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ObjectivesTo evaluate the effectiveness of a trainer-supervised judo-specific injury prevention warm-up programme on overall injury prevalence.MethodsWe conducted a two-arm, cluster randomised controlled trial; the Injury Prevention and Performance Optimization Netherlands (IPPON) study. Judo athletes aged≥12 years were randomised by judo school to IPPON intervention or control group who performed their usual warm-up. Primary outcome was overall injury prevalence (%) over the follow-up period (16–26 weeks) measured fortnightly with the Oslo Sports and Trauma Research Centre Questionnaire. A modified intention-to-treat analysis was performed due to COVID-19, with estimates for the primary outcome obtained using generalised linear mixed models. Secondary outcomes included: prevalence of severe injuries, overall incidence, time-loss injuries, exposure, adherence and experiences of trainers and athletes.Results269 judo athletes (IPPON: 117, Control: 152) were included. Mean injury prevalence over 16–26 weeks was 23% (95% CI 20% to 26%) in the IPPON and 28% (95% CI 25% to 30%) in the control group. We observed no significant difference of all reported injuries (OR 0.72 in favour of the IPPON group; 95% CI 0.37 to 1.39). Secondary outcomes also demonstrated no significant differences between groups. Specifically, no significant difference of severe injuries was reported (OR 0.80 in favour of the IPPON group; 95% CI 0.36 to 1.78). All trainers and 70% of athletes perceived the IPPON intervention as successful.ConclusionThe IPPON intervention did not significantly reduce the overall and severe injury prevalence. Despite this, we suggest the IPPON intervention be considered as an useful alternative to regular judo warm-up, given the high adherence and the positive clinical experiences of trainers and athletes.Trial registration numberNTR7698.

AbstractIndustrial land expansion has become a matter of increasing concern to policy-makers, especially in developing and emerging manufacturing countries. Price mechanisms are regarded as an important way to control the expansion of industrial land. For industrial land, the effectiveness of a price mechanism in controlling land expansion relies substantially on the substitutability of land in production, which remains unclear in the literature. This paper provides empirical evidence on the substitutability of industrial land by examining the impact of increases in land prices on the elasticity of substitution between land input and other production factors based on China’s city-level industrial production in 2007–2015. We find that land price increases significantly induce the industrial sector to reduce land demand by substituting capital for land. However, our estimated elasticity of substitution of capital for land in production is only 0.03, which indicates that industrial land is substitutable but the degree of substitutability is very low in production. The findings of our study suggest that the benefits of relying on price mechanisms to curb industrial land expansion may be very limited; hence, traditional planning instruments should also be suitably designed to jointly curb industrial land expansion.

ABSTRACTThis paper focuses on the influence of land and property privatization processes on urban development in Ho Chi Minh City (HCMC), Vietnam. Many scholars have recognized that the privatization policy regarding property and land use rights may create a fragmentation of private land ownership, which eventually can lead to what has been called the tragedy of the anticommons. This paper observes how this phenomenon has also threatened urban development in HCMC after the introduction of the Doi Moipolicy. Two case studies show two different types of development processes in HCMC, namely a small self-development project and a large-scale commercial project. Both case studies reveal how (potential) tragedies of the anticommons can be solved in different ways.

•We investigate the correlations between the urban form and Active School Travel.•Urban form around homes and schools can influence walking differently than cycling.•Interventions encouraging AST should be location-, mode- and target group-specific.•‘Soft’ strategies could focus on students and parents living in immediate school surroundings.•Minimising parental concerns could be relevant for students living beyond walkable but within reasonable cycling distances to school.

Background: Paralympic swimmers with vision impairment (VI) currently compete in one of the three classes depending on their visual acuity (VA) and/or visual field. However, there is no evidence to suggest that a three-class system is the most legitimate approach for classification in swimming, or that the tests of VA and visual field are the most suitable. An evidence-based approach is required to establish the relationship between visual function and performance in the sport. Therefore, the aim of this study was to establish the relationship between visual function and performance in VI Para swimming. The swimming performance of 45 elite VI swimmers was evaluated during international competitions by measuring the total race time, start time, clean swim velocity, ability to swim in a straight line, turn time, and finish time. Visual function was measured using a test battery that included VA, contrast sensitivity, light sensitivity, depth perception, visual search, and motion perception. Results: Results revealed that VA was the best predictor of total race time (r= 0.40, p< 0.01), though the relationship was not linear. Decision tree analysis suggested that only two classes were necessary for legitimate competition in VI swimming, with a single cut-off between 2.6 and 3.5 logMAR. No further significant association remained between visual function and performance in either of the two resulting classes (all |rs|< 0.11 and ps > 0.54). Conclusions: Results suggest that legitimate competition in VI swimming requires one class for partially sighted and another for functionally blind athletes.

Treatment of patients with rheumatoid arthritis (RA) is rarely personalized, since predictors of disease course are lacking. The severity of RA can be measured objectively by radiographic progression. The most reliable way to measure radiographic progression is in a longitudinal cohort with serial time points, scoring on a quantitative scale, with a validated scoring method and trained readers. Current models used to predict radiographic progression are based on C-reactive protein and anti-citrullinated protein antibodies. Other biomarkers could increase the prognostic ability of these models. In this review, we evaluated the published (and partly nonpublished) data on genetic, serologic, and imaging biomarkers for the severity of joint destruction in RA. We evaluated variants in 10 genes (CD40, IL2RA, IL4R, IL15, OPG, DKK1, SOST, GRZB, MMP9, and SPAG16). In 5 variants (IL2RA, DKK1, GRZB, MMP9, and SPAG16), we found evidence of an association at the functional level. We evaluated several serological biomarkers, namely, autoantibodies (RF, ACPA, anti-CarP), markers related to inflammation (ESR, CRP), and proteinases or components of the extracellular matrix of bone and cartilage (MMP3, CTX-I, CTX-II, COMP, TIMP1, PYD, RANKL/OPG, CXCL13). Finally, we evaluated markers that can be visualized by ultrasound or MRI, including erosions, bone marrow edema, synovitis, and tenosynovitis. Several studies showed that bone marrow edema and synovitis on MRI are robust predictors of radiographic progression. Some studies showed that inflammation detected with ultrasound predicted radiographic progression. Future studies will reveal whether adding and combining all these different biomarkers will increase the accuracy of risk models predicting radiographic progression in RA.

Objective.Magnetic resonance imaging (MRI) is increasingly used in rheumatoid arthritis (RA) research. A European League Against Rheumatism (EULAR) task force recently suggested that MRI can improve the certainty of RA diagnosis. Because this recommendation may reflect a tendency to use MRI in daily practice, thorough studies on the value of MRI are required. Thus far no large studies have evaluated the accuracy of MRI to differentiate early RA from other patients with early arthritis. We performed a large cross-sectional study to determine whether patients who are clinically classified with RA differ in MRI features compared to patients with other diagnoses.Methods.In our study, 179 patients presenting with early arthritis (median symptom duration 15.4 weeks) underwent 1.5T extremity MRI of unilateral wrist, metacarpophalangeal, and metatarsophalangeal joints according to our arthritis protocol, the foot without contrast. Images were scored according to OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) by 2 independent readers. Tenosynovitis was also assessed. The main outcome was fulfilling the 1987 American College of Rheumatology (ACR) criteria for RA. Test characteristics and areas under the receiver-operator-characteristic curves (AUC) were evaluated. In subanalyses, the 2010 ACR/EULAR criteria were used as outcome, and analyses were stratified for anticitrullinated protein antibodies (ACPA).Results.The ACR 1987 criteria were fulfilled in 43 patients (24.0%). Patients with RA had higher scores for synovitis, tenosynovitis, and bone marrow edema (BME) than patients without RA (p < 0.05). ACPA-positive patients had more BME (median scores 6.5 vs. 4.25, p = 0.016) than ACPA-negative patients. For all MRI features, the predictive value for the presence of RA was low (< 50%). For all MRI features the AUC were < 0.70. Patients who fulfilled ACR/EULAR 2010 criteria but not ACR87 criteria for RA had less synovitis than patients who were positive for RA according to both sets of criteria (p = 0.029).Conclusion.Although patients with RA had higher scores of MRI inflammation and ACPA-positive patients had more BME, the severity of MRI inflammation assessed according to RAMRIS does not accurately differentiate patients with RA from other early arthritis patients.

Objective.Previous studies indicated that pyridinoline, a collagen crosslink in cartilage and bone, might be a good marker to predict joint destruction in patients with rheumatoid arthritis (RA), although large prospective studies are lacking. We evaluated the predictive value of serum pyridinoline levels for joint destruction, both at baseline for longterm prediction and during the disease course for near-term prediction.Methods.Patients with early RA from the Leiden Early Arthritis Clinic were studied. Radiographs at baseline and yearly during 7 years of followup were scored according to the Sharp-van der Heijde Scoring (SHS) method. Pyridinoline serum levels at baseline and during followup were measured by ELISA. The association between baseline pyridinoline levels and difference in SHS over 7 years was tested, with a multivariate normal regression model. Second, the association between pyridinoline levels determined during the disease course and progression of SHS over the next year was tested with a multivariable linear regression analysis.Results.Studying baseline pyridinoline serum levels in 437 patients revealed that the mean SHS over 7 years was 6% higher for every higher pyridinoline level (nmol/l) at baseline (p = 0.001). Subsequently, during followup (n = 184 patients) the progression in SHS in the upcoming year was 17% higher for every higher nmol/l pyridinoline level (p = 0.001). The area under the receiver-operation characteristic curve for rapid radiological progression was 0.59.Conclusion.Increased pyridinoline serum levels, both at baseline and during the disease course, are associated with more severe joint destruction during the coming year(s), although the predictive accuracy as a sole predictor was moderate.

The objective of this study is to examine the effect of gravity compensation training on reaching and underlying changes in muscle activation. In this clinical trial, eight chronic stroke patients with limited arm function received 18 sessions (30 min) of gravity-compensated reach training (during 6 weeks) in combination with a rehabilitation game. Before and after training, unsupported reach (assessing maximal distance, joint angles and muscle activity of eight shoulder and elbow muscles) and the Fugl-Meyer assessment were compared. After training, the maximal reach distance improved significantly by 3.5 of arm length, together with increased elbow extension (9.2°) and increased elbow extensor activity (68). In some patients, a reduced cocontraction of biceps and anterior deltoid was also involved, although this was not significant on group level. Improvements in unsupported reach after gravity compensation training in chronic stroke patients with mild to severe hemiparesis were mainly accompanied by increased activation of prime movers at the elbow, although in some patients, improved selective joint control may also have been involved. Gravity compensation seems to be a suitable way to provide active, task-specific treatment, without the need for high-tech devices. Further research on a larger scale, including control groups and combinations of arm support with functional hand training, is essential to enhance the potential of arm support to complement poststroke arm rehabilitation.

Background: The aim of this study was to examine whether genetic predisposition to high levels of coagulation factors influences the risk of developing fatal and non‐fatal arterial cardiovascular events in men with a first myocardial infarction (MI). Methods: We performed a cohort study among 542 MI patients with a mean age of 56 years (range 32–70 years) at the time of the event. All of the men had a first MI between 1990 and 1996 and were followed until 1 September 2004. DNA was analyzed for polymorphisms of fibrinogen, prothrombin (factor II), factor V, factor VII and plasminogen activator inhibitor type 1, all of which are associated with gain of function of the protein. We collected information from hospital files and general practitioners on the occurrence of major arterial events. Results: In total, 254 major arterial cardiovascular events occurred during a median follow‐up period of 11 years (range 0.2–15 years). The point estimates of the relative rates (RRs) of these events for the variant genotypes were all between 0.7 and 1.1 except for the prothrombin 20210A mutation: RR 1.8 (95% confidence interval 0.8–4.1). Conclusion: These findings suggest that there is no association between coagulation factor polymorphisms, previously associated with plasma levels, and the risk of recurrent cardiovascular events.

Clavulanic acid (CA) is an important antibiotic that is produced by Streptomyces clavuligerus. CA is unstable and product degradation has turned out to have a major impact on product titers in fed‐batch cultivations. Three different types of experiments have been used to elucidate CA degradation under fed‐batch cultivation conditions. First, the influence of individual medium compounds was examined. Second, degradation was monitored during the exponential growth phase in batch cultivations. Third, CA degradation was studied in the supernatant of samples taken during a fed‐batch. In addition, data from six fed‐batch cultivations were studied to derive information about CA degradation during the production phase. These cultivations were based on a mineral medium, containing glycerol, glutamate, ammonium, and phosphate as the main nutrients. The ammonium concentration had a large influence on the degradation rate constant. In addition, either changes in the substrate availability or high concentrations of ammonium or glycerol cause a major increase in the degradation rate constant. Finally, a linear and a fuzzy logic model were made to predict CA degradation rates in these fed‐batches.

A semi-stoichiometric model has been developed for the clavulanic acid (CA) production by Streptomyces clavuligerus in a fed-batch process on a chemically defined medium. Six fed-batch cultivations were performed with a similar batch medium containing glycerol, glutamate, ammonium and phosphate. Product formation is induced by a stationary phase, and continued within a phosphate limited growth phase by feeding glycerol, phosphate and glutamate and/or ammonium with constant feed rates, or with a varying ammonium addition rate when it is used for pH control. The process can be described well by a stoichiometric model and constant CA production rates for the different metabolic conditions. Only one kinetic function was necessary in the model, i.e., to describe the glutamate uptake rate. The stoichiometric coefficients are estimated from the data and the model parameters are fine-tuned by a genetic algorithm. A fairly simple but accurate model with closed mass balances is obtained.

Streptomyces clavuligerus is a commercially important actinomycete that is used to produce clavulanic acid, a β-lactamase inhibitor. Observations during 10 batch cultivations with S. clavuligerus on defined media have led to the finding that the organism is very sensitive to shear when grown in batch cultures with increasing stirrer speed. The stirrer speed was increased to keep the dissolved oxygen level above 50% air saturation. A quantitative approach based on the calculation of elemental balances and a simple mathematical model is proposed to characterize the biomass lysis. Finally, a linear relation between biomass yield and observed specific growth rate is determined. Results show that cell lysis occurs at a high degradation rate, e.g., μ^max = 0.16 h^-1 and kd = 0.07 h^-1, when the gassed power input increases above 1.1, 1.7, or 2.0 kW/m³, respectively, depending on the medium composition. The overall biomass yield on substrate is dramatically reduced in all experiments (>30%).

Streptomyces clavuligerusis a commercially important actinomycete that is used to produce clavulanic acid, a β‐lactamase inhibitor. Observations during 10 batch cultivations with S. clavuligeruson defined media have led to the finding that the organism is very sensitive to shear when grown in batch cultures with increasing stirrer speed. The stirrer speed was increased to keep the dissolved oxygen level above 50% air saturation. A quantitative approach based on the calculation of elemental balances and a simple mathematical model is proposed to characterize the biomass lysis. Finally, a linear relation between biomass yield and observed specific growth rate is determined. Results show that cell lysis occurs at a high degradation rate, e.g., μmax= 0.16 h−1and kd= 0.07 h−1, when the gassed power input increases above 1.1, 1.7, or 2.0 kW/m3, respectively, depending on the medium composition. The overall biomass yield on substrate is dramatically reduced in all experiments (>30%).

Although exposure to acid water (pH 3.5) induces severe and prolonged reduction in plasma osmolarity and total plasma calcium concentration in tilapia (Oreochromis mossambicus) and goldfish (Carassius auratus), the responses of the hypophyseal cells are clearly different. In tilapia, the size of the rostral pars distalis of the pituitary gland is enlarged as a result of the increase in size and number of prolactin cells. The pars intermedia PAS-positive (PIPAS) cells are not noticeably changed. Conversely, in goldfish, prolactin cells are unaffected, whereas the number of enlarged PIPAS cells increases markedly. Stimulation of prolactin secretion may be responsible for the partial restoration of plasma osmolarity and calcium levels observed in tilapia after two weeks exposure to acid water. Prolactin cells apparently play a role in the adaptation to acid stress by counteracting osmoregulatory disturbances. Goldfish show no restoration of plasma osmolarity during the course of the experiment. Plasma calcium levels tend to increase. Although prolactin may have an osmoregulatory function in goldfish under steady state conditions, goldfish prolactin cells do not seem to participate in the physiological adaptation to environmental changes that disturb water and ion homeostasis. The function of PIPAS cells in tilapia remains unclear and is apparently unconnected with ion regulation. The observations on these cells in goldfish are consistent with the hypercalcemic activity suggested for them.

Recent contributions to the literature on urban economic theory focus mainly on the relations between changes in the organization of firms and the spatial restructuring of urban regions. In this respect, it is argued that changes in the production system result in new locational preferences of firms and consequently in changes in the spatial pattern of cities. In this paper we stress the relevance of both shifts in the organization of firms and markets with respect to urban spatial restructuring processes, but at the same time we notice an important shortcoming in this theoretical tradition: processes that are being held responsible for the provision of the built environment - the way in which the urban spatial structure is actually changed - are generally neglected. The interconnectedness of these different processes is demonstrated empirically in a case study of developments that took place in the region Noordoost-Brabant. It is concluded that institutional urban economic theory is only partially able to explain the observed developments. The dynamics of urban economic growth and the processes that underlie property market functioning should be studied in relation to each other.

Early prostate cancer detection and treatment are of major importance to reduce mortality rate. magnetic resonance (MR) imaging provides images of the prostate where an early stage lesion can be visualized. The use of robotic systems for MR-guided interventions in the prostate allows us to improve the clinical outcomes of procedures such as biopsy and brachytherapy. This work presents a novel MR-conditional robot for prostate interventions. The minimally invasive robotics in an magnetic resonance imaging environment (MIRIAM) robot has 9 degrees-of-freedom (DoF) used to steer and fire a biopsy needle. The needle guide is positioned against the perineum by a 5 DoF parallel robot driven by piezoelectric motors. A 4 DoF needle driver inserts, rotates and fires the needle during the procedure. Piezoelectric motors are used to insert and rotate the needle, while pneumatic actuation is used to fire the needle. The MR-conditional design of the robot and the needle insertion controller are presented. MR compatibility tests using T2 imaging protocol are performed showing a SNR reduction of 25% when the robot is operational within the MR scanner. Experiments inserting a biopsy needle toward a physical target resulted in an average targeting error of 1.84mm. Our study presents a novel MR-conditional robot and demonstrated the ability to perform MR-guided needle-based interventions in soft-tissue phantoms. Moreover, the image distortion analysis indicates that no visible image deterioration is induced by the robot.

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It was established some time ago that the deletion of base C1054 in E.coli 16S rRNA specifically affects UGAdependent termination of translation. Based on this observation, a model for the termination event was proposed in which the UGA nonsense codon on the mRNA base-pairs with a complementary motif in 'helix 34' of the 16S rRNA, thus potentially providing a recognition signal for the binding of the release factor. This model has been re-examined here and evidence is presented which demonstrates that ribosomes containing the C1054A mutation enhance the activity of suppressors of both UAG and UAA termination codons introduced into the host. The results do not support the nonsense codon-16S rRNA base pairing model, and rather imply a more general involvement of 'helix 34' in the translation termination reactions.