Obtaining data linkage consent for children: factors influencing outcomes and potential biases

Understanding factors associated with consent for data linkage has largely focussed on adults, but parents or guardians can also be asked to consent on behalf of children for whom they are responsible. A framework for consent decision is presented, and is tested using a large nationally representative survey asking mothers to consent for both themselves and their children for two sets of records. Nearly all mothers give the same consent outcome for all their children. Consent rates are higher for education records than for health records and higher for mothers than children. Multivariate analyses suggest that minorities are generally less likely to consent, while more trust increases chances of consent. Several survey environment factors are important, with harder-to-contact respondents less likely to consent, while the presence of others and higher interviewer-respondent rapport lead to a higher chance of consent. These findings suggest potential methodologies to improve consent rates and possibly minimise bias. This is important given significant demographic differences between children across consent outcomes. However, data from a survey of 10?15 year olds in the study shows fewer differences for several important behaviours and attitudes across consent outcomes

Self-esteem instability and affective instability in everyday life after remission from borderline personality disorder

Background: Borderline personality disorder (BPD) is defined by a pervasive pattern of instability. According to prior findings and clinical theories, self-esteem instability and affective instability are key features of BPD. Previous e-diary studies showed that instability in self-esteem is heightened and that it is highly intertwined with affective instability in BPD in comparison to healthy controls (HC). The present study sought to extend these findings by adding symptomatologically remitted BPD patients (BPD-REM), i.e. former patients with BPD who met four or fewer BPD criteria within the past year, as a comparison group. Methods: To examine differences regarding self-esteem instability and affective instability, we used e-diaries for repeatedly collecting data on self-esteem, valence, and tense arousal 12 times a day for four consecutive days while participants underwent their daily life activities. Determining three different state-of-the-art instability indices and applying multilevel analyses, we compared 35 BPD-REM participants with previously reported 60 acute BPD patients (BPD-ACU) and 60 HC. Results: Our results revealed that self-esteem instability was significantly lower in the BPD-REM compared to the BPD-ACU group, irrespective of the instability index. In contrast, there were no significant differences regarding affective instability between the BPD-REM participants and those in the BPD-ACU group. The comparison between the BPD-REM with the HC indicated both a significantly higher instability in self-esteem as well as significantly heightened affective instability in the BPD-REM participants. Moreover, even though the associations were not significant, we found tentative support for the assumption that affective changes that are accompanied by changes in self-esteem are experienced as more burdensome and negatively impact the quality of life of remitted BPD participants. Conclusions: This study builds on growing evidence for the importance of self-esteem instability in BPD. Whereas affective instability has been reported in various psychiatric disorders and might indeed constitute a transdiagnostic marker of affective dysregulation, our results indicate that self-esteem instability might be a specific symptom that construes the unique pathology in BPD

Propensity to consent to data linkage: experimental evidence on the role of three survey design features in a UK longitudinal panel

When performing data linkage, survey respondents need to provide their informed consent. Since not all respondents agree to this request, the linked data-set will have fewer observations than the survey data-set alone and bias may be introduced. By focusing on the role that survey design features play in gaining respondents’ consent, this paper provides an innovative contribution to the studies in this field. Analysing experimental data collected in a nationally representative household panel survey of the British population, we find that interview features such as question format (dependent/independent questions) and placement of the consent question within the questionnaire have an impact on consent rates

The influence of Ga+^+-irradiation on the transport properties of mesoscopic conducting thin films

We studied the influence of 30keV Ga$^+$-ions -- commonly used in focused ion beam (FIB) devices -- on the transport properties of thin crystalline graphite flake, La$_{0.7}$Ca$_{0.3}$MnO$_3$ and Co thin films. The changes of the electrical resistance were measured in-situ during irradiation and also the temperature and magnetic field dependence before and after irradiation. Our results show that the transport properties of these materials strongly change at Ga$^+$ fluences much below those used for patterning and ion beam induced deposition (IBID), limiting seriously the use of FIB when the intrinsic properties of the materials of interest are of importance. We present a method that can be used to protect the sample as well as to produce selectively irradiation-induced changes.Comment: 14 pages, 11 figures, will be published in Nanotechnology 201

An optimized single chain TCR scaffold relying on the assembly with the native CD3-complex prevents residual mispairing with endogenous TCRs in human T-cells.

Immunotherapy of cancer envisions the adoptive transfer of T-cells genetically engineered with tumor-specific heterodimeric α/β T-cell receptors (TCRα/β). However, potential mispairing of introduced TCRα/β-chains with endogenous β/α-ones may evoke unpredictable autoimmune reactivities. A novel single chain (sc)TCR format relies on the fusion of the Vα-Linker-Vβ-fragment to the TCR Cβ-domain and coexpression of the TCR Cα-domain capable of recruiting the natural CD3-complex for full and hence, native T-cell signaling. Here, we tested whether such a gp100(280-288)- or p53(264-272) tumor antigen-specific scTCR is still prone to mispairing with TCRα. In a human Jurkat-76 T-cell line lacking endogenous TCRs, surface expression and function of a scTCR could be reconstituted by any cointroduced TCRα-chain indicating mispairing to take place on a molecular basis. In contrast, transduction into human TCRα/β-positive T-cells revealed that mispairing is largely reduced. Competition experiments in Jurkat-76 confirmed the preference of dcTCR to selfpair and to spare scTCR. This also allowed for the generation of dc/scTCR-modified cytomegalovirus/tumor antigen-bispecific T-cells to augment T-cell activation in CMV-infected tumor patients. Residual mispairing was prevented by strenghtening the Vα-Li-Vβ-fragment through the design of a novel disulfide bond between a Vα- and a linker-resident residue close to Vβ. Multimer-stainings, and cytotoxicity-, IFNγ-secretion-, and CFSE-proliferation-assays, the latter towards dendritic cells endogenously processing RNA-electroporated gp100 antigen proved the absence of hybrid scTCR/TCRα-formation without impairing avidity of scTCR/Cα in T-cells. Moreover, a fragile cytomegalovirus pp65(495-503)-specific scTCR modified this way acquired enhanced cytotoxicity. Thus, optimized scTCR/Cα inhibits residual TCR mispairing to accomplish safe adoptive immunotherapy for bulk endogenous TCRα/β-positive T-cells

The Application and Implications of Novel Deterministic Sensitivity Analysis Methods

Deterministic sensitivity analyses (DSA) remain important to interpret the effect of uncertainties in individual parameters on results of cost-effectiveness analyses. Classic DSA methodologies may lead to wrong conclusions due to a lack of or misleading information regarding marginal effects, non-linearity, likelihood and correlations. In addition, tornado diagrams are misleading in some situations. Recent advances in DSA methods have the potential to provide decision makers with more reliable information regarding the effects of uncertainties in individual parameters. This practical application discusses advances to classic DSA methods and their implications. Three methods are discussed: stepwise DSA, distributional DSA and probabilistic DSA. For each method, the technical specifications, options for presenting results, and its implications for decision making are discussed. Options for visualizing DSA results in incremental cost-effectiveness ratios and in incremental net benefits are presented. The use of stepwise DSA increases interpretability of marginal effects and non-linearities in the model, which is especially relevant when arbitrary ranges are implemented. Using the probability distribution of each parameter in distributional DSA provides insight on the likelihood of model outcomes while probabilistic DSA also includes the effects of correlations between parameters. Probabilistic DSA, preferably expressed in incremental net benefit, is the most appropriate method for providing insight on the effect of uncertainty in individual parameters on the estimate of cost effectiveness. However, the opportunities provided by probabilistic DSA may not always be needed for decision making. Other DSA methods, in particular distributional DSA, can sometimes be sufficient depending on model features. Decision makers must determine to which extent they will accept and implement these new and improved DSA methodologies and adjust guidelines accordingly

Psychometric evaluation of the Mental Health Quality of Life (MHQoL) instrument in seven European countries

Introduction: To make efficient use of available resources, decision-makers in healthcare may assess the costs and (health) benefits of health interventions. For interventions aimed at improving mental health capturing the full health benefits is an important challenge. The Mental Health Quality of Life (MHQoL) instrument was recently developed to meet this challenge. Evaluating the pyschometric properties of this instrument in different contexts remains important. Methods: A psychometric evaluation of the MHQoL was performed using existing international, cross-sectional data with 7155 respondents from seven European countries (Denmark, France, Germany, Italy, Portugal, The Netherlands, Portugal and the United Kingdom). Reliability was examined by calculating Cronbach’s alpha, a measure of internal consistency of the seven MHQoL dimensions, and by examining the association of the MHQoL sum scores with the MHQoL-VAS scores. Construct validity was examined by calculating Spearman’s rank correlation coefficients between the MHQoL sum scores and EQ-5D index scores, EQ-VAS scores, EQ-5D anxiety/depression dimension scores, ICECAP-A index scores and PHQ-4 sum scores. Results: The MHQoL was found to have good internal consistency for all seven countries. The MHQoL sum score and the MHQoL-VAS had a high correlation. Spearman’s rank correlation coefficients were moderate to very high for all outcomes. Conclusion: Our results, based on data gathered in seven European countries, suggest that the MHQoL shows favourable psychometrical characteristics. While further validation remains important, the MHQoL may be a useful instrument in measuring mental health-related quality of life in the Western European context

Sexual orientation and symptoms of common mental disorder or low wellbeing: combined meta-analysis of 12 UK population health surveys

Background Previous studies have indicated increased risk of mental disorder symptoms, suicide and substance misuse in lesbian, gay and bisexual (LGB) adults, compared to heterosexual adults. Our aims were to determine an estimate of the association between sexual orientation identity and poor mental health and wellbeing among adults from 12 population surveys in the UK, and to consider whether effects differed for specific subgroups of the population. Methods Individual data were pooled from the British Cohort Study 2012, Health Survey for England 2011, 2012 and 2013, Scottish Health Survey 2008 to 2013, Longitudinal Study of Young People in England 2009/10 and Understanding Society 2011/12. Individual participant meta-analysis was used to pool estimates from each study, allowing for between-study variation. Results Of 94,818 participants, 1.1 % identified as lesbian/gay, 0.9 % as bisexual, 0.8 % as ‘other’ and 97.2 % as heterosexual. Adjusting for a range of covariates, adults who identified as lesbian/gay had higher prevalence of common mental disorder when compared to heterosexuals, but the association was different in different age groups: apparent for those under 35 (OR = 1.78, 95 % CI 1.40, 2.26), weaker at age 35–54.9 (OR = 1.42, 95 % CI 1.10, 1.84), but strongest at age 55+ (OR = 2.06, 95 % CI 1.29, 3.31). These effects were stronger for bisexual adults, similar for those identifying as ‘other’, and similar for 'low wellbeing'. Conclusions In the UK, LGB adults have higher prevalence of poor mental health and low wellbeing when compared to heterosexuals, particularly younger and older LGB adults. Sexual orientation identity should be measured routinely in all health studies and in administrative data in the UK in order to influence national and local policy development and service delivery. These results reiterate the need for local government, NHS providers and public health policy makers to consider how to address inequalities in mental health among these minority groups

Long-term Observations Reveal Environmental Conditions and Food Supply Mechanisms at an Arctic Deep-Sea Sponge Ground

Deep-sea sponge grounds are hotspots of benthic biomass and diversity. To date, very limited data exist on the range of environmental conditions in areas containing deep-sea sponge grounds and which factors are driving their distribution and sustenance. We investigated oceanographic conditions at a deep-sea sponge ground located on an Arctic Mid-Ocean Ridge seamount. Hydrodynamic measurements were performed along Conductivity-Temperature-Depth transects, and a lander was deployed within the sponge ground that recorded near-bottom physical properties as well as vertical fluxes of organic matter over an annual cycle. The data demonstrate that the sponge ground is found at water temperatures of −0.5°C to 1°C and is situated at the interface between two water masses at only 0.7° equatorward of the turning point latitude of semi-diurnal lunar internal tides. Internal waves supported by vertical density stratification interact with the seamount topography and produce turbulent mixing as well as resuspension of organic matter with temporarily very high current speeds up to 0.72 m s−1. The vertical movement of the water column delivers food and nutrients from water layers above and below toward the sponge ground. Highest organic carbon flux was observed during the summer phytoplankton bloom period, providing fresh organic matter from the surface. The flux of fresh organic matter is unlikely to sustain the carbon demand of this ecosystem. Therefore, the availability of bacteria, nutrients, and dissolved and particulate matter, delivered by tidally forced internal wave turbulence and transport by horizontal mean flows, likely plays an important role in meeting ecosystem-level food requirements

Precise Measurement of Sigma Beam Asymmetry for Positive Pion Photoproduction on the Proton from 800 to 1500 Mev

The Sigma beam asymmetry for positive pion photoproduction on the proton has been measured over an angular range of 40-170 deg at photon energies from 0.8 to 1.5 GeV. The resulting data set includes 237 accurate points, 136 of these belonging to an almost unexplored domain above 1.05 GeV. Data of such high precision provide severe constraints for partial wave analyses. The influence of this experiment on the GW multipole analysis is demonstrated. Significant changes are found in multipoles connected to the S31(1620) and P13(1720) resonances. Comparisons using the MAID analysis are also presented.Comment: 11 pages, 4 eps figures. to be published in Physics Letters