Motives of contributing personal data for health research:(non-)participation in a Dutch biobank

BACKGROUND: Large-scale, centralized data repositories are playing a critical and unprecedented role in fostering innovative health research, leading to new opportunities as well as dilemmas for the medical sciences. Uncovering the reasons as to why citizens do or do not contribute to such repositories, for example, to population-based biobanks, is therefore crucial. We investigated and compared the views of existing participants and non-participants on contributing to large-scale, centralized health research data repositories with those of ex-participants regarding the decision to end their participation. This comparison could yield new insights into motives of participation and non-participation, in particular the behavioural change of withdrawal. METHODS: We conducted 36 in-depth interviews with ex-participants, participants, and non-participants of a three-generation, population-based biobank in the Netherlands. The interviews focused on the respondents' decision-making processes relating to their participation in a large-scale, centralized repository for health research data. RESULTS: The decision of participants and non-participants to contribute to the biobank was motivated by a desire to help others. Whereas participants perceived only benefits relating to their participation and were unconcerned about potential risks, non-participants and ex-participants raised concerns about the threat of large-scale, centralized public data repositories and public institutes, such as social exclusion or commercialization. Our analysis of ex-participants' perceptions suggests that intrapersonal characteristics, such as levels of trust in society, participation conceived as a social norm, and basic societal values account for differences between participants and non-participants. CONCLUSIONS: Our findings indicate the fluidity of motives centring on helping others in decisions to participate in large-scale, centralized health research data repositories. Efforts to improve participation should focus on enhancing the trustworthiness of such data repositories and developing layered strategies for communication with participants and with the public. Accordingly, personalized approaches for recruiting participants and transmitting information along with appropriate regulatory frameworks are required, which have important implications for current data management and informed consent procedures

Filtering Deterministic Layer Effects in Imaging

Sensor array imaging arises in applications such as nondestructive evaluation of materials with ultrasonic waves, seismic exploration, and radar. The sensors probe a medium with signals and record the resulting echoes, which are then processed to determine the location and reflectivity of remote reflectors. These could be defects in materials such as voids, fault lines or salt bodies in the earth, and cars, buildings, or aircraft in radar applications. Imaging is relatively well understood when the medium through which the signals propagate is smooth, and therefore nonscattering. But in many problems the medium is heterogeneous, with numerous small inhomogeneities that scatter the waves. We refer to the collection of inhomogeneities as clutter, which introduces an uncertainty in imaging because it is unknown and impossible to estimate in detail. We model the clutter as a random process. The array data is measured in one realization of the random medium, and the challenge is to mitigate cumulative clutter scattering so as to obtain robust images that are statistically stable with respect to different realizations of the inhomogeneities. Scatterers that are not buried too deep in clutter can be imaged reliably with the coherent interferometric (CINT) approach. But in heavy clutter the signal-to-noise ratio (SNR) is low and CINT alone does not work. The “signal,” the echoes from the scatterers to be imaged, is overwhelmed by the “noise,” the strong clutter reverberations. There are two existing approaches for imaging at low SNR: The first operates under the premise that data are incoherent so that only the intensity of the scattered field can be used. The unknown coherent scatterers that we want to image are modeled as changes in the coefficients of diffusion or radiative transport equations satisfied by the intensities, and the problem becomes one of parameter estimation. Because the estimation is severely ill-posed, the results have poor resolution, unless very good prior information is available and large arrays are used. The second approach recognizes that if there is some residual coherence in the data, that is, some reliable phase information is available, it is worth trying to extract it and use it with well-posed coherent imaging methods to obtain images with better resolution. This paper takes the latter approach and presents a first attempt at enhancing the SNR of the array data by suppressing medium reverberations. It introduces filters, or annihilators of layer backscatter, that are designed to remove primary echoes from strong, isolated layers in a medium with additional random layering at small, subwavelength scales. These strong layers are called deterministic because they can be imaged from the data. However, our goal is not to image the layers, but to suppress them and thus enhance the echoes from compact scatterers buried deep in the medium. Surprisingly, the layer annihilators work better than intended, in the sense that they suppress not only the echoes from the deterministic layers, but also multiply scattered ones in the randomly layered structure. Following the layer annihilators presented here, other filters of general, nonlayered heavy clutter have been developed. We review these more recent developments and the challenges of imaging in heavy clutter in the introduction in order to place the research presented here in context. We then present in detail the layer annihilators and show with analysis and numerical simulations how they work

Therapies with CCL25 require controlled release via microparticles to avoid strong inflammatory reactions

Background: Chemokine therapy with C-C motif chemokine ligand 25 (CCL25) is currently under investigation as a promising approach to treat articular cartilage degeneration. We developed a delayed release mechanism based on Poly (lactic-co-glycolic acid) (PLGA) microparticle encapsulation for intraarticular injections to ensure prolonged release of therapeutic dosages. However, CCL25 plays an important role in immune cell regulation and inflammatory processes like T-cell homing and chronic tissue inflammation. Therefore, the potential of CCL25 to activate immune cells must be assessed more thoroughly before further translation into clinical practice. The aim of this study was to evaluate the reaction of different immune cell subsets upon stimulation with different dosages of CCL25 in comparison to CCL25 released from PLGA particles. Results: Immune cell subsets were treated for up to 5 days with CCL25 and subsequently analyzed regarding their cytokine secretion, surface marker expression, polarization, and migratory behavior. The CCL25 receptor C-C chemokine receptor type 9 (CCR9) was expressed to a different extent on all immune cell subsets. Direct stimulation of peripheral blood mononuclear cells (PBMCs) with high dosages of CCL25 resulted in strong increases in the secretion of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta), tumor-necrosis-factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), upregulation of human leukocyte antigen-DR (HLA-DR) on monocytes and CD4(+) T-cells, as well as immune cell migration along a CCL25 gradient. Immune cell stimulation with the supernatants from CCL25 loaded PLGA microparticles caused moderate increases in MCP-1, IL-8, and IL-1 beta levels, but no changes in surface marker expression or migration. Both CCL25-loaded and unloaded PLGA microparticles induced an increase in IL-8 and MCP-1 release in PBMCs and macrophages, and a slight shift of the surface marker profile towards the direction of M2-macrophage polarization. Conclusions: While supernatants of CCL25 loaded PLGA microparticles did not provoke strong inflammatory reactions, direct stimulation with CCL25 shows the critical potential to induce global inflammatory activation of human leukocytes at certain concentrations. These findings underline the importance of a safe and reliable release system in a therapeutic setup. Failure of the delivery system could result in strong local and systemic inflammatory reactions that could potentially negate the benefits of chemokine therapy

Fourier Method for Approximating Eigenvalues of Indefinite Stekloff Operator

We introduce an efficient method for computing the Stekloff eigenvalues associated with the Helmholtz equation. In general, this eigenvalue problem requires solving the Helmholtz equation with Dirichlet and/or Neumann boundary condition repeatedly. We propose solving the related constant coefficient Helmholtz equation with Fast Fourier Transform (FFT) based on carefully designed extensions and restrictions of the equation. The proposed Fourier method, combined with proper eigensolver, results in an efficient and clear approach for computing the Stekloff eigenvalues.Comment: 12 pages, 4 figure

Thermally activated reorientation of di-interstitial defects in silicon

We propose a di-interstitial model for the P6 center commonly observed in ion implanted silicon. The di-interstitial structure and transition paths between different defect orientations can explain the thermally activated transition of the P6 center from low-temperature C1h to room-temperature D2d symmetry. The activation energy for the defect reorientation determined by ab initio calculations is 0.5 eV in agreement with the experiment. Our di-interstitial model establishes a link between point defects and extended defects, di-interstitials providing the nuclei for the growth.Comment: 12 pages, REVTeX, Four figures, submitted to Phys. Rev. Let

(Un)Healthy in the City:Respiratory, Cardiometabolic and Mental Health Associated with Urbanity

Research has shown that health differences exist between urban and rural areas. Most studies conducted, however, have focused on single health outcomes and have not assessed to what extent the association of urbanity with health is explained by population composition or socioeconomic status of the area. Our aim is to investigate associations of urbanity with four different health outcomes (i.e. lung function, metabolic syndrome, depression and anxiety) and to assess whether these associations are independent of residents' characteristics and area socioeconomic status.Our study population consisted of 74,733 individuals (42% males, mean age 43.8) who were part of the baseline sample of the LifeLines Cohort Study. Health outcomes were objectively measured with spirometry, a physical examination, laboratory blood analyses, and a psychiatric interview. Using multilevel linear and logistic regression models, associations of urbanity with lung function, and prevalence of metabolic syndrome, major depressive disorder and generalized anxiety disorder were assessed. All models were sequentially adjusted for age, sex, highest education, household equivalent income, smoking, physical activity, and mean neighborhood income.As compared with individuals living in rural areas, those in semi-urban or urban areas had a poorer lung function (β -1.62, 95% CI -2.07;-1.16), and higher prevalence of major depressive disorder (OR 1.65, 95% CI 1.35;2.00), and generalized anxiety disorder (OR 1.58, 95% CI 1.35;1.84). Prevalence of metabolic syndrome, however, was lower in urban areas (OR 0.51, 95% CI 0.44;0.59). These associations were only partly explained by differences in residents' demographic, socioeconomic and lifestyle characteristics and socioeconomic status of the areas.Our results suggest a differential health impact of urbanity according to type of disease. Living in an urban environment appears to be beneficial for cardiometabolic health but to have a detrimental impact on respiratory function and mental health. Future research should investigate which underlying mechanisms explain the differential health impact of urbanity