OECD workshop consensus report: Ethical considerations with respect to human derived products, specifically human serum, in OECD test guidelines.

The ethical needs and concerns with use and sourcing of human materials, particularly serum, in OECD in vitro test guidelines were explored in a dedicated international workshop held in 2019. The health-related aspects of the donation procedure, including tissue screening, donor health, laboratory work health protection, permission from the donor for commercial use, payment of the donors and the potential for exploitation of low-income populations and data protection of the donors; supply, availability, and competition with clinical needs; traceability of the serum and auditability/GLP needs for the Test Guideline Programme, were examined. Here we provide the recommendations of the workshop with respect to the use of human serum, and potentially other human reagents, specifically with regard to test method development for OECD Test Guideline utility as part of the Mutual Acceptance of Data requirement across all OECD member countries. These include informed donor consent terminology, a checklist of human serum information requirements to be included with the Good Laboratory Practise report, and suitable sources for human serum to ensure waste supplies are used, that can no longer be used for medical purposes, ensuring no competition of supply for essential medical use.

It Takes a (Virtual) Village: Exploring the Role of a Career Community to Support Sensemaking As a Proactive Socialization Practice.

Scholars have long advocated for individuals to play a more proactive role during organizational entry rather than relying on institutionally led processes. The primary benefit being that the newcomer moves from passive recipient, dependent on the institution to highlight relevant information, to active agent with self-determined sources and methods to aid in adjustment. A virtual career community made up of 12 first year business faculty members was created to provide such a self-determined source of support during the transition from doctoral studies to full-time assistant professorship. After the entry period (1 academic year), the interactions in this community were used as data for a phenomenon driven research study. The results illustrate how a virtual career community could be used as a proactive socialization tool by encouraging sensemaking amongst first year faculty peers. The sensemaking process consists of perceived contrasts and tensions, followed by positive and negative self-disclosures, community feedback, and the experience of cognitive-behavioral shifts. The findings also expand the proactive use of external referents during organizational entry, which previously had only looked at friends and family members of the newcomer.

The effect of brand and caloric information on flavor perception and food consumption in restrained and unrestrained eaters.

The goal of the current study was to determine whether provision of brand and caloric information affects sensory perception and consumption of a food in restrained (n=84) and unrestrained eaters (n=104). Using a between-subjects 2 × 2 × 3 design, female restrained and unrestrained eaters were asked to taste and rate a cookie that was labeled with a brand associated with healthful eating (Kashi(®)) or one associated with unhealthful eating (Nabisco(®)). Additionally, some participants were presented with a nutrition label alongside the brand name indicating that one serving contained 130 calories (Low-Calorie Condition), or 260 calories (High-Calorie Condition). The remaining participants were not shown a nutrition label (No Label Condition). Results indicated that those in the No Label or the High-Calorie Condition perceived the healthful branded cookie to have a better flavor than those who received the unhealthful branded cookie regardless of their restraint status. However, restrained eaters in the No Label Condition consumed more of the healthful than the unhealthful branded cookie, whereas those in the Low-Calorie Condition consumed more of the unhealthful than the healthful branded cookie. In contrast, unrestrained eaters ate more of the healthful branded cookie regardless of the caloric information provided. Thus, although restrained and unrestrained eaters' perceptions are similarly affected by branding and caloric information, brands and caloric information interact to affect restrained eaters' consumption. This study reveals that labeling foods as low calorie may create a halo effect which may lead to over-consumption of these foods in restrained eaters.

Variation in immunoreactive trypsinogen concentrations among Michigan newborns and implications for cystic fibrosis newborn screening.

OBJECTIVE: To investigate variation in immunoreactive trypsinogen (IRT) concentrations by race, sex, birth weight, and gestational age and their implications for the use of percentile-based cutoffs for cystic fibrosis (CF) newborn screening (NBS) programs. PATIENTS AND METHODS: This cross-sectional population-based study of resident infants screened in Michigan investigates associations between demographic and perinatal variables and IRT concentrations after controlling for covariates. This study also analyzed how 96th and 99.8th IRT concentration percentiles values calculated by Michigan NBS vary by demographic and perinatal factors. Characteristics of infants having high (≥99.8th percentile) IRT concentrations and negative DNA tests are also explored. RESULTS: IRT mean concentrations and percentiles vary significantly by race, birth weight, gestational age, and to a lesser degree by sex. The greatest variation in mean IRT concentrations was observed among racial categories; black infants had an adjusted mean concentration of 36 ng/ml and Asian/Pacific Islander infants had a mean concentration of 25 ng/ml compared to an average concentration of 28 ng/ml in white infants and infants of other races. CONCLUSIONS: Variation in IRT concentrations resulted in the over-representation of certain groups referred for secondary testing, particularly referrals for sweat testing based on very high (≥99.8th percentile) concentrations alone, which is no longer recommended in Michigan. Further research may be warranted to evaluate initial IRT cutoffs used for CF NBS.

Confirmation and extension of association of blood lead with attention-deficit/hyperactivity disorder (ADHD) and ADHD symptom domains at population-typical exposure levels.

BACKGROUND: Recent studies have suggested that child attention-deficit/hyperactivity disorder (ADHD) and its symptom domains are related to blood lead level, even at background exposure levels typical in western countries. However, recent studies disagreed as to whether lead was related to inattention or hyperactivity-impulsivity within the ADHD domain. More definitive evaluation of these questions was sought. METHODS: Two hundred and thirty-six (236) children aged 6-17 years participated (61 ADHD-Combined type, 47 ADHD Predominantly Inattentive type, 99 non-ADHD control, 29 unclassified borderline, situational, or not otherwise specified (NOS) cases). Formal diagnosis was reliably established by a best estimate procedure based on a semi-structured clinical interview and parent and teacher ratings. Lead was assayed from whole blood using inductively coupled plasma mass spectrometry with a method detection limit of .3 microg/dL. RESULTS: Blood lead levels were slightly below United States and Western Europe population exposure averages, with a mean of .73 and a maximum of 2.2 microg/dL. This is the lowest level of blood lead ever studied in relation to ADHD. After statistical control for covariates including IQ and prenatal smoking exposure, blood lead was associated with ADHD-combined type but not inattentive type. Parent and teacher report indicated association of blood lead with Conners cognitive problems, but only teacher report showed effects on DSM-IV inattention symptoms. Blood lead was associated with hyperactivity-impulsivity in parent report regardless of measurement method, whereas teacher report effects depended on child treatment history. CONCLUSIONS: These findings confirm that in children with typical US population lead exposure, careful identification of children with ADHD also identifies children with slightly elevated blood lead.

Low blood lead levels associated with clinically diagnosed attention-deficit/hyperactivity disorder and mediated by weak cognitive control.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and low-level lead exposure are high-prevalence conditions among children, and studies of large populations have suggested that these conditions are related. We examine this relationship in children from a community sample exposed to average background levels of lead who have a diagnosis of ADHD that is established by clinical criteria. METHODS: One hundred fifty children ages 8-17 years participated (mean age = 14 years; 53 control subjects, 47 ADHD Predominantly Inattentive type, 50 ADHD-Combined type). Diagnosis was formally established with a semi-structured clinical interview and parent and teacher ratings. Children completed intelligence quotient (IQ) measures and the stop task (a neuropsychological measure). Lead was assayed from whole blood with inductively coupled plasma mass spectrometry. RESULTS: Blood lead levels in this sample closely matched US population exposure averages, with a maximum level of 3.4 mug/dL. Blood lead levels were statistically significantly higher in ADHD-combined type than in non-ADHD control (p < .05) children. Blood lead was associated with symptoms of hyperactivity-impulsivity but not inattention-disorganization, after control of covariates. Blood lead levels were linked with a lower IQ (p < .05), but IQ did not account for effects on hyperactivity. Instead, hyperactivity mediated effects of lead on IQ. Effects of blood lead on hyperactivity-impulsivity were mediated by poor performance on the stop task. This mediation effect was independent of effects of lead on IQ. CONCLUSIONS: Low-level lead exposure might be an important contributor to ADHD. Its effects seem to be mediated by less effective cognitive control, consistent with a route of influence via striatal-frontal neural circuits.

Caprine mucopolysaccharidosis IIID: fetal and neonatal brain and liver glycosaminoglycan and morphological perturbations.

Mucopolysaccharidosis IIID (MPS IIID) is a lysosomal storage disease associated with deficient activity of the enzyme N-acetylglucosamine 6-sulfatase (EC 3.1.6.14), a lysosomal hydrolase in the heparan sulfate glycosaminoglycan (HS-GAG) degradation pathway. In caprine MPS IIID, enzyme replacement therapy reversed early postnatal systemic but not primary or secondary central nervous system (CNS) substrate accumulations. The caprine MPS IIID large animal model system was used in this investigation to define the developmental profile of morphological and biochemical perturbations to estimate a time frame for therapeutic intervention. Light and electron microscopy were used to compare the CNS, liver, and kidney of normal +/+, MPS IIID carrier +/-, and MPS IIID-affected -/- goat kids (kids), at 60, 113-114, 128-129, and 135 d gestation (dg) of a 150-d gestational period, at birth, and at 59-64 d of postnatal (d-pn) age. In the CNS of -/- kids, morphological correlations of HS-GAG and glycolipid accumulations were evident in early differentiating neurons at 60 dg. CNS and systemic developmental, regional, and cellular differences in -/- kids at all time points included more prominent and earlier accumulation of lucent, putative HS-GAG substrates in lysosomes of meningeal and perivascular macrophages and hepatic sinusoidal cells than in CNS, hepatic, or renal parenchymal cells. The amounts and compositions of HS-GAG substrates in the brain and liver of +/+, +/-, and -/- kids were determined at 60, 65, 113-114, and 128-135 dg, at birth, and 53-78 d-pn. In the CNS of -/- kids, HS-GAG concentrations were variable and exceeded those of age-matched control tissue samples in the third but not the second trimester. In contrast, hepatic HS-GAG levels in -/- kids exceeded control values at all time points evaluated and paralleled the progressive morphological alterations. CNS and hepatic HS-GAG compositions in -/- kids were similar to each other and were more complex at all pre- and postnatal ages than those from control kids. Based on the time frame of development of CNS lesions and biochemical perturbations, prenatal therapeutic intervention in caprine MPS IIID is likely to be necessary to prevent or ameliorate substantive CNS and systemic lesions.