Avidity Bias Research Articles

On the shuttling across the blood-brain barrier via tubule formation: Mechanism and cargo avidity bias.

The blood-brain barrier is made of polarized brain endothelial cells (BECs) phenotypically conditioned by the central nervous system (CNS). Although transport across BECs is of paramount importance for nutrient uptake as well as ridding the brain of waste products, the intracellular sorting mechanisms that regulate successful receptor-mediated transcytosis in BECs remain to be elucidated. Here, we used a synthetic multivalent system with tunable avidity to the low-density lipoprotein receptor-related protein 1 (LRP1) to investigate the mechanisms of transport across BECs. We used a combination of conventional and super-resolution microscopy, both in vivo and in vitro, accompanied with biophysical modeling of transport kinetics and membrane-bound interactions to elucidate the role of membrane-sculpting protein syndapin-2 on fast transport via tubule formation. We show that high-avidity cargo biases the LRP1 toward internalization associated with fast degradation, while mid-avidity augments the formation of syndapin-2 tubular carriers promoting a fast shuttling across.

Assessing average somatic CAG repeat instability at the protein level

Sandwich ELISA-based methods use Abs that target the expanded polyglutamine (polyQ) tract to quantify mutant huntingtin (mHTT). Using Meso Scale Discovery (MSD) assay, the mHTT signal detected with MW1 Ab correlated with polyQ length and doubled with a difference of only 7 glutamine residues between equivalent amounts of purified mHTTexon1 proteins. Similar polyQ length-dependent effects on MSD signals were confirmed using endogenous full length mHTT from brains of Huntington’s disease (HD) knock-in (KI) mice. We used this avidity bias to devise a method to assess average CAG repeat instability at the protein level in a mixed population of HTT proteins present in tissues. Signal detected for average polyQ length quantification at the protein level by our method exhibited a strong correlation with average CAG repeat length at the genomic DNA level determined by PCR method in striatal tissue homogenates from HdhQ140 KI mice and in human HD postmortem cortex. This work establishes that CAG repeat instability in mutant HTT is reflected at the protein level.

Comparison of Self-Reported Telephone Interviewing and Web-Based Survey Responses: Findings From the Second Australian Young and Well National Survey.

BackgroundWeb-based self-report surveying has increased in popularity, as it can rapidly yield large samples at a low cost. Despite this increase in popularity, in the area of youth mental health, there is a distinct lack of research comparing the results of Web-based self-report surveys with the more traditional and widely accepted computer-assisted telephone interviewing (CATI).ObjectiveThe Second Australian Young and Well National Survey 2014 sought to compare differences in respondent response patterns using matched items on CATI versus a Web-based self-report survey. The aim of this study was to examine whether responses varied as a result of item sensitivity, that is, the item’s susceptibility to exaggeration on underreporting and to assess whether certain subgroups demonstrated this effect to a greater extent.MethodsA subsample of young people aged 16 to 25 years (N=101), recruited through the Second Australian Young and Well National Survey 2014, completed the identical items on two occasions: via CATI and via Web-based self-report survey. Respondents also rated perceived item sensitivity.ResultsWhen comparing CATI with the Web-based self-report survey, a Wilcoxon signed-rank analysis showed that respondents answered 14 of the 42 matched items in a significantly different way. Significant variation in responses (CATI vs Web-based) was more frequent if the item was also rated by the respondents as highly sensitive in nature. Specifically, 63% (5/8) of the high sensitivity items, 43% (3/7) of the neutral sensitivity items, and 0% (0/4) of the low sensitivity items were answered in a significantly different manner by respondents when comparing their matched CATI and Web-based question responses. The items that were perceived as highly sensitive by respondents and demonstrated response variability included the following: sexting activities, body image concerns, experience of diagnosis, and suicidal ideation. For high sensitivity items, a regression analysis showed respondents who were male (beta=−.19, P=.048) or who were not in employment, education, or training (NEET; beta=−.32, P=.001) were significantly more likely to provide different responses on matched items when responding in the CATI as compared with the Web-based self-report survey. The Web-based self-report survey, however, demonstrated some evidence of avidity and attrition bias.ConclusionsCompared with CATI, Web-based self-report surveys are highly cost-effective and had higher rates of self-disclosure on sensitive items, particularly for respondents who identify as male and NEET. A drawback to Web-based surveying methodologies, however, includes the limited control over avidity bias and the greater incidence of attrition bias. These findings have important implications for further development of survey methods in the area of health and well-being, especially when considering research topics (in this case diagnosis, suicidal ideation, sexting, and body image) and groups that are being recruited (young people, males, and NEET).

Addressing Onsite Sampling in Analysis of Recreation Demand: Economic Value and Impact of Visitation to Cape Hatteras National Seashore

AbstractThis article presents a unified approach to correcting for avidity bias due to onsite sampling in estimation of descriptive statistics and recreation demand. We extend the Shaw (1988) correction for avidity bias in demand modeling to the Generalized Negative Binomial model, and we demonstrate the effects of avidity bias on descriptive statistics. Correcting for avidity bias in recreation demand lowers welfare estimates, which are still, however, quite large at $403/household, per trip (2002 USD). Correcting expenditure estimates increases economic impact by 17%, reflecting greater magnitude in spending patterns of less avid users that live further from Cape Hatteras National Seashore.

Social acceptance and population confidence in telehealth in Quebec

BackgroundAccess to healthcare in remote areas is difficult and telehealth could be a promising avenue if accepted by the population. The aim of this study is to assess social acceptance and population confidence in telehealth in the Province of Quebec.MethodsWe conducted a survey using a questionnaire assessing the social acceptance of and confidence level in telehealth. Two strategies were used: 1) paper questionnaires were sent to two hospitals in Quebec; and 2) online questionnaires were randomly sent by a firm specialized in online survey to a representative sample of the population of the Province of Quebec. Respondents were all residents of the Province of Quebec and 18 years and older. Questions were scored with a four-level Likert scale.ResultsA total of 1816 questionnaires were analyzed (229 written and 1,587 online questionnaires). The socio-demographic variables in our samples, especially the online questionnaires, were fairly representative of Quebec’s population. Overall, social acceptance scored at 77.71% and confidence level at 65.76%. Both scores were higher in the case of treatment (3 scenarios were proposed) vs. diagnosis (p < 0.05). No difference was found when respondents were asked to respond for themselves and for a member of their family, which demonstrates a true interest in telehealth in Quebec. In addition, we found a significant difference (p < 0.05) between written and online questionnaires regarding social acceptance (80.75% vs. 77.33%) and confidence level (74.84% vs. 64.55%). These differences may be due to social desirability or avidity bias in the written questionnaires.ConclusionsOur results suggest that the population in Quebec encourages the development of telehealth for real time diagnosis and long distance treatment for regions deprived of healthcare professionals.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-015-0727-1) contains supplementary material, which is available to authorized users.

Willingness to pay for ovulation induction treatment in case of WHO II anovulation: a study using the contingent valuation method.

ObjectiveTo measure the willingness to pay (WTP) of women aged 18–45 years to receive drug treatment for ovulation induction (ie, the social value of normal cycles of ovulation for a woman of childbearing age) in order to feed the debate about the funding of fertility cares.SettingAn anonymous questionnaire was used over the general population of Quebec.ParticipantsA total of 136 subjects were recruited in three medical clinics, and 191 subjects through an online questionnaire.MethodThe questionnaire consisted of three parts: introduction to the problematic, socioeconomic data collection to determine factors influencing the formation of WTP, and a WTP question using the simple bid price dichotomous choice elicitation technique. The econometric estimation method is based on the “random utility theory.” Each subject responding to our questionnaire could express her uncertainty about the answer to our WTP question by choosing the answer “I do not know.”Outcome measureThe WTP in Canadian dollars of women aged 18–45 years to receive drug treatment for ovulation induction.ResultsResults are positive and indicate an average WTP exceeding 4,800 CAD, which is much more than the drug treatment cost. There is no evidence of sample frame bias or avidity bias across the two survey modes that cannot be controlled in econometric estimates.ConclusionMedical treatment for ovulation induction is highly socially desirable in Quebec.

Economic Value and Impact of Visitation to Cape Hatteras National Seashore: Addressing Onsite Sampling

We examine recreation demand, economic value, and visitor expenditure patterns for Cape Hatteras National Seashore (CHNS) on the Outer Banks, North Carolina. CHNS is one of the largest protected barrier islands on the East Coast and is remote, accessible only by ferry or a single stretch of road running along the island chain. We present a unified approach to correcting for avidity bias due to onsite sampling in descriptive statistics and demand modeling, extending the Shaw (1988) correction to the Generalized Negative Binomial model. We demonstrate the effects of avidity bias in descriptive statistics; correcting expenditure estimates increases economic impact by 17%, reflecting larger magnitude in spending patterns of less avid users that live further from CNHS. Correcting for avidity bias in recreation demand lowers welfare estimates, which are still, however, quite large at $403/household, per trip (2002 USD).

Addressing onsite sampling in recreation site choice models

Independent experts and politicians have criticized statistical analyses of recreation behavior, which rely upon onsite samples due to their potential for biased inference. The use of onsite sampling usually reflects data or budgetary constraints, but can lead to two primary forms of bias in site choice models. First, the strategy entails sampling site choices rather than sampling individuals—a form of bias called endogenous stratification. Under these conditions, sample choices may not reflect the site choices of the true population. Second, exogenous attributes of the individuals sampled onsite may differ from the attributes of individuals in the population—the most common form in recreation demand is avidity bias. We propose addressing these biases by combining two the existing methods: Weighted Exogenous Stratification Maximum Likelihood estimation and propensity score estimation. We use the National Marine Fisheries Service's Marine Recreational Fishing Statistics Survey to illustrate methods of bias reduction, employing both simulated and empirical applications. We find that propensity score based weights can significantly reduce bias in estimation. Our results indicate that failure to account for these biases can overstate anglers' willingness to pay for improvements in fishing catch, but weighted models exhibit higher variance of parameter estimates and willingness to pay.

Addressing Onsite Sampling in Recreation Site Choice Models

Independent experts and politicians have criticized statistical analyses of recreation behavior that rely upon onsite samples due to their potential for biased inference, prompting some to suggest support for these efforts should be curtailed. The use of onsite sampling usually reflects data or budgetary constraints but can lead to two primary forms of bias in site choice models. First, the strategy entails sampling site choices rather than sampling anglers – a form of bias called endogenous stratification. Under these conditions, sample choices may not reflect the site choices of the true population. Second, the exogenous attributes of the recreational users sampled onsite may differ from the attributes of users in the population – the most common form in recreation demand is avidity bias. We propose addressing these biases by combining two existing methods, Weighted Exogenous Stratification Maximum Likelihood Estimation (WESMLE) and propensity score estimation. We use the National Marine Fisheries Service’s (NMFS) Marine Recreational Fishing Statistics Survey (MRFSS) to illustrate methods of bias reduction employing both simulation and empirical applications. We find that propensity score based weights can significantly reduce bias in estimation. Our results indicate that failure to account for these biases can overstate anglers’ willingness to pay for additional fishing catch.

Welfare Measurement Convergence Through Bias Adjustments in General Population and On-Site Surveys: An Application to Water-based Recreation at Lake Sevan, Armenia

This paper compares household survey with on-site survey data for estimating the access value of a unique natural resource using a single-site travel cost model. The household survey model is adjusted for inflated zero observations for respondents who would not visit the site at any observable positive price. The on-site survey model is corrected for truncation and endogenous stratification, the latter being an adjustment for avidity bias. In an application to recreation at Lake Sevan (Armenia), consumer surplus estimates were not statistically different between the household model and the on-site model when zero-inflation and truncation and endogenous stratification are corrected In the respective models. This leads us to believe that either method can be used to derive a consistent welfare measure of access to a recreational site after appropriate adjustments and corrections are made. These results are somewhat reassuring as the choice between household and on-site surveys is often dictated by time and resource availability.