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Recent events, such as the COVID-19 pandemic, have drawn nationwide attention to systemic racism as a serious threat to public health in Canada. One promising approach to address such racism is through developing and implementing standardized procedures for collecting and using disaggregated, race-based data. In this commentary, we summarize why this approach is necessary to address systemic racism in Canada, and highlight municipal actions being taken in Edmonton, Alberta, to move this approach forward. In 2021, a Race-based Data Table, comprising 24 institutions and organizations affiliated with health, education, and policing systems, was formed in Edmonton. It aimed to engage practitioners, systems representatives, academics, and community members in collective advocacy around accessing race-based data to better understand and address disparate health outcomes associated with COVID-19 for racialized communities. Further, the Table intends to co-create a charter and toolkit outlining best practices for ethical, race-based data collection and use with local stakeholders and knowledge users. In documenting the beginning stages of the Table, and in evaluating its ongoing progress, we contribute to national conversations regarding the need for government institutions and other organizations to consistently collect and use race-based data as a means of increasing transparency and accountability in their actions.

The deep understanding of the behaviors of traffic participants is essential to guarantee the safety of automated vehicles (AV) in mixed traffic with vulnerable road users (VRUs). Precise trajectory prediction of traffic participants can provide reasonable solution space for motion planning of AV. Early works mainly focused on handcrafting the feature representation and designing complicated architectures in deep learning-based prediction models. However, these approaches overlooked the fact that different road users perceive the safety of the same interaction differently and also exhibit heterogeneous risk-taking styles. In this paper, we will develop a model for trajectory prediction based on risk-taking styles. The model accounts for the expected positions and occupancy of traffic participants in the surrounding environment. It consists of two sequential steps: risk-taking styles of multi-modal road users under interactive scenes are first clustered, and then reformulated in the heterogeneous graph model for trajectory prediction. The model is validated by the driving data collected on the urban road using a public dataset. Comparative experiments demonstrate that the proposed method can predict the trajectory of traffic participants much more accurately than the state-of-the-art methods.

ABSTRACTSeveral ethnic groups in Thailand consider themselves oppressed; arguably, Thai society lacks suitable platforms for multiple voices and perspectives. Vivid Ethnicity, a mobile museum constituted by Mahidol University, addresses this issue. Adapting Kenneth Burke’s concept of the “dramatistic pentad,” communication theory, and the concept of transformative learning developed by Jack Mezirow, Vivid Ethnicitycreates a theory of exhibition geared toward critical thinking and creative praxis. Ethnographic performances combined with participatory workshops are shown to be key factors in opening up conversations and encouraging audience to construct their own meaning.

The main limitation to long-term lung transplant (LT) survival is chronic lung allograft dysfunction (CLAD), which leads to irreversible lung damage and significant mortality. Individual factors can impact CLAD, but no large genetic investigation has been conducted to date. We established the multicentric Genetic COhort in Lung Transplantation (GenCOLT) biobank from a rich and homogeneous sub-part of COLT cohort. GenCOLT collected DNA, high-quality GWAS (genome-wide association study) genotyping and robust HLAdata for donors and recipients to supplement COLT clinical data. GenCOLT closely mirrors the global COLT cohort without significant variations in variables like demographics, initial disease and survival rates (P> 0.05). The GenCOLT donors were 45 years-old on average, 44% women, and primarily died of stroke (54%). The recipients were 48 years-old at transplantation on average, 45% women, and the main underlying disease was chronic obstructive pulmonary disease (45%). The mean follow-up time was 67 months and survival at 5 years was 57.3% for the CLAD subgroup and 97.4% for the non-CLAD subgroup. After stringent quality controls, GenCOLT gathered more than 7.3 million SNP and HLA genotypes for 387 LT pairs, including 91% pairs composed of donor and recipient of European ancestry. Overall, GenCOLT is an accurate snapshot of LT clinical practice in France and Belgium between 2009 and 2018. It currently represents one of the largest genetic biobanks dedicated to LT with data available simultaneously for donors and recipients. This unique cohort will empower to run comprehensive GWAS investigations of CLAD and other LT outcomes.

Biliary leakage is a serious complication after liver resection and represents the major cause of post-operative morbidity. In spite of already identified risk factors, little is known about the role of intra-biliary pressure following liver surgery in the development of biliary leakage. Biliary decompression may have a positive impact and reduce the incidence of biliary leakage at the parenchymal resection site. 397 patients undergoing liver resection without bilioenteric anastomosis were included in the retrospective analysis of the risk factors for the development of biliary leakage focusing on the intra-operative reduction of the biliary pressure by T-tube and liver histology. Among 397 analyzed patients after parenchymal resection, biliary leakage occurred in 39 cases (9.8 %). The extent of parenchymal resection was not associated with the total occurrence of biliary leak (p= 0.626). Lower incidence of biliary leakage from the resection surface was significantly associated with the use of T-tube (4.9 vs. 13.2 %; p= 0.006). In the subgroup analysis, insertion of a T-tube was not associated with a reduction of biliary leakage after anatomical hemihepatectomies (p= 0.103) and extraanatomical liver resection (p= 0.676). However, a high statistical significance could be detected in patients with extended hemihepatectomies (58.3 vs. 3.8 %; p< 0.001). Once biliary leak occurred without T-tube, median hospitalization duration significantly increased compared to patients with biliary decompression and without biliary leak (p< 0.001). The results of our retrospective data analysis suggest a significant beneficial impact of the T-tube on the development of biliary leakage in patients undergoing extended liver surgery.

The pre-insertion process called anticipation is an essential component of a lane-changing manoeuvre. There is little empirical research regarding the impact of anticipation. Thus, this paper aims to explore the behaviour of the new follower (NF) in the target lane when it encounters anticipation by using new trajectory datasets. The changing magnitude of the reaction pattern is proposed to identify the NF’s behaviour. We find that the anticipation significantly affects the NF’s movement in terms of gap creation and speed reduction. Then, we conduct a detailed analysis of critical variables to reveal their relationship with the NF’s behaviour. Following this, we develop binary logistic models to predict the NF’s behaviour, resulting in a good performance. It also suggests that the NF’s behaviour is highly related to the anticipation-related variables. The transferability test results show that this model can be directly used in different locations and times with satisfactory accuracy.

Traffic dynamics on freeways are stochastic in nature because of errors in perception and operation of drivers as well as the heterogeneity between and within drivers. This stochasticity is often represented in car-following models by a stochastic term, which is assumed to follow a normal distribution for the convenience of mathematical processing. However, the validity of this assumption has not been studied yet. In this study, we focused on the shape of the distribution of a stochastic term in the car-following model that predicts an acceleration after a time step. Based on vehicle trajectory data on a freeway in Japan, a car-following model is first developed by using data-driven methodology in which long short-term memory (LSTM) network is applied. In this LSTM network, the acceleration value is discretized and the model parameters are trained with the focal loss function. The relationship between the predicted distributions’ modality, standard deviation (SD), and IAwith respect to traffic states is then examined. The findings demonstrate that: 1) the developed model can accurately predict the accelerations; 2) a probabilistic distribution tends to have a large SD and multimodality around a merging point and at the beginning of and along stop-and-go waves; and 3) driving behavior can be classed in one of four clusters based on the variation of the percentile value that a driver takes within the probability distribution. The proposed model and the insights are helpful for improving microscopic simulation models when considering new traffic management measures.

The present study focuses on the synthesis and characterization of lanthanide-containing paramagnetic ionic liquids (ILs), [CnC1Im]3[MCl3X3] (n= 4, 6, and 8; M = Gd, Dy, and Ho; X = Br and Cl), derived from 1-alkyl-3-methylimidazolium anions. These paramagnetic ILs exhibit low vapor pressure, high thermal stability, physiochemical stability, and tunability, along with significant magnetic susceptibility, making them of interest in advanced material applications that may take advantage of neat liquids with magnetic susceptibility. Structural and physical properties were determined using FTIR, 1H NMR, DSC, and TGA. The room temperature density and viscosity of the iron paramagnetic ILs were also reported. Accompanying this report of paramagnetic IL products, we reintroduce and highlight Evan’s NMR technique, an accessible magnetic susceptibility measurement technique that can utilize any available proton NMR to characterize the magnetic susceptibility of ILs. This work demonstrates the robustness of Evan’s technique by demonstrating the ability to account for the IL water content, a common issue for hygroscopic materials, during the measurement of magnetic susceptibility. A detailed comparison of the ILs is presented, with dysprosium- and holmium-containing paramagnetic ILs exhibiting the highest magnetic susceptibility reported for mononuclear ILs reported to date. These materials have been studied with an eye on applications for mass transfer, eventually seeking to optimize magnetic susceptibility and viscosity using magnetic field gradients to move paramagnetic ILs carrying solute or heat. The study of paramagnetic ILs is important not only for understanding the magnetic properties of these materials but also for potential applications in areas such as magnetic resonance imaging, biomedicine, environmental remediation, and mass transfer. These unique materials have the potential to bring about new advances and technologies in the fields of materials science and analytical chemistry.

Background and aims: With an external additional working channel (AWC) endoscopic mucosal resection (EMR) as well as endoscopic submucosal dissection (ESD) can be extended to techniques termed “EMR+” and “ESD+.” These novel techniques are systematically compared to EMR and ESD under the use of a double-channel endoscope (DC). Methods: Our trial was conducted prospectively in a pre-clinical porcine animal model (EASIE-R simulator) with standardized gastric lesions measuring 3 or 4 cm. Results: EMR+ and EMR DC showed both good results for 3 cm lesions with no adverse events and an en bloc resection rate of 73.33% (EMR+) and 60.00% (EMR DC, p= 0.70). They came to their limits in 4 cm lesions with muscularis damages of 20.00% (EMR+), 13.33% (EMR DC, p≥ 0.99) and decreasing en bloc resection rates of 60.00% (EMR+) and 46.67% (EMR DC, p= 0.72). Conclusions: With the AWC, a standard endoscope can easily be transformed to double-channel functionality. We could show that EMR+ and ESD+ are non-inferior to EMR and ESD under the use of a double-channel endoscope. Consequently, the AWC presents an affordable alternative to a double-channel endoscope for both EMR and ESD.

Path dispersion (the spatial distribution of vehicular paths) is an important feature of traffic flow inside intersections and differs from traffic flow running along traffic lanes at road segment, especially under conflicting movements. The path dispersion reflects the operational features of traffic flow and is related to driving behaviour, arrival flow patterns, layout design, and the traffic control and management scheme. This study aims to improve the understanding of the overall path dispersion of unprotected left-turns and the opposing through movement. A behavioural simulation model was established to represent the overall path dispersion. Human behaviours regarding vehicle trajectory planning with and without conflicting vehicles were modelled based on optimal control and integrated into the proposed discrete event simulation framework. The descriptive power and accuracy of the proposed simulation model were validated using empirical data. The effects of the spatial size of the intersection, crossing angle, and traffic volume on the path dispersion of the left-turn and through movement were explored based on numerical experiments. The results show that the proposed simulation model can represent the path dispersion of left-turn and opposing through movement well for both the calibrated intersections and newly added intersections without model parameter recalibration with an average error of 8.92%.

ABSTRACTBackgroundTo examine safety and efficacy of tezacaftor-ivacaftor (TEZ/IVA) in a real-life setting in adults living with cystic fibrosis.MethodsA multicentre retrospective observational study, including adults living with cystic fibrosis (pwCF) eligible for TEZ/IVA, with assessments at baseline, 3 months (visit3mo) and 6 months (visit6mo) after start of treatment. Outcomes included change in FEV1, LCI, FeNO, CFQ-R, estimated number of annual acute exacerbations, BMI, dosage of pancreatic enzyme replacement therapy (PERT) and airway microbiology. We also assessed safety.ResultsForty-eight adult pwCF (mean (±SD) age 33 (±12) years; mean FEV165 (±19) %P) were included. Three subgroups were identified: pwCF F/F CFTR modulator-naive (n = 28; 58%), pwCF F/F previously treated with lumacaftor-ivacaftor (n = 11; 23%) and pwCF F/RF (n = 9; 19%). Adverse events were described in 3 pwCF (6%) during the 6-month observation period (in one leading to treatment interruption). At visit3mo,FEV1had improved in all subgroups. In the entire group, mean FEV1had increased from 66 (±2.9) %P to 72 (±2.9) %P (p < 0.0001). Similarly, LCI improved by approximately one unit at visit3mo(p = 0.02). At visit6momean annual acute exacerbation rate decreased significantly (p = 0.02). Only in the CFQ-R social functioning domain score, a significant improvement was observed at visit6mo(p < 0.01).ConclusionsWe showed that TEZ/IVA is safe, well tolerated and effective in terms of improvement of lung function, ventilation inhomogeneity, health-related social functioning, and reduction of estimated annual acute exacerbation rate, in adult pwCF F/F and F/RF. Results in this real-life study reflect those observed in RCTs.

ABSTRACTSpectrally and spatially resolved information on daylight is critically important when planning for non-image forming (NIF) responses. Nevertheless, the availability of such data is scarce given the high initial costs and complex on-site maintenance of high-end spectral measurement devices. The CIE (Commission Internationale de l’Éclairage) reconstruction procedure allows for the derivation of the daylight spectral power distribution (SPD) from the chromaticity coordinates or the correlated color temperature (). However, several studies have suggested that both the daylight locus and the reconstruction procedure are erroneous, and specifically SPDs with a higher cannot be reproduced accurately.This paper studies the reconstruction accuracy of the SPD of daylight, and contextualizes the findings in relation to NIF effects. The analysis comprises a comparative study to determine the accuracy of the CIE procedure compared to two localized reconstruction procedures, and a sensitivity study to examine the impact of accuracy on the assessment of NIF responses, as represented by all five retinal photoreceptors and expressed in the α-opic efficacy of luminous radiation. The results indicated that a localized procedure, adjusting both the daylight locus and the PCA components of daylight, outperformed the CIE reconstruction method. However, improvement in the reconstruction accuracy had no effect on NIF assessment. The RSMPE for α-opic quantities did not exceed 4% for any procedure. In practical terms, this implies that cost-effective sensors and the representation of spectral properties in sky models with a single value – the correlated color temperature – can be used for NIF purposes. These findings bridge theory and practice by opening up new insights into the understanding of simplified methods used to determine NIF effects of daylight.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive–behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which ‘downgraded’ the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

We study the origin and formation of antiphase domains (APDs) and related defects in 7 nm thin, lattice-matched GaP buffer layers deposited by metal–organic chemical vapor deposition (MOCVD) on well-defined, nearly single-domain, double-layer stepped, low-miscut Si(100) substrates obtained by specific treatment with arsenic. Using dark-field imaging modes in low-energy electron microscopy (LEEM), the minority reconstruction domains of Si(100):As and the APDs of the deposited GaP epilayer are identified, quantified, and compared. We show that residual (2 × 1)-reconstructed terraces of the minority domain on the Si substrate cause the formation of APDs and that the fraction of the minority domain of the substrate (≅0.07) entails a comparable fraction of APDs in thin GaP epilayers. The topographies of APDs are revealed by atomic force microscopy (AFM) and by scanning tunneling microscopy (STM). We observe two very different APD-related defects in the GaP epilayer, both pinned to residual monolayer steps of the substrate. GaP growth on minority domain terraces with widths in the range of 40–100 nm gives rise to APDs of comparable lateral dimensions. Minority domain terraces of the substrate with widths <20 nm cause the formation of 7–20 nm wide trenches in the GaP layer with rampart-like mounds along their rims. Using nanoscale Auger electron spectroscopy (AES), we provide evidence that these trenches extend through the GaP layer down to the exposed, uncovered Si substrate. We conclude that nucleation of GaP on small minority domain terraces is largely inhibited as most Ga and P atoms deposited on these terraces diffuse across the domain boundary and side walls of emerging trenches to adjacent majority domain terraces where they form the observed mounds. Nucleation of GaP does take place on minority domain terraces with widths ≥40 nm and leads to the growth of APDs.

In patients with interstitial lung disease (ILD) complicating classical or amyopathic idiopathic inflammatory myopathy (IIM), lung transplantation outcomes might be affected by the disease and treatments. Here, our objective was to assess survival and prognostic factors in lung transplant recipients with IIM-ILD. We retrospectively reviewed data for 64 patients who underwent lung transplantation between 2009 and 2021 at 19 European centers. Patient survival was the primary outcome. At transplantation, the median age was 53 [46–59] years, 35 (55%) patients were male, 31 (48%) had classical IIM, 25 (39%) had rapidly progressive ILD, and 21 (33%) were in a high-priority transplant allocation program. Survival rates after 1, 3, and 5 years were 78%, 73%, and 70%, respectively. During follow-up (median, 33 [7–63] months), 23% of patients developed chronic lung allograft dysfunction. Compared to amyopathic IIM, classical IIM was characterized by longer disease duration, higher-intensity immunosuppression before transplantation, and significantly worse posttransplantation survival. Five (8%) patients had a clinical IIM relapse, with mild manifestations. No patient experienced ILD recurrence in the allograft. Posttransplantation survival in IIM-ILD was similar to that in international all-cause-transplantation registries. The main factor associated with worse survival was a history of muscle involvement (classical IIM). In lung transplant recipients with idiopathic inflammatory myopathy, survival was similar to that in all-cause transplantation and was worse in patients with muscle involvement compared to those with the amyopathic disease.

In patients with interstitial lung disease (ILD) complicating classical or amyopathic idiopathic inflammatory myopathy (IIM), lung transplantation outcomes might be affected by the disease and treatments. Here, our objective was to assess survival and prognostic factors in lung transplant recipients with IIM‐ILD. We retrospectively reviewed data for 64 patients who underwent lung transplantation between 2009 and 2021 at 19 European centers. Patient survival was the primary outcome. At transplantation, the median age was 53 [46–59] years, 35 (55%) patients were male, 31 (48%) had classical IIM, 25 (39%) had rapidly progressive ILD, and 21 (33%) were in a high‐priority transplant allocation program. Survival rates after 1, 3, and 5 years were 78%, 73%, and 70%, respectively. During follow‐up (median, 33 [7–63] months), 23% of patients developed chronic lung allograft dysfunction. Compared to amyopathic IIM, classical IIM was characterized by longer disease duration, higher‐intensity immunosuppression before transplantation, and significantly worse posttransplantation survival. Five (8%) patients had a clinical IIM relapse, with mild manifestations. No patient experienced ILD recurrence in the allograft. Posttransplantation survival in IIM‐ILD was similar to that in international all‐cause‐transplantation registries. The main factor associated with worse survival was a history of muscle involvement (classical IIM). In lung transplant recipients with idiopathic inflammatory myopathy, survival was similar to that in all‐cause transplantation and was worse in patients with muscle involvement compared to those with the amyopathic disease. A retrospective multicenter study shows that patient survival after lung transplantation for myositis‐related interstitial lung disease is comparable to that reported in international registries for all causes combined.

Traffic jams are caused by a traffic demand that exceeds road capacity. Road capacity, therefore, is an important road feature. This capacity might change as function of time, even for the same road stretch, owing to changing driving behaviors or vehicle characteristics. In this study, we empirically analyzed the changes in road capacity over a 5- to 10-year period. The study differentiated between free flow capacity and queue discharge rate. We used three road stretches that remained unchanged to study free flow capacity. For 143 other locations that experienced changing properties over time, we analyzed queue discharge rates and corrected for external changes. We found that free flow capacity decreased, and queue discharge rates (slightly) increased over time. It is remarkable that one decreased, whereas the other increased. These results could be used in policies for road planning and design. Moreover, they provide an interesting background for further studies analyzing the effects of particular behavioral changes or driver assistance systems.

AbstractLocal cultural heritage is now recognised as a factor in locational attractiveness and quality of life. Cultural heritage can also strengthen a sense of place, which can be a prerequisite for empowering citizens for sustainability transformations. Nevertheless, the specific cultural heritage of small and medium-sized towns is underrepresented in common surveys and policies. This article traces the collaborative development of regional and local strategies for the protection and valorisation of built cultural heritage in the German-Polish border region. The basis for these strategies were five hypotheses that brought together knowledge about development dynamics in small and medium-sized towns, their specific quality of life and aspects of cultural heritage. These hypotheses were discussed and reflected upon in the ten German and Polish towns and condensed into location-specific approaches.

Pedestrians are among the travelers most vulnerable to collisions that are associated with high fatality and injury rates. The increasing rate of urbanization and mixed land-use construction make walking (along with other non-motorized travel) a predominant transportation mode with a wide variety of behaviors expected. Because of the inherent safety concerns seen in pedestrian transportation infrastructures, especially those with conflicting multimodal movements expected (crosswalks, transit platforms, etc.), it is important that pedestrian behavior is modeled as a risk-taking stochastic behavior that may lead to errors and thus collision formation. In previous work, the complexity and cost associated with building pedestrian models in a cognitive-based environment weighted down the construction of simulation tools that can capture pedestrian-involved collisions, including those seen in shared space environments. In this paper, a tool that will help evaluate the safety of pedestrian traffic is initiated: an extended modeling framework of pedestrian walking behavior is adopted while incorporating different physiological, physical, and decision-making elements. The focus is on operational decisions (i.e., path choices defined by longitudinal and lateral trajectories) with a pre-specified set of origins and destinations. The model relies on the prospect theory paradigm where pedestrians evaluate their acceleration and directional alternatives while considering the possibility of colliding with other “particles.” Using a genetic algorithm method, the new model is calibrated using detailed trajectory data. This model can be extended to model the interactions between a variety of different modes that are present in different mixed land-use environments.

Soziale Arbeit gilt als ein fester Bestandteil der medizinischen Rehabilitation. Allerdings bestehen bisher unerklärbare Variationen hinsichtlich der Ausgestaltung und Inanspruchnahme ihrer Leistungen sowie Hinweise auf negative Effekte sozialarbeiterischer Leistungen in der medizinischen Rehabilitation. Zudem wurden die theoretischen Grundlagen der Tätigkeiten von Sozialarbeiter*innen in der Rehabilitation bisher nicht ausreichend expliziert. Das in diesem Beitrag vorgestellte Forschungsprojekt „Sozialarbeiterische Wirkmechanismen in der medizinischen Rehabilitation“ (SWIMMER) setzt hier an. Nach einer Erläuterung des Settings der medizinischen Rehabilitation, der Rolle der Sozialen Arbeit in diesem und des methodischen Vorgehens wird das Projekt, dessen Ziele die Erklärung der Variationen und die Entwicklung einer Programmtheorie Sozialer Arbeit in der medizinischen Rehabilitation sind, konzeptionell und theoretisch eingeordnet. Bezugspunkte dieser Auseinandersetzung sind das Tripelmandat, die Theorie Sozialer Arbeit als Wissenschaft und Praxis der Erklärung, Lösung und Vorbeugung sozialer Probleme, die Rehabilitationswissenschaften mit einem Fokus auf der Rehabilitation als Gesundheitsstrategie, die Perspektive der Versorgungsforschung und „evidence-based practice“. Darauf aufbauend werden die Vorannahmen des Projekts dargelegt.

Long‐term survival after lung transplantation is limited by chronic allograft dysfunction. The aim of this study was to investigate the effect of locally augmented immunosuppression with liposomal cyclosporine A for inhalation (L‐CsA‐i) for the prevention of bronchiolitis obliterans syndrome (BOS). In a randomized, double‐blind, placebo‐controlled, multi‐center Phase 3 study, 180 LT recipients in BOS grade 0 were planned to receive L‐CsA‐i or placebo in addition to triple‐drug immunosuppression. L‐CsA‐i was administered twice daily via an Investigational eFlow nebulizer to recipients of single (SLT) and bilateral lung transplants (BLT) within 6–32 weeks posttransplant, and continued for 2 years. The primary endpoint was BOS‐free survival. 130 patients were enrolled before the study was prematurely terminated for business reasons. Despite a 2‐year actuarial difference in BOS‐free survival of 14.1% in favor of L‐CsA‐i in the overall study population, the primary endpoint was not met (p= .243). The pre‐defined per protocol analysis of SLT recipients (n = 24) resulted in a treatment difference of 58.2% (p= .053). No difference was observed in the BLT (n= 48) subpopulation (p= .973). L‐CsA‐i inhalation was well tolerated. Although this study failed to meet its primary endpoint, the results warrant additional investigation of L‐CsA‐i in lung transplant recipients. In lung transplant recipients, augmentation of local immunosuppression with inhaled liposomal cyclosporine A to prevent bronchiolotis obliterans syndrome is safe and potentially effective in delaying loss of lung function. Iacono comments on page 9.

Long-term survival after lung transplantation is limited by chronic allograft dysfunction. The aim of this study was to investigate the effect of locally augmented immunosuppression with liposomal cyclosporine A for inhalation (L-CsA-i) for the prevention of bronchiolitis obliterans syndrome (BOS). In a randomized, double-blind, placebo-controlled, multi-center Phase 3 study, 180 LT recipients in BOS grade 0 were planned to receive L-CsA-i or placebo in addition to triple-drug immunosuppression. L-CsA-i was administered twice daily via an Investigational eFlow nebulizer to recipients of single (SLT) and bilateral lung transplants (BLT) within 6–32 weeks posttransplant, and continued for 2 years. The primary endpoint was BOS-free survival. 130 patients were enrolled before the study was prematurely terminated for business reasons. Despite a 2-year actuarial difference in BOS-free survival of 14.1% in favor of L-CsA-i in the overall study population, the primary endpoint was not met (p= .243). The pre-defined per protocol analysis of SLT recipients (n = 24) resulted in a treatment difference of 58.2% (p= .053). No difference was observed in the BLT (n= 48) subpopulation (p= .973). L-CsA-i inhalation was well tolerated. Although this study failed to meet its primary endpoint, the results warrant additional investigation of L-CsA-i in lung transplant recipients.

Freeway on-ramp areas are susceptible to traffic congestion during peak hours. To delay or prevent the onset of congestion, ramp metering can be applied. A Ramp Metering Installation (RMI) controls the inflow from the on-ramp to the main line so that the total flow can be kept just below capacity. Current ramp metering algorithms apply macroscopic traffic characteristics, which do not entirely prevent inefficient merging behavior from occurring. This paper presents a microscopic ramp metering approach based on gap detection in the right-hand lane of the main line. As preparation for the analyses, trajectory data were collected, by which the mean and standard deviation of driver accelerations were calculated. Simulation, including driver acceleration, is used to test the ramp metering controller. Overall, it shows travel-time savings compared with no-control and compared with existing macroscopic ramp metering systems. Especially during periods of very high main line demand, the microscopic control approach is able to achieve additional travel-time savings. This way, the proposed algorithm can contribute to more efficient road usage and shorter travel times.

Traffic flow might be limited by cross-traffic which has priority. A typical example of such a situation is a location where cyclists or pedestrians cross a stream of car traffic. Splitting the cross-traffic into two separate sub-streams (for instance left–right and right–left) can increase the capacity of the main stream. This is because it is no longer necessary to have a sufficiently large gap in both sub-streams simultaneously. This paper introduces a method to compute the resulting capacity of roads with cross-traffic. Without loss of generality, we introduce three transformations to simplify computations. These transformations are an important contribution of the paper, allowing us to create scalable graphs for capacity. Overall, the research shows that splitting a crossing stream into two equally large sub-streams increases the capacity of the main stream. If there is place for one vehicle in between two sub-streams, the capacity can increase up to threefold. Even larger gains are possible with more vehicles in between. This paper presents graphs which can be used to find the capacity for generic situations, and can be used for developing guidelines on intersection design.

Graphical abstract:

Traffic engineers rely on microscopic traffic models to design, plan, and operate a wide range of traffic applications. Recently, large data sets, yet incomplete and from small space regions, are becoming available thanks to technology improvements and governmental efforts. With this study we aim to gain new empirical insights into longitudinal driving behavior and to formulate a model which can benefit from these new challenging data sources. This paper proposes an application of an existing formulation, Gaussian process regression (GPR), to describe individual longitudinal driving behavior of drivers. The method integrates a parametric and a non-parametric mathematical formulation. The model predicts individual driver’s acceleration given a set of variables. It uses the GPR to make predictions when there exists correlation between new input and the training data set. The data-driven model benefits from a large training data set to capture all driver longitudinal behavior, which would be difficult to fit in fixed parametric equation(s). The methodology allows us to train models with new variables without the need of altering the model formulation. And importantly, the model also uses existing traditional parametric car-following models to predict acceleration when no similar situations are found in the training data set. A case study using radar data in an urban environment shows that a hybrid model performs better than parametric model alone and suggests that traffic light status over time influences drivers’ acceleration. This methodology can help engineers to use large data sets and to find new variables to describe traffic behavior.

The European OPTIMISTIC clinical trial has demonstrated a significant, yet heterogenous effect of Cognitive Behavioural Therapy (CBT) for Myotonic Dystrophy type 1 (DM1) patients. One of its remaining aims was the assessment of efficacy and adequacy of clinical outcome measures, including the relatively novel primary trial outcome, the DM1-Activ-c questionnaire. Assessment of the relationship between the Rasch-built DM1-Activ-c questionnaire and 26 commonly used clinical outcome measurements. Identification of variables associated with CBT response in DM1 patients. Retrospective analysis of the to date largest clinical trial in DM1 (OPTIMISTIC), comprising of 255 genetically confirmed DM1 patients randomized to either standard care or CBT with optionally graded exercise therapy. Correlations of 27 different outcome measures were calculated at baseline (cross-sectional) and of their respective intervention induced changes (longitudinal). Bootstrap enhanced Elastic-Net (BeEN) regression was validated and implemented to select variables associated with CBT response. In cross-sectional data, DM1-Activ-c correlated significantly with the majority of other outcome measures, including Six Minute Walk Test and Myotonic Dystrophy Health Index. Fewer and weaker significant longitudinal correlations were observed. Nine variables potentially associated with CBT response were identified, including measures of disease severity, executive cognitive functioning and perceived social support. The DM1-Activ-c questionnaire appears to be a well suited cross-sectional instrument to assess a variety of clinically relevant dimensions in DM1. Yet, apathy and experienced social support measures were less well captured. CBT response was heterogenous, requiring careful selection of outcome measures for different disease aspects.

Background and aims: A new external additional working channel (AWC) was recently introduced by which endoscopic submucosal dissection (ESD) can be converted to a technique termed “ESD+ ”. We aim to systematically evaluate this novel technique in flat gastric lesions and compare it to classical ESD. Methods: The study was prospectively conducted in a pre-clinical ex vivo animal model (EASIE-R simulator) with porcine stomachs. Prior to intervention, we set standardized lesions measuring 3 cm or 4 cm in antegrade as well as in retrograde positions. Results: Overall, 64 procedures were performed by an experienced endoscopist. Both techniques were reliable and showed en bloc resection rates of 100%. Overall, ESD+ reduced time of procedure compared to ESD (24.5 vs. 32.5 min, p= 0.025*). Particularly, ESD+ was significantly faster in retrograde lesions with a median of 22.5 vs. 34.0 min in 3 cm retrograde lesions (p= 0.002*) and 34.5 vs. 41.0 min (p= 0.011*) in 4 cm retrograde lesions. There were 0 perforations with both techniques. In ESD+ , 1 muscularis damage occurred (3.13%) compared to 6 muscularis damages with ESD (18.75%, p= 0.045*). Conclusions: By its grasp-and-mobilize technique, ESD+ allows potentially faster and safer resections of flat gastric lesions compared to conventional ESD in an ex vivo porcine model. The potential advantages of ESD+ in terms of procedure time may be particularly relevant for difficult lesions in retrograde positions.

Antibiotic underdosing in prophylactic antibiotic regimes after lung transplantation (LTx) can increase the risk of infection. We aimed to study whether β‐lactam concentrations achieved desirable pharmacodynamic targets in the early phase after LTx and the association between drug concentrations and the development of early infections or the acquisition of multidrug‐resistant (MDR) strains. We reviewed patients in whom broad‐spectrum β‐lactam levels were measured after LTx during antibiotic prophylaxis. β‐Lactam concentrations were considered “insufficient” if drug levels remained below four times the clinical breakpoint of the minimal inhibitory concentration for Pseudomonas aeruginosa. The primary outcome was the occurrence of an infection and/or acquisition of MDR pathogens in the first 14 days after transplantation. A total of 70 patients were included. “Insufficient” drug concentrations were found in 40% of patients. In 27% of patients, an early MDR pathogen was identified and 49% patients were diagnosed with an early posttransplant infection. Patients with “insufficient” drug concentrations acquired more frequently MDR bacteria and/or developed an infection than others (22/28, 79% vs. 20/42, 48% – p= .01). β‐Lactam levels were often found to be below the desired drug targets in the early phase after transplantation and may be associated with the occurrence of early infectious complications. Lung transplant recipients with insufficient β‐lactam concentrations more frequently acquire multi‐drug resistant bacteria and/or develop an infection.

Antibiotic underdosing in prophylactic antibiotic regimes after lung transplantation (LTx) can increase the risk of infection. We aimed to study whether β-lactam concentrations achieved desirable pharmacodynamic targets in the early phase after LTx and the association between drug concentrations and the development of early infections or the acquisition of multidrug-resistant (MDR) strains. We reviewed patients in whom broad-spectrum β-lactam levels were measured after LTx during antibiotic prophylaxis. β-Lactam concentrations were considered “insufficient” if drug levels remained below four times the clinical breakpoint of the minimal inhibitory concentration for Pseudomonas aeruginosa. The primary outcome was the occurrence of an infection and/or acquisition of MDR pathogens in the first 14 days after transplantation. A total of 70 patients were included. “Insufficient” drug concentrations were found in 40% of patients. In 27% of patients, an early MDR pathogen was identified and 49% patients were diagnosed with an early posttransplant infection. Patients with “insufficient” drug concentrations acquired more frequently MDR bacteria and/or developed an infection than others (22/28, 79% vs. 20/42, 48% – p= .01). β-Lactam levels were often found to be below the desired drug targets in the early phase after transplantation and may be associated with the occurrence of early infectious complications.

ABSTRACTThe growing demand for food, water, and shelter change the way people use land. These changes have affected or even caused conflict in several locations. However, conflicts do not erupt in isolation; they are the result of multiple interacting causes. There is limited structural understanding of these causes. In this study, we systematically coded case studies that report on conflict related to land-use change, including deforestation in commodity frontiers, agricultural development on common land, and urban development. Based on an analysis of 62 cases, we identified population growth, overlapping land rights, ethnic fragmentation, and economic inequality as the most frequently reported root causes, while rises in land prices was the most often reported proximate cause. Reported institutional causes suggest that the problem is not necessarily the complete absence of governance mechanisms, but rather that governance mechanisms are not fully equipped to deal with the complexities of the observed land-use changes.

Bicycles are gaining popularity as a mode of transport resulting in a mixed bicycle–car traffic situation on urban roads. Cyclists, however, are hardly included in traffic flow models which complicates the design of safe and congestion-free traffic situations. This work introduces class-specific speed functions based on two variables, being space headway for both cars and cyclists. This enables the macroscopic modelling of mixed bicycle–car traffic. The multi-class macroscopic flow model is successfully tested for different traffic situations that occur on urban roads where cyclists and cars share the same infrastructure, e.g. cyclists overtaking a queue of cars and cars overtaking cyclists with reduced speed. The mixed bicycle–car flow model allows travel time estimation of both classes, which in turn can be used to evaluate the overall performance of a mixed traffic road.

Detector data can be used to construct cumulative flow curves, which in turn can be used to estimate the traffic state. However, this approach is subject to the cumulative error problem. Multiple studies propose to mitigate the cumulative error problem using probe trajectory data. These studies often assume “no overtaking” and thus that the cumulative flow is zero over probe trajectories. However, in multi-lane traffic this assumption is often violated. Therefore, we present an approach to estimate the change in cumulative flow along probe trajectories between detectors based on disaggregated detector data. The approach is tested with empirical data and in microsimulation. This shows that the approach is a clear improvement over assuming “no overtaking” in free-flow conditions. However, the benefits are not clear in varying traffic conditions. The approach can be applied in practice to mitigate the cumulative error problem and estimate the traffic state based on the resulting cumulative flow curves. As the performance of the approach depends on the changes in traffic conditions, it is suggested to use the probe speed observations between detectors to assign an uncertainty to the change in cumulative flow estimates. Furthermore, a potential option for future work is to use more elaborate schemes to estimate the probe relative flow between detectors, which may, for instance, combine probe speeds with estimates of the macroscopic states along the probe trajectory. If these macroscopic estimates are based on the cumulative flow curves at the detector locations, this would result in an iterative approach.

Lane drops are a common bottleneck source on motorway networks. Congestion sets in upstream of a lane drop as a result of the lane changing activity of merging vehicles. This causes the queue discharge rate at the bottleneck to decrease and drop below the capacity, leading to capacity drop and further congestion. The objective of this study is to minimize the total travel time of the system by controlling lateral flows upstream of the lane drop. This is equivalent to maximizing the exit flows at the bottleneck. An optimization problem is formulated for a 3–2 lane drop section with high inflow. The problem is solved for different test cases where the direction of lateral flows being controlled is varied. An incentive based macroscopic model representing the natural lane changing scenario is used as a benchmark for comparison. The results showed that by influencing the lateral flows upstream of the bottleneck, the queue discharge rate increased by more than 4.5%. The total travel time of the system was consequently found to be reduced. The improvements in performance were primarily a result of the distribution of lane changing activity over space and the balancing of flow among the lanes which lead to the decrease in the severity of congestion. The findings reveal a potentially effective way to reduce the severity of congestion upstream of lane drop bottlenecks during high demand which could be implemented using roadside and in-car advisory systems.