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Abstract Due to the wealth of exposome data from longitudinal cohort studies that is currently available, the need for methods to adequately analyze these data is growing. We propose an approach in which machine learning is used to identify longitudinal exposome-related predictors of health, and illustrate its potential through an application. Our application involves studying the relation between exposome and self-perceived health based on the 30-year running Doetinchem Cohort Study. Random Forest (RF) was used to identify the strongest predictors due to its favorable prediction performance in prior research. The relation between predictors and outcome was visualized with partial dependence and accumulated local effects plots. To facilitate interpretation, exposures were summarized by expressing them as the average exposure and average trend over time. The RF model’s ability to discriminate poor from good self-perceived health was acceptable (Area-Under-the-Curve = 0.707). Nine exposures from different exposome-related domains were largely responsible for the model’s performance, while 87 exposures seemed to contribute little to the performance. Our approach demonstrates that ML can be interpreted more than widely believed, and can be applied to identify important longitudinal predictors of health over the life course in studies with repeated measures of exposure. The approach is context-independent and broadly applicable.

BackgroundUrban renewal traditionally involves policy sectors such as housing, transport, and employment, which potentially can enhance the health of residents living in deprived areas. Additional involvement of the public health sector might increase the health impact of these urban renewal activities. This study evaluates the health impact of an additional focus on health, under the heading of Healthy District Experiments (HDE), within districts where an urban renewal programme was carried out.MethodsWe evaluated changes in health outcomes before the start of the HDE and after implementation, and compared these changes with health changes in control areas, e.g. districts from the urban renewal programme where no additional HDE was implemented. Additionally, we gathered information on the content of the experiments to determine what types of activities have been implemented.ResultsThe additional activities from the HDE were mostly aimed at strengthening the health care in the districts and at promoting physical activity. When we compared the prevalence in general health, mental health, overweight, obesity, smoking, and physical activity during the study period between the HDE districts and control districts, we found no significant differences in the rate of change. The study is limited by a small sample size and the cross-sectional nature of the data. These and other limitations are discussed.ConclusionWe found no evidence for a beneficial health impact of the activities that were initiated with a specific focus on health, within a Dutch urban renewal programme. Specific attention for network management and the integration of such activities in the wider programme, as well as an allocated budget might be needed in order to sort a health impact.

Dietary supplements are products that are widely used for instance as energisers or to lose weight. There have been cases reported where undeclared ingredients present in such supplements have caused adverse effects on the health of the user. As there are many different products to choose from, it seems impossible to predict which might contain harmful components and to ban them from the market. Nonetheless, the use of dietary supplements and the experiences of users are shared in online discussions. We describe the development of a search engine to retrieve products associated with certain effects. Upon application we were able to retrieve a list of dietary supplements that are repeatedly associated with excessive effects by users on public fora. The top of the list contains supplements that have previously been banned because they contained undeclared harmful components. The use of the search engine as described here is a powerful method for making a risk-based selection of dietary supplements which can then be analysed for the presence of illegal or other unwanted components.

Respondent-driven detection is a chain recruitment method used to sample contact persons of infected persons in order to enhance case finding. It starts with initial individuals, so-called seeds, who are invited for participation. Afterwards, seeds receive a fixed number of coupons to invite individuals with whom they had contact during a specific time period. Recruitees are then asked to do the same, resulting in successive waves of contact persons who are connected in one recruitment tree. However, often the majority of participants fail to invite others, or invitees do not accept an invitation, and recruitment stops after several waves. A mathematical model can help to analyse how various factors influence peer recruitment and to understand under which circumstances sustainable recruitment is possible. We implemented a stochastic simulation model, where parameters were suggested by empirical data from an online survey, to determine the thresholds for obtaining large recruitment trees and the number of waves needed to reach a steady state in the sample composition for individual characteristics. We also examined the relationship between mean and variance of the number of invitations sent out by participants and the probability of obtaining a large recruitment tree. Our main finding is that a situation where participants send out any number of coupons between one and the maximum number is more effective in reaching large recruitment trees, compared to a situation where the majority of participants does not send out any invitations and a smaller group sends out the maximum number of invitations. The presented model is a helpful tool that can assist public health professionals in preparing research and contact tracing using online respondent-driven detection. In particular, it can provide information on the required minimum number of successfully sent invitations to reach large recruitment trees, a certain sample composition or certain number of waves.

Activation of the β2 integrin lymphocyte function-associated antigen-1 (LFA-1) in T cells induces stabilization of proinflammatory AU-rich element (ARE)-bearing mRNAs, by triggering the nuclear-to-cytoplasmic translocation of the mRNA-binding and -stabilizing protein HuR. However, the mechanism by which LFA-1 engagement controls HuR localization is not known. Here, we identify and characterize four key regulators of LFA-1-induced changes in HuR activity: the p38 pathway kinase MK2 and the constitutive nuclear proteins hnRNPs C, H1 and K. LFA-1 engagement results in rapid, sequential activation of p38 and MK2. Post-LFA-1 activation, MK2 inducibly associates with both hnRNPC and HuR, resulting in the dissociation of HuR from hnRNPs C, H1 and K. Freed from the three hnRNPs, HuR translocates from the nucleus to the cytoplasm, and mediates the stabilization of labile cytokine transcripts. Our results suggest that the modulation of T cell cytokine mRNA half-life is an intricate process that is negatively regulated by hnRNPs C, H1 and K and requires MK2 as a critical activator.

Rapid growth of information technology development as well as increasing level of competition make every company need to establish an information system to support its business process. Research & Technology Transfer Directorate of Binus University is aware of this matter and makes a goal to improve the existing business process and develop a web-based information system that is able to support the existing business process to be more effective and efficient. This study aims to conduct an analysis and a design of information system for Research & Technology Transfer Directorate Binus University that can enhance the existing business process. Research used two methods, firstly data gathering done by conducting field studies and literature reviews, secondly the analysis and design of the system with object-oriented method. The result achieved from this research is a web-based information system that can support Research & Technology Transfer Directorate business process. The conclusion of this research is a new integrated web-based information system that can support and enhance current business process by connecting all parts of the system with the result to make all process more effective and efficient.

BACKGROUND:Large-scale regeneration programmes to improve the personal conditions and living circumstances in deprived areas may affect health and the lifestyle of the residents. Previous evaluations concluded that a large-scale urban regeneration programme in the Netherlands had some positive effects within 3.5 years. The aim of the current study was to evaluate the effects at the longer run. METHODS:With a quasi-experimental research design we assessed changes in the prevalence of general health, mental health, physical activity, overweight, obesity, and smoking between the pre-intervention (2003-04 -mid 2008) and intervention period (mid 2008-2013-14) in 40 deprived target districts and comparably deprived control districts. We used the Difference-in-Difference (DiD) to assess programme impact. Additionally, we stratified analyses by sex and by the intensity of the regeneration programme. RESULTS:Changes in health and health related behaviours from pre-intervention to the intervention period were about equally large in the target districts as in control districts. DiD impact estimates were inconsistent and not statistically significant. Sex differences in DiD estimates were not consistent or significant. Furthermore, DiD impact estimates were not consistently larger in target districts with more intensive intervention programmes. CONCLUSION:We found no evidence that this Dutch urban regeneration programme had an impact in the longer run on self-reported health and related behaviour at the area level.

In developing liposomes for in vivo use, it is important to design the liposomes to have optimal in vivo kinetics, and it is also necessary to identify optimal high-throughput production conditions for these liposomes. Previous work has not definitively established the general relationship between liposomes' configuration and composition, and their in vivo kinetics. Also, no straightforward method exists to calculate optimal liposome high-throughput production conditions for specific liposome compositions. This work presents first-principles quantitative correlations describing liposomes' in vivo drug leakage and vascular mass transfer kinetics. This work further presents a simple quantitative model relating specific liposome compositions to ideal high-throughput production parameters. The results have implications for the identification of promising liposome compositions via high-throughput screening methodologies, as well as the design and optimization of high-throughput reactors for liposome production.

Cancers often overexpress EGF and other growth factors to promote cell replication and migration. Previous work has not produced targeted drug carriers sensitive to abnormal amounts of growth factors. This work demonstrates that liposomes bearing EGF receptors covalently crosslinked to p-toluic acid or methyl-PEO(4)-NHS ester (or, in short, MRBLs) exhibit an increased rate of release of encapsulated drug compounds when EGF is present in solution. Furthermore, the modified EGF receptors retain the abilities to form dimers in the presence of EGF and bind specifically to EGF. These results demonstrate that MRBLs are sensitive to EGF in solution and indicate that MRBL-reconstituted modified EGF receptors, in the presence of EGF in solution, form dimers which increase MRBL permeability to encapsulated compounds.