cells was highest in the ustekinumab group. In conclusion, ustekinumab does not impair immune responses to inactivated influenza vaccination. Therefore, CD patients treated with ustekinumab can be effectively vaccinated for seasonal influenza.

Fatigue is common in people with multiple sclerosis (MS). Activity pacing is a behavioral way to cope with fatigue and limited energy resources. However, little is known about how people with MS naturally pace activities to manage their fatigue and optimize daily activities. This study explored how activity pacing relates to fatigue and physical activity in people with MS. Participants were 80 individuals (60 females, 20 males) with a diagnosis of MS. The participants filled in questionnaires on their activity pacing, fatigue, physical activity, and health-related quality of life, 3–6 weeks before discharge from rehabilitation. The relationships between the variables were examined using hierarchical regression. After controlling for demographics, health-related quality of life, and perceived risk of overactivity, no associations were found between activity pacing and fatigue (β = 0.20; t = 1.43, p = 0.16) or between activity pacing and physical activity (β = −0.24; t = −1.61, p = 0.12). The lack of significant associations between activity pacing and fatigue or physical activity suggests that without interventions, there appears to be no clear strategy amongst people with MS to manage fatigue and improve physical activity. People with MS may benefit from interventions to manage fatigue and optimize engagement in physical activity.

This article evaluates the factors involved in the acceptance of Blended Learning (BL) with executives based on the Extended Unified Theory of Acceptance and Use of Technology (UTAUT2) model in executive education. The empirical analysis uses data from 307 responses to an online questionnaire by senior and middle-ranking managers. The confirmatory factor analysis and structural equation modeling demonstrated the applicability of the UTAUT2 model in BL in executive education. The results showed that hedonic motivation, performance expectancy, and effort expectancy predict the intention to adopt BL. Results also prove no significant effect on social influence and habits. The relevance of this article is to contribute to the understanding of the factors that influence the intention to adopt BL in a group not typically considered in higher education research.

Ambient temperature affects plant growth and even minor changes can substantially impact crop yields. The underlying mechanisms of temperature perception and response are just beginning to emerge. Chromatin remodeling, via the eviction of the histone variant H2A.Z containing nucleosomes, is a critical component of thermal response in plants. However, the role of histone modifications remains unknown. Here, through a forward genetic screen, we identify POWERDRESS (PWR), a SANT-domain containing protein known to interact with HISTONE DEACETYLASE 9 (HDA9), as a novel factor required for thermomorphogenesis in Arabidopsis thaliana. We show that mutations in PWR impede thermomorphogenesis, exemplified by attenuated warm temperature-induced hypocotyl/petiole elongation and early flowering. We show that inhibitors of histone deacetylases diminish temperature-induced hypocotyl elongation, which demonstrates a requirement for histone deacetylation in thermomorphogenesis. We also show that elevated temperature is associated with deacetylation of H3K9 at the +1 nucleosomes of PHYTOCHROME INTERACTING FACTOR4 (PIF4) and YUCCA8 (YUC8), and that PWR is required for this response. There is global misregulation of genes in pwr mutants at elevated temperatures. Meta-analysis revealed that genes that are misregulated in pwr mutants display a significant overlap with genes that are H2A.Z-enriched in their gene bodies, and with genes that are differentially expressed in mutants of the components of the SWR1 complex that deposits H2A.Z. Our findings thus uncover a role for PWR in facilitating thermomorphogenesis and suggest a potential link between histone deacetylation and H2A.Z nucleosome dynamics in plants.

BACKGROUND:Physical fitness of patients with a lower limb amputation predicts their walking ability and may be improved by physical exercise and training. A maximal exercise test is recommended prior to training in order to determine cardiovascular risks and design exercise programs. A potentially suitable ergometer for maximal exercise testing in patients with a lower limb amputation is the combined arm-leg (Cruiser) ergometer. The aim of this study was to determine feasibility, safety, and reliability of (sub)maximal exercise testing on the Cruiser ergometer in subjects with a lower limb amputation. METHODS AND FINDINGS:Subjects with a lower limb amputation performed 1 submaximal exercise test and 3 maximal exercise tests on the Cruiser ergometer. Feasibility was determined by examining whether key variables such as power output, heart rate and oxygen uptake were correctly and reliably measured, by determining whether a test was a maximal aerobic performance, by studying reasons for non-completion, and by measuring gross efficiency. Safety was analyzed by recording complications, electrocardiogram results, and blood pressure. Reliability was tested by comparing the results of the second and third maximal exercise test. Seventeen subjects (14 men and 3 women) out of 21 preselected subjects completed the study. In general, the maximal Cruiser exercise test was feasible. Almost 75% of the subjects reached a maximal aerobic performance. The test was also safe because no complications occurred, although electrocardiogram and blood pressure could only be reliably recorded in most subjects just before and after the test. Reliability was good: Intraclass correlation was 0.84 for peak oxygen uptake. CONCLUSIONS:The Cruiser ergometer is a feasible, safe, and reliable ergometer for measuring physical fitness of subjects with a lower limb amputation.

In this study we investigate a CT radiomics approach to predict response to chemotherapy of individual liver metastases in patients with esophagogastric cancer (EGC). In eighteen patients with metastatic EGC treated with chemotherapy, all liver metastases were manually delineated in 3D on the pre-treatment and evaluation CT. From the pre-treatment CT scans 370 radiomics features were extracted per lesion. Random forest (RF) models were generated to discriminate partial responding (PR, >65% volume decrease, including 100% volume decrease), and complete remission (CR, only 100% volume decrease) lesions from other lesions. RF-models were build using a leave one out strategy where all lesions of a single patient were removed from the dataset and used as validation set for a model trained on the lesions of the remaining patients. This process was repeated for all patients, resulting in 18 trained models and one validation set for both the PR and CR datasets. Model performance was evaluated by receiver operating characteristics with corresponding area under the curve (AUC). In total 196 liver metastases were delineated on the pre-treatment CT, of which 99 (51%) lesions showed a decrease in size of more than 65% (PR). From the PR set a total of 47 (47% of RL, 24% of initial) lesions were no longer detected in CT scan 2 (CR). The RF-model for PR lesions showed an average training AUC of 0.79 (range: 0.74-0.83) and 0.65 (95% ci: 0.57-0.73) for the combined validation set. The RF-model for CR lesions had an average training AUC of 0.87 (range: 0.83-0.90) and 0.79 (95% ci 0.72-0.87) for the validation set. Our findings show that individual response of liver metastases varies greatly within and between patients. A CT radiomics approach shows potential in discriminating responding from non-responding liver metastases based on the pre-treatment CT scan, although further validation in an independent patient cohort is needed to validate these findings.

BACKGROUND:Up to 80% of wheelchair users are affected by shoulder pain. The Clinical Practice Guidelines for preservation of upper limb function following spinal cord injury suggest that using a proper wheelchair propulsion technique could minimize the shoulder injury risk. Yet, the exact relationship between the wheelchair propulsion technique and shoulder load is not well understood. OBJECTIVE:This study aimed to examine the changes in shoulder loading accompanying the typical changes in propulsion technique following 80 min of low-intensity wheelchair practice distributed over 3 weeks. METHODS:Seven able-bodied participants performed the pre- and the post-test and 56 min of visual feedback-based low-intensity wheelchair propulsion practice. Kinematics and kinetics of propulsion technique were recorded during the pre- and the post-test. A musculoskeletal model was used to calculate muscle force and glenohumeral reaction force. RESULTS:Participants decreased push frequency (51→36 pushes/min, p = 0.04) and increased contact angle (68→94°, p = 0.02) between the pre- and the post-test. The excursion of the upper arm increased, approaching significance (297→342 mm, p = 0.06). Range of motion of the hand, trunk and shoulder remained unchanged. The mean glenohumeral reaction force per cycle decreased by 13%, approaching significance (268→232 N, p = 0.06). CONCLUSIONS:Despite homogenous changes in propulsion technique, the kinematic solution to the task varied among the participants. Participants exhibited two glenohumeral reaction force distribution patterns: 1) Two individuals developed high force at the onset of the push, leading to increased peak and mean glenohumeral forces 2) Five individuals distributed the force more evenly over the cycle, lowering both peak and mean glenohumeral forces.

BACKGROUND:To accommodate training for unilaterally affected patients (e.g. stroke), the Lokomat (a popular robotic exoskeleton-based gait trainer) provides the possibility to set the amount of movement guidance for each leg independently. Given the interlimb couplings, such asymmetrical settings may result in complex effects, in which ipsilateral activity co-depends on the amount of guidance offered to the contralateral leg. To test this idea, the effect of asymmetrical guidance on muscle activity was explored. METHODS:15 healthy participants walked in the Lokomat at two speeds (1 and 2 km/h) and guidance levels (30% and 100%), during symmetrical (both legs receiving 30% or 100% guidance) and asymmetrical conditions (one leg receiving 30% and the other 100% guidance) resulting in eight unique conditions. Activity of the right leg was recorded from Erector Spinae, Gluteus Medius, Biceps Femoris, Semitendinosus, Vastus Medialis, Rectus Femoris, Medial Gastrocnemius and Tibialis Anterior. Statistical Parametric Mapping was used to assess whether ipsilateral muscle activity depended on guidance settings for the contralateral leg. RESULTS:Muscle output amplitude not only depended on ipsilateral guidance settings, but also on the amount of guidance provided to the contralateral leg. More specifically, when the contralateral leg received less guidance, ipsilateral activity of Gluteus Medius and Medial Gastrocnemius increased during stance. Conversely, when the contralateral leg received more guidance, ipsilateral muscle activity for these muscles decreased. These effects were specifically observed at 1 km/h, but not at 2 km/h. CONCLUSIONS:This is the first study of asymmetrical guidance on muscle activity in the Lokomat, which shows that ipsilateral activity co-depends on the amount of contralateral guidance. In therapy, these properties may be exploited e.g. to promote active contributions by the more affected leg. Therefore, the present results urge further research on the use of asymmetrical guidance in patient groups targeted by Lokomat training.

To assess the therapeutic validity and effectiveness of physiotherapeutic exercise interventions following total hip arthroplasty (THA) for osteoarthritis.The databases Embase, MEDLINE, Cochrane Library, CINAHL and AMED were searched from inception up to February 2017.Articles reporting results of randomized controlled trials in which physiotherapeutic exercise was compared with usual care or with a different type of physiotherapeutic exercise were included, with the applied interventions starting within six months after THA. Only articles written in English, German or Dutch were included.Therapeutic validity (using the CONTENT scale) and risk of bias (using both the PEDro scale and the Cochrane Collaboration's tool) were assessed by two researchers independently. Characteristics of the physiotherapeutic exercise interventions and results about joint and muscle function, functional performance and self-reported outcomes were extracted.Of the 1124 unique records retrieved, twenty articles were included. Only one article was considered to be of high therapeutic validity. Description and adequacy of patient selection were the least reported items. The majority of the articles was considered as having potentially high risk of bias, according to both assessment tools. The level of therapeutic validity did not correspond with the risk of bias scores. Because of the wide variety in characteristics of the physiotherapeutic exercise and control interventions, follow-up length and outcome measures, limited evidence was found on the effectiveness of physiotherapeutic exercise following THA.The insufficient therapeutic validity and potentially high risk of bias in studies involving physiotherapeutic exercise interventions limit the ability to assess the effectiveness of these interventions following THA. Researchers are advised to take both quality scores into account when developing and reporting studies involving physiotherapeutic exercise. Uniformity in intervention characteristics and outcome measures is necessary to enhance the comparability of clinical outcomes between trials.

Hypoactive lifestyle contributes to the development of secondary complications and lower quality of life in wheelchair users. There is a need for objective and user-friendly physical activity monitors for wheelchair-dependent individuals in order to increase physical activity through self-monitoring, goal setting, and feedback provision.To determine the validity of Activ8 Activity Monitors to 1) distinguish two classes of activities: independent wheelchair propulsion from other non-propulsive wheelchair-related activities 2) distinguish five wheelchair-related classes of activities differing by the movement intensity level: sitting in a wheelchair (hands may be moving but wheelchair remains stationary), maneuvering, and normal, high speed or assisted wheelchair propulsion.Sixteen able-bodied individuals performed sixteen various standardized 60s-activities of daily living. Each participant was equipped with a set of two Activ8 Professional Activity Monitors, one at the right forearm and one at the right wheel. Task classification by the Active8 Monitors was validated using video recordings. For the overall agreement, sensitivity and positive predictive value, outcomes above 90% are considered excellent, between 70 and 90% good, and below 70% unsatisfactory.Division in two classes resulted in overall agreement of 82.1%, sensitivity of 77.7% and positive predictive value of 78.2%. 84.5% of total duration of all tasks was classified identically by Activ8 and based on the video material. Division in five classes resulted in overall agreement of 56.6%, sensitivity of 52.8% and positive predictive value of 51.9%. 59.8% of total duration of all tasks was classified identically by Activ8 and based on the video material.Activ8 system proved to be suitable for distinguishing between active wheelchair propulsion and other non-propulsive wheelchair-related activities. The ability of the current system and algorithms to distinguish five various wheelchair-related activities is unsatisfactory.

This article focuses on how the Schengen Governance Package, and in particular the revised legal framework on the temporary reinstatement of internal border checks, should be valued within the broader process of crimmigration. First we elaborate upon both the recent incidents that underline the criminalization of migration in Europe and the recent developments in the Schengen legal framework on internal border control. Subsequently, based on an analysis of official notification letters issued by the respective Member States, we analyse the development of how often, and on which grounds, they temporarily closed their internal borders in the period of January 2000 - March 2014. In doing so, we pay attention not only to the question whether Member States have been using (the fear of) (cr)immigration as a reason to invoke the exception clause, but also to the transparency of the procedures that were followed. Following an assessment of the Schengen Governance Package in light of this analysis, we address certain other forms of border control developing within the Schengen zone. In conclusion, we argue that the way in which the European Commission and the Council responded to immigration-related anxieties is understandable but might have contrary effects in the long run.

With the introduction of an add-on handcycle, a crank system that can be placed in front of a wheelchair, handcycling was made widely available for daily life. With it, people go into town more easily, e.g. to do groceries; meet up with friends, etc. They have more independency and can be socially active. Our aim is to explore some settings of the handcycle, so that it can be optimally used as a transportation device. Therefore, the effects of cadence and added resistance on gross mechanical efficiency and force application during sub-maximal synchronous handcycling were investigated. We hypothesized that a cadence of 52 rpm with a higher resistance (35 W) would lead to a higher gross mechanical efficiency and a more tangential force application than a higher cadence of 70 rpm and no extra resistance (15 W).Twelve able-bodied men rode in an instrumented add-on handcycle on a motorized level treadmill at 1.94 m/s. They performed three sessions of three four-minute blocks of steady state exercise. Gear (70, 60 and 52 rpm) was changed in-between the blocks and resistance (rolling resistance +0 W, +10 W, +20 W) was changed across sessions, both in a counterbalanced order. 3D force production, oxygen uptake and heart rate were measured continuously. Gross mechanical efficiency (ME) and fraction of effective force (FEF) were calculated as main outcomes. The effects of cadence and resistance were analyzed using a repeated measures ANOVA (P

In recent years the popularity of disabled sports and competition among disabled athletes has grown considerably. With this rise in exposure of, and participation in wheelchair sports comes an increase in related stressors, including musculoskeletal load. External mechanical loading may increase the risk of shoulder complaints. The objective of this literature review was to 1) identify and describe the prevalence and/or incidence of shoulder complaints in wheelchair athletes in the literature, to 2) examine the factors and underlying mechanisms that could be potentially involved, and 3) provide some insights into the development of preventative measures.A literature search was conducted using PubMed, Scopus and Embase databases, to identify relevant published articles. All articles in the English language that contained any type of shoulder complaint in relation with a wheelchair sports player, at any level of status (recreational to elite), of any sport, were included. Articles were excluded if they did not include any statistical analysis. Articles that included studies with wheelchair athletes in combination with athletes of other disability sports were excluded in order to be able to differentiate between the two. Narrative, exploratory and case studies were also excluded. Two reviewers independently assessed articles for inclusion. Thirteen articles matched the selection criteria. These were judged on their quality by use of an adapted version of the Webster checklist.Of the included studies the overall quality was low. A relatively high prevalence of complaints was found, ranging from 16% to 76%. Pain was found to be a common complaint in wheelchair athletes. Based on the current literature the cause of shoulder problems is difficult to identify and is likely multifactorial, nevertheless characteristics of the user (i.e. increased years of disability, age and BMI) were shown to increase risk. Preventative measures were indistinct. There may be a role for balanced strength training regimens to decrease risk.Shoulder complaints in wheelchair athletes are a common problem that must be addressed further. Future studies on shoulder overuse injuries of wheelchair athletes should be directed towards biomechanical modeling to develop knowledge of load and its effects.

SH2 domain containing inositol-5-phosphatase (SHIP1) is an important modulator of innate and adaptive immunity. In mice, loss of SHIP1 provokes severe ileitis resembling Crohn's disease (CD), as a result of deregulated immune responses, altered cytokine production and intestinal fibrosis. Recently, SHIP1 activity was shown to be correlated to the presence of a CD-associated single nucleotide polymorphism in ATG16L1. Here, we studied SHIP1 activity and expression in an adult cohort of CD patients.SHIP1 activity, protein and mRNA expression in peripheral blood mononuclear cells from CD patients in clinical remission were determined by Malachite green assay, Western blotting and qRT-PCR respectively. Genomic DNA was genotyped for ATG16L1 rs2241880.SHIP1 protein levels are profoundly diminished in a subset of patients; however, SHIP1 activity and expression are not correlated to ATG16L1 SNP status in this adult cohort.Aberrant SHIP1 activity can contribute to disease in a subset of adult CD patients, and warrants further investigation.