Development of an international survey attitude scale: measurement equivalence, reliability, and predictive validity

Declining response rates worldwide have stimulated interest in understanding what may be influencing this decline and how it varies across countries and survey populations. In this paper, we describe the development and validation of a short 9-item survey attitude scale that measures three important constructs, thought by many scholars to be related to decisions to participate in surveys, that is, survey enjoyment, survey value, and survey burden. The survey attitude scale is based on a literature review of earlier work by multiple authors. Our overarching goal with this study is to develop and validate a concise and effective measure of how individuals feel about responding to surveys that can be implemented in surveys and panels to understand the willingness to participate in surveys and improve survey effectiveness. The research questions relate to factor structure, measurement equivalence, reliability, and predictive validity of the survey attitude scale. The data came from three probability-based panels: the German GESIS and PPSM panels and the Dutch LISS panel. The survey attitude scale proved to have a replicable three-dimensional factor structure (survey enjoyment, survey value, and survey burden). Partial scalar measurement equivalence was established across three panels that employed two languages (German and Dutch) and three measurement modes (web, telephone, and paper mail). For all three dimensions of the survey attitude scale, the reliability of the corresponding subscales (enjoyment, value, and burden) was satisfactory. Furthermore, the scales correlated with survey response in the expected directions, indicating predictive validity

How to survey displaced workers in Switzerland ? Sources of bias and ways around them

Studying career outcomes after job loss is challenging because individually displaced worker form a self-selected group. Indeed, the same factors causing the workers to lose their jobs, such as lack of motivation, may also reduce their re-employment prospects. Using data from plant closures where all workers were displaced irrespective of their individual characteristics offers a way around this selection bias. There is no systematic data collection on workers displaced by plant closure in Switzerland. Accordingly, we conducted our own survey on 1200 manufacturing workers who had lost their job 2 years earlier. The analysis of observational data gives rise to a set of methodological challenges, in particular nonresponse bias. Our survey addressed this issue by mixing data collection modes and repeating contact attempts. In addition, we combined the survey data with data from the public unemployment register to examine the extent of nonresponse bias. Our analysis suggests that some of our adjustments helped to reduce bias. Repeated contact attempts increased the response rate, but did not reduce nonresponse bias. In contrast, using telephone interviews in addition to paper questionnaires helped to substantially improve the participation of typically underrepresented subgroups. However, the survey respondents still differ from nonrespondents in terms of age, education and occupation. Interestingly, these differences have no significant impact on the substantial conclusion about displaced workers' re-employment prospects

Effective Melanoma Immunotherapy in Mice by the Skin-Depigmenting Agent Monobenzone and the Adjuvants Imiquimod and CpG

Background: Presently melanoma still lacks adequate treatment options for metastatic disease. While melanoma is exceptionally challenging to standard regimens, it is suited for treatment with immunotherapy based on its immunogenicity. Since treatment-related skin depigmentation is considered a favourable prognostic sign during melanoma intervention, we here aimed at the reverse approach of directly inducing vitiligo as a shortcut to effective anti-melanoma immunity. Methodology and Principal Findings: We developed an effective and simple to use form of immunotherapy by combining the topical skin-bleaching agent monobenzone with immune-stimulatory imiquimod cream and cytosine-guanine oligodeoxynucleotides (CpG) injections (MIC therapy). This powerful new approach promptly induced a melanoma antigen-specific immune response, which abolished subcutaneous B16. F10 melanoma growth in up to 85% of C57BL/6 mice. Importantly, this regimen induced over 100 days of tumor-free survival in up to 60% of the mice, and forcefully suppressed tumor growth upon re-challenge either 65- or 165 days after MIC treatment cessation. Conclusions: MIC therapy is effective in eradicating melanoma, by vigilantly incorporating NK-, B-and T cells in its therapeutic effect. Based on these results, the MIC regimen presents a high-yield, low-cost and simple therapy, readily applicable in the clini

Measuring serotonin synthesis: from conventional methods to PET tracers and their (pre)clinical implications

The serotonergic system of the brain is complex, with an extensive innervation pattern covering all brain regions and endowed with at least 15 different receptors (each with their particular distribution patterns), specific reuptake mechanisms and synthetic processes. Many aspects of the functioning of the serotonergic system are still unclear, partially because of the difficulty of measuring physiological processes in the living brain. In this review we give an overview of the conventional methods of measuring serotonin synthesis and methods using positron emission tomography (PET) tracers, more specifically with respect to serotonergic function in affective disorders. Conventional methods are invasive and do not directly measure synthesis rates. Although they may give insight into turnover rates, a more direct measurement may be preferred. PET is a noninvasive technique which can trace metabolic processes, like serotonin synthesis. Tracers developed for this purpose are α-[11C]methyltryptophan ([11C]AMT) and 5-hydroxy-L-[β-11C]tryptophan ([11C]5-HTP). Both tracers have advantages and disadvantages. [11C]AMT can enter the kynurenine pathway under inflammatory conditions (and thus provide a false signal), but this tracer has been used in many studies leading to novel insights regarding antidepressant action. [11C]5-HTP is difficult to produce, but trapping of this compound may better represent serotonin synthesis. AMT and 5-HTP kinetics are differently affected by tryptophan depletion and changes of mood. This may indicate that both tracers are associated with different enzymatic processes. In conclusion, PET with radiolabelled substrates for the serotonergic pathway is the only direct way to detect changes of serotonin synthesis in the living brain

Acute exercise leads to regulation of Telomere-Associated genes and MicroRNA expression in immune Cells

Telomeres are specialized nucleoprotein structures that protect chromosomal ends from degradation. These structures progressively shorten during cellular division and can signal replicative senescence below a critical length. Telomere length is predominantly maintained by the enzyme telomerase. Significant decreases in telomere length and telomerase activity are associated with a host of chronic diseases; conversely their maintenance underpins the optimal function of the adaptive immune system. Habitual physical activity is associated with longer leukocyte telomere length; however, the precise mechanisms are unclear. Potential hypotheses include regulation of telomeric gene transcription and/or microRNAs (miRNAs). We investigated the acute exercise-induced response of telomeric genes and miRNAs in twenty-two healthy males (mean age = 24.1±1.55 years). Participants undertook 30 minutes of treadmill running at 80% of peak oxygen uptake. Blood samples were taken before exercise, immediately post-exercise and 60 minutes post-exercise. Total RNA from white blood cells was submitted to miRNA arrays and telomere extension mRNA array. Results were individually validated in white blood cells and sorted T cell lymphocyte subsets using quantitative real-time PCR (qPCR). Telomerase reverse transcriptase (TERT) mRNA (P = 0.001) and sirtuin-6 (SIRT6) (P<0.05) mRNA expression were upregulated in white blood cells after exercise. Fifty-six miRNAs were also differentially regulated post-exercise (FDR <0.05). In silico analysis identified four miRNAs (miR-186, miR-181, miR-15a and miR-96) that potentially targeted telomeric gene mRNA. The four miRNAs exhibited significant upregulation 60 minutes post-exercise (P<0.001). Telomeric repeat binding factor 2, interacting protein (TERF2IP) was identified as a potential binding target for miR-186 and miR-96 and demonstrated concomitant downregulation (P<0.01) at the corresponding time point. Intense cardiorespiratory exercise was sufficient to differentially regulate key telomeric genes and miRNAs in white blood cells. These results may provide a mechanistic insight into telomere homeostasis and improved immune function and physical health. Funding NHMR

Trapped electrons in the quantum degenerate regime

A full strength Coulomb interaction between trapped electrons can be felt only in absence of a neutralizing background. In order to study quantum degenerate electrons without such a background, an external trap is needed to compensate for the strong electronic repulsion. As a basic model for such a system, we study a trapped electron pair in a harmonic trap with an explicit inclusion of its Coulomb interaction. We find the eigenenergy of the ground state, confirming earlier work in the context of harmonium. We extend this to a complete set of properly scaled energies for any value of the trapping strength, including the excited states. The problem is solved either numerically or by making harmonic approximations to the potential. As function of the trapping strength a crossover can be made from the strongly to the weakly-coupled regime, and we show that in both regimes perturbative methods based on a pair-wise electron description would be effective for a many-particle trapped electron system, which resembles a Wigner crystal in the ground state of the strongly coupled limit

Chimeric bispecific OC/TR monoclonal antibody mediates lysis of tumor cells expressing the folate-binding protein (MOv18) and displays decreased immunogenicity in patients

The bispecific OC/TR monoclonal antibody (mAb) cross-links the CD3 molecule on T cells with the human folate-binding protein (FBP), which is highly expressed on nonmucinous ovarian carcinomas. Clinical trials of patients with ovarian carcinoma with the OC/TR mAb have shown some complete and partial responses. Most patients developed human anti-murine immunoglobulin antibodies (HAMA), which can inhibit OC/TR mAb-mediated lysis. We generated a chimeric version of the OC/TR mAb to decrease the immunogenicity of the OC/TR mAb and to allow more extended treatment schedules. Sp2/0 myeloma cells were transfected with chimeric heavy- and light-chain genes encoding the anti-CD3 mAb and the MOv18 mAb, respectively, which are reactive with FBP. The resulting cell line produced 80 micrograms/ml of total immunoglobulin G (IgG), of which 11.5% was the functionally active chimeric OC/TR mAb. Chimeric OC/TR F(ab')2 fragments mediated lysis of IGROV-1 ovarian carcinoma cells by human T cells at antibody concentrations of > or = 1 pg/ml. Specific lysis was still detectable at an effector-to-target cell ratio as low as 0.4. Two patients with ovarian carcinoma treated with F(ab')2 fragments of the murine OC/TR developed distinct HAMA titers, which were mainly anti-idiotypic and only partly directed against the murine antibody constant regions. However, of the two patients that were treated with the F(ab')2 fragments of the chimeric OC/TR mAb, only one developed a low transient HAMA response just above background level. In conclusion, the generation of chimeric OC/TR may allow more extended clinical studies of bispecific mAb-mediated immunotherapy of ovarian carcinom