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Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) implicates enhanced intrathecal chemotherapy, which is related to CNS toxicity. Whether CNS involvement alone contributes to CNS toxicity remains unclear. We studied the occurrence of all CNS toxicities, seizures, and posterior reversible encephalopathy syndrome (PRES) in children with ALL without enhanced intrathecal chemotherapy with CNS involvement (n = 64) or without CNS involvement (n = 256) by flow cytometry. CNS involvement increased the risk for all CNS toxicities, seizures, and PRES in univariate analysis and, after adjusting for induction therapy, for seizures (hazard ratio [HR] = 3.33; 95% confidence interval [CI]: 1.26–8.82; p = 0.016) and PRES (HR = 4.85; 95% CI: 1.71–13.75; p = 0.003).

Walking and cycling promotes physical activity and mental health. In many European cities, walking and cycling has increased and is a key part of transport planning. However, many cyclists and pedestrians still perceive themselves as neglected road users, face air pollutants, noise and fear travel injuries. Children are in particular vulnerable. The aim of this study is to present mobile interview methods (“go-/ride-alongs”) for promoting safe and healthy cycling/walking in urban transport planning. We present two studies from Berlin (a) and Leipzig (b), Germany. We conducted go-/ride-alongs with cyclists and pedestrians on (a) their commute home from work and (b) children on their way to school. We accompanied them and investigated how they experience commuting, the environment and discover ad-hoc situative behavior. We discuss our findings and transfer our knowledge gained through the mobile method into transport planning strategies. Safety is most often mentioned by all interviewees. Our studies show a high importance of in-situ/ad-hoc experiences for travel behavior, which can be examined with an interviewer accompanying. Our methods encourage interviewees to describe past experiences, how they shape their behavior or factors supporting/hindering active travel. We consider mobile methods important for exploring mobility and successful when complemented by participatory methods and instruments (e.g., participatory mapping, smartphone-apps, group walks). Therefore, the voice of vulnerable road users can be strengthened. In a next step individual local experiences and community knowledge could be incorporated in urban transport planning to improve active travel.

When commuters move around the city they are exposed to different environmental stressors, of which air and noise pollution have an especially adverse physical and mental health impact. Most exposure research uses sensor data (stationary or wearable) or closed questionnaires to measure personal exposure. However, these methods do not give insight into on-site perceptions of exposed individuals and their related behaviour. To address this, we discuss (1) existing methods to research perceived and measured exposure in transit and (2) introduce a novel mixed-method approach, which we tested in a case study in Chennai, India. We used Walking Interviews and GPS-tracking to investigate perceptions and behaviour regarding air and noise pollution on the move and combined it with data of wearable sensors. The results show that the perception of air and noise pollution is highly context-dependent. This mixed-method approach is advantageous for an investigation of perceived and objective exposure and the related behavioural patterns while moving around the city. Such qualitative and quantitative exposure data of commuters can be spatially visualized and communicated to decision-makers with help of qualitative geographic information system (GIS) approaches. We argue that the potential of this mixed-methods approach to support healthier daily commutes in urban areas should be further elaborated in urban and transport-related studies.

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Background: The exposure to air pollution and noise is severely impacting people & rsquo;s health and is especially high alongside urban road- and rail-traffic. In traditional exposure research, air pollution and noise are monitored with stationary measurement devices or based on models. During the last years, mobile measurement techniques with GPS-tracking have increased. Moreover, studies have investigated another dimension of personal exposure: the perceived exposure. Aim: Most of these studies make use of quantitative methods such as surveys, complemented by stationary or wearable sensors. Little research exist that applies qualitative methods to examine how people experience and perceive exposure on-the-move, contrasting it to actual measurements. The aim of this paper is to discuss the potential of a novel method, which extends the dimensions of personal exposure by including the situational context of exposure perception. Methods/case study: Firstly, different methods for exposure research are presented. Secondly, we introduce a novel mixed-method approach, exploring cyclists and pedestrians perceived and measured exposure on-the-move by combining mobile interviews (Go-/Ride-Alongs) and wearable sensors. We will present the methodological findings using a case study and have a quantitative method (smartphone questionnaire, wearable sensors) as a reference. Results and discussion: The differences of perceived and measured exposure, proven through the reference method, are a result of different situational contexts as shown by the mobile interviews (knowledge, embodied experience, life situation, activities). The methodological findings show, that mobile methods complemented by wearables introduce new dimensions of personal exposure: they shed light on the situational contexts that affect exposure perception during commute. Conclusion: We argue that both, perceived and measured exposure to air pollution and noise, need to be considered simultaneously. C

Global population growth, urbanization, and climate change worsen the immediate environment of many individuals. Elevated concentrations of air pollutants, higher levels of acoustic noise, and more heat days, as well as increasingly complex mixtures of pollutants pose health risks for urban inhabitants. There is a growing awareness of the need to record personal environmental conditions (“the human exposome”) and to study options and implications of adaptive and protective behavior of individuals. The vast progress in smart technologies created wearable sensors that record environmental as well as spatio-temporal data while accompanying a person. Wearable sensing has two aspects: firstly, the exposure of an individual is recorded, and secondly, individuals act as explorers of the urban area. A literature review was undertaken using scientific literature databases with the objective to illustrate the state-of-the-art of person-based environmental sensing in urban settings. We give an overview of the study designs, highlight and compare limitations as well as results, and present the results of a keyword analysis. We identify current trends in the field, suggest possible future advancements, and lay out take-home messages for the readers. There is a trend towards studies that involve various environmental parameters and it is becoming increasingly important to identify and quantify the influence of various conditions (e.g., weather, urban structure, travel mode) on people’s exposure.

Feedback on personal exposure to air pollution, noise or extreme temperatures through wearable sensors or sensors installed at home or in the workplace can offer information that might motivate behaviours to mitigate exposure. As personal measurement devices are becoming increasingly accessible, it is important to evaluate the effects of such sensors on human perception and behaviour. We conducted a systematic literature research and identified 33 studies, analysing the effects of personal feedback on air pollution, noise and temperatures. Feedback was given through reports including different forms of visualization, in-person or over the telephone, or directly on the sensor or through a phone app. The exposure feedback led to behaviour changes particularly for noise and temperature feedback while findings on behaviour adaptation to avoid air pollution were mixed. Most studies reported increased awareness and knowledge from receiving exposure feedback. Many participants in studies on air pollution reported low levels of self-efficacy regarding exposure mitigation. For a better understanding of the effects of personal exposure feedback, more studies are required, particularly providing feedback from wearable sensors measuring outdoor air pollution, noise and temperature.

PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR. An informative FCM-marker was found in 96.2% and only two patients (0.14%) had non-informative FCM and non-informative PCR-markers. The overall 5-year event-free survival was 86.1% with a cumulative incidence of relapse (CIR5y) of 9.5%. FCM-MRD levels on days 15 (HzR 4.0, p < 0.0001), 29 (HzR 2.7, p < 0.0001), and 79 (HzR 3.5, p < 0.0001) associated with hazard of relapse adjusted for age, cytogenetics, and WBC. The early (day 15) response associated with CIR5y adjusted for day 29 FCM-MRD, with higher levels in adults (median 2.4 × 10-2 versus 5.2 × 10-3, p < 0.0001). Undetectable FCM- and/or PCR-MRD on day 29 identified patients with a very good outcome (CIR5y = 3.2%). For patients who did not undergo transplantation, day 79 FCM-MRD > 10-4 associated with a CIR5y = 22.1%. In conclusion, FCM-MRD performed in a multicenter setting is a clinically useful method for MRD-based treatment stratification in BCP-ALL.

PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR. An informative FCM-marker was found in 96.2% and only two patients (0.14%) had non-informative FCM and non-informative PCR-markers. The overall 5-year event-free survival was 86.1% with a cumulative incidence of relapse (CIR5y) of 9.5%. FCM-MRD levels on days 15 (HzR 4.0, p < 0.0001), 29 (HzR 2.7, p < 0.0001), and 79 (HzR 3.5, p < 0.0001) associated with hazard of relapse adjusted for age, cytogenetics, and WBC. The early (day 15) response associated with CIR5y adjusted for day 29 FCM-MRD, with higher levels in adults (median 2.4 x 10(-2) versus 5.2 x 10(-3), p < 0.0001). Undetectable FCM- and/or PCR-MRD on day 29 identified patients with a very good outcome (CIR5y = 3.2%). For patients who did not undergo transplantation, day 79 FCM-MRD > 10(-4) associated with a CIR5y = 22.1%. In conclusion, FCM-MRD performed in a multicenter setting is a clinically useful method for MRD-based treatment stratification in BCP-ALL.

Minimal residual disease (MRD) measured by PCR of clonal IgH/TCR rearrangements predicts relapse in T-cell acute lymphoblastic leukemia (T-ALL) and serves as risk stratification tool. Since 10% of patients have no suitable PCR-marker, we evaluated flowcytometry (FCM)-based MRD for risk stratification. We included 274 T-ALL patients treated in the NOPHO-ALL2008 protocol. MRD was measured by six-color FCM and real-time quantitative PCR. Day 29 PCR-MRD (cut-off 10-3) was used for risk stratification. At diagnosis, 93% had an FCM-marker for MRD monitoring, 84% a PCR-marker, and 99.3% (272/274) had a marker when combining the two. Adjusted for age and WBC, the hazard ratio for relapse was 3.55 (95% CI 1.4-9.0, p = 0.008) for day 29 FCM-MRD ≥ 10-3 and 5.6 (95% CI 2.0-16, p = 0.001) for PCR-MRD ≥ 10-3 compared with MRD < 10-3. Patients stratified to intermediate-risk therapy on day 29 with MRD 10-4-<10-3 had a 5-year event-free survival similar to intermediate-risk patients with MRD < 10-4 or undetectable, regardless of method for monitoring. Patients with day 15 FCM-MRD < 10-4 had a cumulative incidence of relapse of 2.3% (95% CI 0-6.8, n = 59). Thus, FCM-MRD allows early identification of patients eligible for reduced intensity therapy, but this needs further studies. In conclusion, FCM-MRD provides reliable risk prediction for T-ALL and can be used for stratification when no PCR-marker is available.

IntroductionTraffic jams, congestion and pollution demand sustainable modes of transport. To increase the appeal of cycling, bicycle-users' perceptions and needs should be acknowledged by decision-makers. However, traditional transport planning mainly focuses on quantitative, infrastructural data. To address this gap, this study explores to what extent decision-makers are aware of cyclists' needs and perceptions. Furthermore, the study compares the assessments about cycling of decision-makers and cyclists in the city of Leipzig, Germany.MethodsQualitative Interviews with 13 cyclists and similarly structured interviews with 6 experts from politics and planning were compared using qualitative content analysis. Two main topics were examined: (1) the reasons for cycling and (2) the perceived environment (built, natural and individually perceived). To integrate the spatial context, the interviewees draw sketch maps which were analyzed and compared using geo-information systems.ResultsExperts assume that main roads with cycling infrastructure are decisive for fast and safe cycling and cyclists agree with this statement. However, cyclists further refer to the positive effects of green spaces, the experience of the natural environment (e.g. fresh air) as well as the healthy and recreational effect of cycling. Cyclists prefer taking side roads and are prepared to use detours to integrate the natural environment and avoid traffic jams, noise and air pollution – these aspects were rarely acknowledged by decision-makers.DiscussionWe conclude that urban planners need to involve cyclists' perceptions more explicitly. Integrating cyclists' experiences in planning processes using sketch maps and interviews are beneficial, complementing quantitative approaches to enhance the understanding of cyclist behavior. The findings are essential to stress the importance of participatory approaches in urban planning to promote a sustainable, healthy and environmentally friendly urban developme

Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (A), 266 were 10-17 years (B) and 221 were 18-45 years (C). Sixteen patients (three adults) died during induction. All others achieved remission after induction or 1-3 intensive blocks. Subsequently, 45 patients (12 adults) died, 122 patients relapsed (32 adults) with a median time to relapse of 1.6 years and 13 (no adult) developed a second malignancy. Median follow-up time was 4.6 years. Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, P<0.001), KMT2A rearrangements (6%/5%/3%, P<0.001) and higher day 29 residual leukemia for B-lineage (P<0.001), but not T-ALL (P = 0.53). Event-free survival rates (pEFS(5y)) were 89 +/- 1% (A), 80 +/- 3% (B) and 74 +/- 4% (C) with significant differences only for non-high risk groups. Except for thrombosis, pancreatitis and osteonecrosis, the risk of 19 specified toxicities was not enhanced by age above 10 years. In conclusion, a pediatric-based protocol is tolerable and effective for young adults, despite their increased frequency of higher risk features.

The ECETOC TRA model (presently version 3.1) is often used to estimate worker inhalation and dermal exposure in regulatory risk assessment. The dermal model in ECETOC TRA has not yet been validated by comparison with independent measured exposure levels. This was the goal of the present study. Measured exposure levels and relevant contextual information were gathered via literature search, websites of relevant occupational health institutes and direct requests for data to industry. Exposure data were clustered in so-called exposure cases, which are sets of data from one data source that are expected to have the same values for input parameters in the ECETOC TRA dermal exposure model. For each exposure case, the 75th percentile of measured values was calculated, because the model intends to estimate these values. The input values for the parameters in ECETOC TRA were assigned by an expert elicitation and consensus building process, based on descriptions of relevant contextual information. From more than 35 data sources, 106 useful exposure cases were derived, that were used for direct comparison with the model estimates. The exposure cases covered a large part of the ECETOC TRA dermal exposure model. The model explained 37% of the variance in the 75th percentiles of measured values. In around 80% of the exposure cases, the model estimate was higher than the 75th percentile of measured values. In the remaining exposure cases, the model estimate may not be sufficiently conservative. The model was shown to have a clear bias towards (severe) overestimation of dermal exposure at low measured exposure values, while all cases of apparent underestimation by the ECETOC TRA dermal exposure model occurred at high measured exposure values. This can be partly explained by a built-in bias in the effect of concentration of substance in product used, duration of exposure and the use of protective gloves in the model. The effect of protective gloves was calculated to be on average a

RIVM rapport:Het veiligheidsinformatieblad (VIB) is het belangrijkste instrument voor het verstrekken van informatie over veilig gebruik van stoffen en chemische mengsels aan professionele en industriële gebruikers. De REACH-wetgeving is de huidige wettelijke basis voor de VIBs in Europa. Voor geregistreerde stoffen in hoeveelheden van 10 ton of meer per jaar per registrant, moeten registranten ook blootstellingsscenario's (aangeduid als "ES", de afkorting voor "Exposure Scenario") opstellen en deze toevoegen als bijlage aan de VIB's. ES worden vereist voor stoffen die voldoen aan de criteria van een van de gevarenklassen van artikel 14 (4) van REACH of stoffen die als PBT of vPvB zijn aangemerkte en voor alle in de registratie voorziene gebruiken die tot blootstelling kunnen leiden. In de ES worden voor alle geïdentificeerde gebruiken de relevante operationele omstandigheden (OC) en risicobeheersmaatregelen (RMM) omschreven die nodig zijn voor een veilig gebruik. Een dergelijke verplichting voor een ES geldt niet voor mengsels van chemische stoffen. Echter, de informatie uit de blootstellingsscenario's van de stoffen waaruit het mengsel bestaat, moet wél in een bepaalde vorm worden gepresenteerd in het VIB van het mengsel. Met '(e)SDS' worden in dit rapport alle VIBs aangeduid met en zonder ES. Om diverse signalen uit de praktijk van onvoldoende kwaliteit te verifiëren, en omdat (e)SDS als een primaire bron van informatie voor werkgevers worden beschouwd bij het nakomen van hun arbo-verplichtingen, heeft de Nederlandse Inspectie-SZW (I-SZW) een systematische evaluatie laten uitvoeren van een 50- tal (e)SDS die door de I-SZW inspecteurs zijn verzameld tijdens een REACH inspectieproject in 2012. Het gaat hier om (e)SDS die bepaalde tekortkomingen tonen volgens een snelle scan van de inspecteurs zelf. Het doel is om meer inzicht te krijgen in de stand van zaken rond te kwaliteit van de (e)SDS. De evaluatie is uitgevoerd door TNO Triskelion BV onder begeleiding door Bureau REACH en, The safety data sheet (SDS) is the main instrument for providing information on the safe use of chemical substances and mixtures to professional and industrial users. The REACH legislation is the current legal basis for the SDS in Europe. For registered substances in quantities of 10 tons or more per year per registrant, registrants should also describe the various relevant exposure scenarios ("ES"), and annex them to the SDS. ES are required for all identified uses that can lead to exposure. ES are further required for substances that meet the criteria of article 14 (4) of REACH or are identified as PBT or vPvB. For each ES relevant operational conditions (OC) and risk management measures (RMM) need to be described that are necessary for safe use. Such a requirement does not apply to mixtures of chemicals. However, the information from the exposure scenarios of the substances in the mixture must be somehow incorporated in the SDS of the mixture. The abbreviation "(e)SDS" in this report is used for all types of SDSs with or without exposure scenarios. To verify various field signals of poor quality and because employers use the (e)SDS as a primary source of information to meet their OSH-obligations, the Dutch Labor Inspectorate (I-SZW) commissioned a systematic review of 50 (e)SDS collected during a REACH enforcement project from 2012. These are (e)SDS that the inspectors, based on a quick scan, identified as showing certain shortcomings. The study was conducted by TNO Triskelion BV under the supervision of Bureau REACH and is intended as input into the discussion on possible further actions to improve the quality and usefulness of the (e )SDS. The results for the studied (e) SDS are summarized as follows. For nearly half of the concerned (e)SDS there were strong indications that they were not up to date. The problems identified were related to the use of the Dutch language and incomplete or no specifications on skin protection. In some (e)SDS that reported incompat