FAIR assessment tools: evaluating use and performance.

Publishing research data using a findable, accessible, interoperable, and reusable (FAIR) approach is paramount to further innovation in many areas of research. In particular in developing innovative approaches to predict (eco)toxicological risks in (nano or advanced) material design where efficient use of existing data is essential. The use of tools assessing the FAIRness of data helps the future improvement of data FAIRness and therefore their re-use. This paper reviews ten FAIR assessment tools that have been evaluated and characterized using two datasets from the nanomaterials and microplastics risk assessment domain. The tools were grouped into four categories: online and offline self-assessment survey based, online (semi-) automated and other tools. We found that the online self-assessment tools can be used for a quick scan of a user's dataset due to their ease of use, little need for experience and short time investment. When a user is looking to assess full databases, and not just datasets, for their FAIRness, (semi-)automated tools are more practical. The offline assessment tools were found to be limited and unreliable due to a lack of guidance and an under-developed state. To further characterize the usability, two datasets were run through all tools to check the similarity in the tools' results. As most of the tools differ in their implementation of the FAIR principles, a large variety in outcomes was obtained. Furthermore, it was observed that only one tool gives recommendations to the user on how to improve the FAIRness of the evaluated dataset. This paper gives clear recommendations for both the user and the developer of FAIR assessment tools.

Correlates of observing and willingness to report stigma towards HIV clients by (TB) health workers in Africa.

SETTING: Health care facilities in Kenya, Tanzania and Namibia. OBJECTIVE: To study the factors associated with the observation of and willingness to report stigmatising behaviour towards persons living with the human immunodeficiency virus (HIV) among health care workers (HCWs). DESIGN: Mixed-effect logistic regression analyses of 9516 HCW interviews, including those of 4062 (43%) TB workers carried out as part of the Service Provision Assessments (SPAs) between 2006 and 2010. RESULT: Discrimination (i.e., enacted stigma) was observed by respectively 1042 (60%), 384 (40%) and 907 (69%) TB workers in Kenya, Namibia and Tanzania, similar to the trend observed among all HCWs. Observations of discrimination were clustered at facility level in Kenya, and mapping of facility-level discrimination suggested geographic clustering. HCWs were more likely to observe discrimination in facilities without regular supportive supervision (adjusted OR [aOR] 2.33, 95%CI 1.09-4.96). No HCW characteristics were found to predict intention to report. Training in patients' rights and in confidentiality predisposed HCWs to recognise discrimination (aOR 2.51, 95%CI 1.19-5.28) and the willingness to report it (aOR 2.23, 95%CI 1.11-4.47). Exposure to training in TB infection control (IC) was associated with greater willingness to report discrimination (aOR 2.13, 95%CI 1.03-4.39). CONCLUSION: Supervision and exposure to training in patient's rights and confidentiality improved HCWs' understanding and advocacy of dignified and respectful TB-HIV care. All HCWs are equally likely to be allies, agents of change and amplifiers of an anti-stigma message, and broad engagement is required. Innovative approaches to reduce discrimination-while ensuring proper IC-should be explored.

Using 15 DHS surveys to study epidemiological correlates of TB courtesy stigma and health-seeking behaviour.

SETTING: Tuberculosis (TB) stigma is thought to delay or prevent the decision to seek health care, but the strength of this association and the prevalence of anticipated TB stigma in the general population in most countries is unknown. OBJECTIVE: To examine epidemiological, cultural and sociodemographic factors associated with TB courtesy stigma in 15 surveys across 13 countries, and its link to health seeking for cough in children under five. DESIGN: A multilevel survey weighted logistic regression model was used to analyse how individual characteristics and social contexts affect the occurrence of TB courtesy stigma. The same modelling approach was used to analyse associations between TB courtesy stigma and individual-level predictors of health-seeking behaviour of mothers for children with cough. RESULTS: TB courtesy stigma varies greatly among countries. TB courtesy stigma was negatively correlated with knowledge of TB's curability (adjusted OR [aOR] 0.82; 95%CI 0.78-0.86) and human immunodeficiency virus (HIV) accepting attitudes (proxy for HIV stigma) (aOR 0.15, 95%CI 0.15-0.16). Mothers' health-seeking behaviour for children under five with cough was found to be positively correlated with HIV accepting attitudes (OR 1.16, 95%CI 1.08-1.25), but was marginally affected by TB courtesy stigma (OR 0.99, 95%CI 0.98-1.00). CONCLUSION: Improving the general awareness of the effectiveness of anti-tuberculosis treatment will help to diminish TB courtesy stigma, and should be prioritised over expanding knowledge of mode of transmission. Efforts to reduce HIV and TB stigma may increase care seeking for childhood TB symptoms.

Defining the research agenda to measure and reduce tuberculosis stigmas.

Crucial to finding and treating the 4 million tuberculosis (TB) patients currently missed by national TB programmes, TB stigma is receiving well-deserved and long-delayed attention at the global level. However, the ability to measure and evaluate the success of TB stigma-reduction efforts is limited by the need for additional tools. At a 2016 TB stigma-measurement meeting held in The Hague, The Netherlands, stigma experts discussed and proposed a research agenda around four themes: 1) drivers: what are the main drivers and domains of TB stigma(s)?; 2) consequences: how consequential are TB stigmas and how are negative impacts most felt?; 3) burden: what is the global prevalence and distribution of TB stigma(s) and what explains any variation? 4): intervention: what can be done to reduce the extent and impact of TB stigma(s)? Each theme was further subdivided into research topics to be addressed to move the agenda forward. These include greater clarity on what causes TB stigmas to emerge and thrive, the difficulty of measuring the complexity of stigma, and the improbability of a universal stigma 'cure'. Nevertheless, these challenges should not hinder investments in the measurement and reduction of TB stigma. We believe it is time to focus on how, and not whether, the global community should measure and reduce TB stigma.

Quantitative risk assessment of the aggregate dermal exposure to the sensitizing fragrance geraniol in personal care products and household cleaning agents.

A quantitative risk assessment was performed to establish if consumers are at risk for being dermally sensitized by the fragrance geraniol. Aggregate dermal exposure to geraniol was estimated using the Probabilistic Aggregate Consumer Exposure Model, containing data on the use of personal care products and household cleaning agents. Consumer exposure to geraniol via personal care products appeared to be higher than via household cleaning agents. The hands were the body parts receiving the highest exposure to geraniol. Dermal sensitization studies were assessed to derive the point of departure needed for the estimation of the Acceptable Exposure Level (AEL). Two concentrations were derived, one based on human studies and the other from dose-response analysis of the available murine local lymph node assay data. The aggregate dermal exposure assessment resulted in body part specific median exposures up to 0.041 µg/cm(2) (highest exposure 102 µg/cm(2)) for hands. Comparing the exposure to the lowest AEL (55 µg/cm(2)), shows that a range of 0.02-0.86% of the population may have an aggregated exposure which exceeds the AEL. Furthermore, it is demonstrated that personal care products contribute more to the consumer's geraniol exposure compared to household cleaning agents.

Bioaccessibility of vitamin A, vitamin C and folic acid from dietary supplements, fortified food and infant formula.

In the Netherlands, vitamin intake occurs mainly via food and for some vitamins also via fortified food. In addition, some people take dietary supplements. Information on the bioavailability of vitamins is important for a good estimation of the actual exposure to vitamins. Furthermore, for a reliable intake estimation, it is important to know the accurateness of the claimed vitamin concentration on the product label. In the current study, the amount of vitamin A, vitamin C, and folic acid in different products and their maximum bioavailability (bioaccessibility) were investigated. In about half of the products, the amount of vitamins significantly deviated from the declared amounts. The vitamin bioaccessibility ranged from <1% to 100%. When assessing the dietary intake exposure of vitamins, it is important to take into account both the possible deviation from the declared level and (the variability of) the bioaccessibility of the vitamin in the products.

Dioxin and dioxin-like PCB exposure of non-breastfed Dutch infants.

The exposure of humans to PCDD/Fs (polychlorinated dibenzo-p-dioxins and dibenzofurans) and dioxin-like PCBs (dl-PCBs, i.e. polychlorinated non-ortho and mono-ortho biphenyls) occurs predominantly via the intake of food. Young children have a relatively high intake of these substances, due to their high food consumption per kilogram body weight. As the exposure of non-breastfed infants to these compounds has not been assessed before in The Netherlands, we studied the dietary intake of 17 PCDD/Fs and 11 dioxin-like PCBs in 188 Dutch non-breastfed infants between 4 and 13 months. The food intake of the infants was assessed by a 2-d food record. From these data PCDD/F and dioxin-like PCB intake was calculated using PCDD/F and dioxin-like PCB concentrations of food products sampled in 1998/1999 in The Netherlands. The long-term PCDD/F and dioxin-like PCB exposure of the infants was calculated using the statistical exposure model (STEM). For infants of 5 months the chronic exposure to PCDD/F and dioxin-like PCB was 1.1pg WHO-TEQ (toxic equivalents) per kilogram body weight (bw) per day (95th percentile: 1.7pg WHO-TEQ/kg bwxd), which mainly originated from infant formula and vegetables and increased to 2.3pg WHO-TEQ/kg bwxd (95th percentile 3.7pg WHO-TEQ/kg bwxd) for infants just over 1 year old eating the same food as their parents. The percentage of formula-fed infants with an exposure exceeding the TDI of 2pg WHO-TEQ/kg bwxd was 5% at 5 months, 49% at 9 months and 64% at 12 months.

High prevalence of vasomotor reflex impairment in newly diagnosed leprosy patients.

BACKGROUND: Initial nerve damage in leprosy occurs in small myelinated and unmyelinated nerve fibers. Early detection of leprosy in the peripheral nervous system is challenging as extensive nerve damage may take place before clinical signs of leprosy become apparent. PATIENTS AND METHODS: In order to determine the prevalence of, and factors associated with, peripheral autonomic nerve dysfunction in newly diagnosed leprosy patients, 76 Brazilian patients were evaluated prior to treatment. Skin vasomotor reflex was tested by means of laser Doppler velocimetry. Blood perfusion and reflex vasoconstriction following an inspiratory gasp were registered on the second and fifth fingers. RESULTS: Vasomotor reflex was impaired in at least one finger in 33/76 (43%) patients. The fifth fingers were more frequently impaired and suffered more frequent bilateral alterations than the second fingers. Multivariate regression analysis showed that leprosy reaction (adjusted odds ratio = 8.11, 95% confidence interval: 1.4-48.2) was associated with overall impaired vasomotor reflex (average of the four fingers). In addition, palmar erythrocyanosis and an abnormal upper limb sensory score were associated with vasomotor reflex impairment in the second fingers, whereas anti-phenolic glycolipid-I antibodies, ulnar somatic neuropathy and a low finger skin temperature were associated with impairment in the fifth fingers. CONCLUSIONS: A high prevalence of peripheral autonomic dysfunction as measured by laser Doppler velocimetry was observed in newly diagnosed leprosy patients, which is clinically evident late in the disease. Autonomic nerve lesion was more frequent than somatic lesions and was strongly related to the immune-inflammatory reaction against M. leprae.

Epidemiology of leprosy on five isolated islands in the Flores Sea, Indonesia

We conducted a population-based survey on 5 small island in South Sulawesi Province (Indonesia) to collect baseline data previous to a chemoprophylactic intervention study aiming at interrrupting the transmission of Mycobacterium leprae. Here we describe the present leprosy epidemiology on these geographically isolated islands. Of the 4774 inhabitants living in the study area 4140 were screened for leprosy (coverage: 87%). We identified 96 leprosy patients (85 new and 11 old patients), representing a new case detection rate (CDR) of 205/10,000 and prevelence rate 195/10,000. CDRs were similar for males and females. Male patients were more often classified as multibacillary (MB) than women. Of the new patients, 33 (39%) were classified as MB, 16 (19%) as paucibacillary (PB) 2-5 lesions and 36 (42%) as PB single lesion. In this area of high leprosy endemicity leprosy patients were extensively clustered, i.e. not equally distributed among the islands and within the islands among the houses

Population survey to determine risk factors for Mycobacterium leprae transmission and infection

Background: Not every leprosy patient is equally effective in transmitting Mycobacterium leprae. We studied the spatial distribution of infection (using seropositivity as a marker) in the population to identifity which disease characteristics of leprosy patients are important in transmission. Methods: Clinical data and blood samples for anti-M.leprae ELISA were collected during a cross-sectional survey on five Indonesian islands highly endemic for leprosy. A geographic information system (GIS) was used to define contacts of patients. We investigated spatial clustering of patients and seropositive people and used logist regression to determine risk factors for seropositivity. Results: Of the 3986 people examined for leprosy, 3271 gave blood. Seroprevalence varied between islands (1.7-8.7%) and correlated significantly with leprosy prevalence. Five clusters of patients and two clusters of seropositives were detected. In multivariate analysis, seropositivity significantly differed to be the best discriminator of contact groups with higher seroprevalence: contacts of seropositive patients had an adjusted odds ratio (aOR) of 1.75 (95% CI: 0.92-3,31). This increased seroprevalence was strongest for contact groups living _< 75 metres of two seropositive patients (aOR:3.07;95%CI:1.74-5.42). Conclusions: In this highly endemic area for leprosy, not only household contacts of seropositive patients, but also persons living in the vicinity of seropositive patient were more likely to harbour antibodies against M.leprae. Through measuring the serological status of patients and using a broader definition of contacts, higher risk groups can be more specifically identified

Genetic, household and spatial clustering of leprosy in an island population in Indonesia

It is generally accepted that genetic factors play a role in susceptibility to both leprosy per se and leprosy type, but the strength of this effects has never been quantified. Estimating the contribution of genetic factors to clustering of leprosy within families is difficult since these persons often shave the same environment. Three correlation structures (genetic, household and spatial) were proposed for population data (n=560), collected on a geographically isolated Indonesian island highly endemic for leprosy, to explain the distribution of leprosy per se, leprosy type and Mycobacterium leprae-specific antibody. Heritability estimates and risk ratios for siblings were calculated to quantify the genetic effect. Leprosy was clinically diagnosed and specific anti-M.leprae antibodies were measured using ELISA. For leprosy per se in the total population the genetic correlation structure fitted best. In the population with relative stable household status (persons under 21 years and above 39 years) all structures were significant. For multibacillary leprosy (MB) genetic factors seemed more important than for paucibacillary leprosy. Seropositivity could be explained best by the apatial model, but the genetic model was also significant. Herediatry was 57% for leprosy per se and 31% for seropositivity. Genetic factors seem to play an important role in the clustering of leprosy patients, especially MB patients, and they could explain more then half of the toral phenotypic variance. This unique study population is very suitable to confirm the role of already known chromosome regions in controlling leprosy or to search for new susceptibility loci

Risk factores for developing leprosy -A population-based cohort study in Indonesia

This study identified risk factors for developing leprosy through yearly incidence rates in five island populations. Personal factors, like age, sex, household size and the presence of M.leprae-specific antibodies as well as contact were studied. Of the 94 index patients (patients diagnosed in 2000) 43 (46%) were classified as multibacillary (MB), 17 (19%) were seropositive and 6 (7%) presented M.leprae DNA in nasal swabs as determined by polumerase chain reaction (PCR). All PCR positive patients were also seropositive. Forty-four of the 4903 persons initially without symptoms of leprosy developed leprosy in almost four years follow-up, giving an incidence rate of 2.98 per 1000 person-years. Men had a 2.2 times higher risk (95% Confidence Interval [CI]: 1.2-4.1) to developd leprosy than women. Persons living in households of more than 7 household members. Persons who were seropositive in 2000 had a 3.7 times higher risk (95% CI:1.1-12.4) than seronegative persons. Household contacts of MB patients had an adjusted hazard ratio (aHR) of 4.6 (95% CI:1.6-12.9) and household contacts of PCR positive patients an aHR of 9.36 (95% CI: 2.5-34.9) compared to non-contacts. Patients with PCR positive nasal swabs, suggesting nasal excretion of M.leprae, are probably the patients with the highest transmission patential. Since all index patients who were PCR positive were also seropositive, serology semms an adequate tool to identify these patients. Preventing seropositive persons to become seropositive patients and thus the main source of infection may break the chain of transmission

Prevention of leprosy using rifampicin as chemoprophylaxis

An intervention study was implemented on five Indinesian island highly endemic for leprosy to determine whether rifampicin can be used as chemoprophylaxis to prevent leprosy. The population was actively screened before the intervention and subsequently once a year for three years. In the control group, no chemoprophylaxis was given. In the contact group, chemoprophylaxis was only given to contacts of leprosy patients and in the blanket group to all aligible persons. The cohort consited of 3,965 persons. The yearly incidence rate in the control group was 39/10,000; the cumulative incidence after three years was significantly lower in the blanket group (P=0.031). No difference was found between the contact and the control groups (P=0.93). Whether this apparent reduced leprosy incidence in the first three years in the blanket group is due to a delayed development of leprosy or a complete clearence of infections needs to be determined

Dioxins, dioxin-like PCBs and non-dioxin-like PCBs in foodstuffs: occurrence and dietary intake in The Netherlands.

Data on occurrence of dioxins (polychlorinated dibenzo-p-dioxins [PCDDs] and dibenzofurans [PCDFs]), dioxin-like PCBs (polychlorinated non-ortho and mono-ortho biphenyls) and non-dioxin-like PCBs (as represented by the so-called indicator-PCBs: congeners 28, 52, 101, 118, 138, 153 and 180) in food products consumed in The Netherlands that were collected in measurement programs carried out during 1998 and 1999, and combined with food consumption data to assess the dietary intake of these persistent food contaminants. The estimated median life-long-averaged intake of the sum of dioxins and dioxin-like PCBs in the population is 1.2 pg WHO-TEQ (toxic equivalents) per kg body weight (bw) per day, while the estimated median life-long-averaged intake of indicator-PCBs is 5.6 ng per kg bw per day. The contribution of different food groups to the total intake of both dioxins + dioxin-like PCBs and non-dioxin-like PCBs is fairly uniformly distributed over the foods consumed: meat products (23% and 27%, respectively), dairy products (27% and 17%, respectively), fish (16% and 26%, respectively), eggs (4% and 5%, respectively), vegetable products (13% and 7%, respectively), and industrial oils and fats (17% and 18%, respectively). Compared with earlier intake estimations the present estimation shows a continued reduction in the intake of dioxins as well as PCBs. This reduction is related to the decrease in the concentration of these substances in the majority of foodstuffs. Nevertheless, a small part of the population still has a rather high life-long averaged intake: 8% of the population is exposed to intake levels above the tolerable weekly intake for dioxins and dioxin-like PCBs of 14 pg WHO-TEQ per kg bw per week, as recently derived by the Scientific Committee on Food of the European Commission. For the non-dioxin-like PCBs an internationally accepted maximum intake level is still lacking. However, to provide risk managers with a health-based guideline to prevent health effects of exposure to non-dioxin-like PCBs, the (international) derivation of a tolerable daily intake is recommended. Monitoring the dietary intake of PCBs is just as important as monitoring the intake of dioxins and dioxin-like PCBs, and attempts to decrease the exposure to both compound classes need continuous attention.

Localization of deposited polycyclic aromatic hydrocarbons in leaves of Plantago.

After deposition to foliage, polycyclic aromatic hydrocarbons (PAHs) may remain on the leaf surface, accumulate in the cuticular wax, or diffuse into the remaining interior of the plant. In a field study, the location of deposited PAHs in the leaves of two Plantago species was determined. To this aim, leaves of Plantago major and Plantago media were divided into three fractions. First, the leaves were washed (wash-off fraction), then cuticular wax was extracted (wax fraction). Finally, the remaining leaf material was extracted (interior fraction). The presence of PAHs could be demonstrated in all three fractions. For both plants, the distribution of PAHs over the three fractions changed with molecular weight (mol wt) of the PAHs. The wash-off fraction increased with increasing molecular weight, likely because high molecular-weight PAHs occur predominantly bound to particles, which can be readily washed off from the leaves. In contrast, the amount of PAHs detected in the interior of the leaves decreased with increasing molecular weight. This can be explained by a slow desorption of the PAHs from the particles and a low diffusion rate of the larger molecules. This study shows that washing reduces the amount of high molecular-weight PAHs on plant surfaces. Therefore, washing of leafy vegetables is important to minimize human dietary intake of PAHs.

Polycyclic aromatic hydrocarbons in soil and plant samples from the vicinity of an oil refinery.

Soil samples, and samples of leaves of Plantago major (great plantain) and grass (mixed species) were collected from the vicinity of an oil refinery in Zelzate, Belgium, and analysed for seven polycyclic aromatic hydrocarbons (PAHs). The samples from the site adjacent to the refinery (site 1) contained very high total PAH-concentrations: namely 300, 8 and 2 microg/g dry wt. for soil, P. major and grass, respectively. Concentrations in samples from more remote sites (up to 4 km from the refinery) were a factor of 10-30 lower than those from site 1, but between them the differences were small. The PAH-profiles of the plant samples, in contrast with those of the soil samples, appeared to shift to higher contributions of gaseous PAHs with increasing distance from the refinery. This can be explained by particle-bound PAHs being deposited closer to the source than gaseous PAHs. It is suggested that particle-bound deposition is relatively more important for deposition to soil than to plants, due to blow-off and wash-off of the compounds from the leaves. The total PAH-concentrations in the leaves of P. major were higher than those measured in the grass samples, probably due to differences in aerodynamic surface roughness, leaf orientation and/or leaf age. However, the concentration ratios of P. major/grass were not constant for the different sites, varying from 1.2 to 8.8. Therefore, it appears that a precise prediction of PAH-concentrations for one plant species from known concentrations of another species is not possible. When errors in predicted concentrations need to be smaller than a factor of approximately 10, the sampling strategy has to be focussed on all species of interest.

Aflatoxin and liver cancer in Sudan.

This study investigated whether aflatoxin contamination of peanut products may contribute to the incidence of hepatocellular carcinoma (HCC) in Sudan. Thirty-seven peanut butter and peanut samples were collected from local markets. Aflatoxin concentrations were significantly higher in West Sudan [87.4 +/- 197.3 (SD) micrograms/kg], a high-risk area, than in Central Sudan (8.5 +/- 6.8 micrograms/kg), a low-risk area. In West Sudan, humid local storage conditions of peanut products were related to high aflatoxin concentrations. In a small case-control study of HCC patients (n = 24) and controls (n = 34), an odds ratio of 7.5 (95% confidence interval = 1.4-40.2) was observed for humid vs. dry local storage conditions. Development of an index of individual HCC exposure was less successful, probably because of year-to-year variability in aflatoxins in food. These preliminary findings justify further research into the role of aflatoxins and hepatitis in HCC incidence in Sudan.

New membrane formation and intercellular communication in the early Xenopus embryo.

The ionic permeability of the nonjunctional and newly formed junctional membranes was investigated in embryos of Xenopus laevis up to the onset of the fifth cleavage. Continuous measurements were made of the equivalent nonjunctional (R'o) and junctional resistances (R'i) in different pairs of adjacent cells separated by one of the four cleavage membranes formed in that period. The specific resistance of the nonjunctional membranes (ro) and of each cleavage membrane (ri) as a function of time were derived using a generally applicable computer simulation model. ro decreased from about 40 komega cm2 in the in the uncleaved egg to about 10 komega cm2 at the 16-cell stage, due to the insertion of a small fraction of the relatively permeable newly formed cleavage membranes into the outer surface. Superimposed on this overall decline, a transient decrease of ro was observed during each cycle, caused by a temporary partial separation of the peripheral parts of adjacent blastomeres. The changes in followed the same pattern. R'1 increased stepwise during each cleavage cycle. At the onset of each cleavage there were no significant differences in R'i as measured between different pairs of cells. After an initial phase of membrane formation ri of all cleavage membranes remained constant at about 400 omega cm2. In the states investigated the coupling ratio ranged from 0.8 to 1. It is argued that this close coupling could be the result of the highly impermeable outer surface even in the absence of specialized junctions in the intercellular membranes.