A survey of a population-based sample of U.S adults was conducted to measure their attitudes about, and inform the design of the Precision Medicine Initiative's planned national cohort study.
An ...online survey was conducted by GfK between May and June of 2015. The influence of different consent models on willingness to share data was examined by randomizing participants to one of eight consent scenarios.
Of 4,777 people invited to take the survey, 2,706 responded and 2,601 (54% response rate) provided valid responses. Most respondents (79%) supported the proposed study, and 54% said they would definitely or probably participate if asked. Support for and willingness to participate in the study varied little among demographic groups; younger respondents, LGBT respondents, and those with more years of education were significantly more likely to take part if asked. The most important study incentive that the survey asked about was learning about one's own health information. Willingness to share data and samples under broad, study-by-study, menu and dynamic consent models was similar when a statement about transparency was included in the consent scenarios. Respondents were generally interested in taking part in several governance functions of the cohort study.
A large majority of the U.S. adults who responded to the survey supported a large national cohort study. Levels of support for the study and willingness to participate were both consistent across most demographic groups. The opportunity to learn health information about one's self from the study appears to be a strong motivation to participate.
The mossy fiber (MF) pathway is critical to hippocampal function and influenced by gonadal hormones. Physiological data are limited, so we asked whether basal transmission and long-term potentiation ...(LTP) differed in slices of adult male and female rats. The results showed small sex differences in basal transmission but striking sex differences in opioid receptor sensitivity and LTP. When slices were made from females on proestrous morning, when serum levels of 17β-estradiol peak, the nonspecific opioid receptor antagonist naloxone (1 μm) enhanced MF transmission but there was no effect in males, suggesting preferential opioid receptor-dependent inhibition in females when 17β-estradiol levels are elevated. The μ-opioid receptor (MOR) antagonist Cys2,Tyr3,Orn5,Pen7-amide (CTOP; 300 nm) had a similar effect but the δ-opioid receptor (DOR) antagonist naltrindole (NTI; 1 μm) did not, implicating MORs in female MF transmission. The GABAB receptor antagonist saclofen (200 μm) occluded effects of CTOP but the GABAA receptor antagonist bicuculline (10 μm) did not. For LTP, a low-frequency (LF) protocol was used because higher frequencies elicited hyperexcitability in females. Proestrous females exhibited LF-LTP but males did not, suggesting a lower threshold for synaptic plasticity when 17β-estradiol is elevated. NTI blocked LF-LTP in proestrous females, but CTOP did not. Electron microscopy revealed more DOR-labeled spines of pyramidal cells in proestrous females than males. Therefore, we suggest that increased postsynaptic DORs mediate LF-LTP in proestrous females. The results show strong MOR regulation of MF transmission only in females and identify a novel DOR-dependent form of MF LTP specific to proestrus.
OBJECTIVES:To describe the quality of physician-family communication during interpreted and noninterpreted family meetings in the PICU.
DESIGN:Prospective, exploratory, descriptive observational ...study of noninterpreted English family meetings and interpreted Spanish family meetings in the pediatric intensive care setting.
SETTING:A single, university-based, tertiary children’s hospital.
SUBJECTS:Participants in PICU family meetings, including medical staff, family members, ancillary staff, and interpreters.
INTERVENTIONS:Thirty family meetings (21 English and nine Spanish) were audio-recorded, transcribed, de-identified, and analyzed using the qualitative method of directed content analysis.
MEASUREMENTS AND MAIN RESULTS:Quality of communication was analyzed in three ways1) presence of elements of shared decision-making, 2) balance between physician and family speech, and 3) complexity of physician speech. Of the 11 elements of shared decision-making, only four occurred in more than half of English meetings, and only three occurred in more than half of Spanish meetings. Physicians spoke for a mean of 20.7 minutes, while families spoke for 9.3 minutes during English meetings. During Spanish meetings, physicians spoke for a mean of 14.9 minutes versus just 3.7 minutes of family speech. Physician speech complexity received a mean grade level score of 8.2 in English meetings compared to 7.2 in Spanish meetings.
CONCLUSIONS:The quality of physician-family communication during PICU family meetings is poor overall. Interpreted meetings had poorer communication quality as evidenced by fewer elements of shared decision-making and greater imbalance between physician and family speech. However, physician speech may be less complex during interpreted meetings. Our data suggest that physicians can improve communication in both interpreted and noninterpreted family meetings by increasing the use of elements of shared decision-making, improving the balance between physician and family speech, and decreasing the complexity of physician speech.
Association studies implicate multiple PDZ domain protein (MPDZ/MUPP1) sequence and/or expression in risk for alcoholism in humans and ethanol withdrawal (EW) in mice, but confirmation has been ...hindered by the dearth of targeted genetic models. We report the creation of transgenic (MPDZ‐TG) and knockout heterozygote (Mpdz+/−) mice, with increased (2.9‐fold) and decreased (53%) target expression, respectively. Both models differ in EW compared with wild‐type littermates (P ≤ 0.03), providing compelling evidence for an inverse relationship between Mpdz expression and EW severity. Additionally, ethanol consumption is reduced up to 18% (P = 0.006) in Mpdz+/−, providing the first evidence implicating Mpdz in ethanol self‐administration.
Association studies implicate the multiple PDZ domain protein in risk for alcoholism in humans and ethanol withdrawal (EW) in mice, but confirmation has been hindered by the dearth of targeted genetic models. We created transgenic (TG) and knock‐out heterozygote (Mpdz+/‐) mice with increased and decreased Mpdz expression, respectively. Both differ in EW compared to wild‐type littermates, providing compelling evidence for an inverse relationship between Mpdz expression and EW severity. We also report data that implicate Mpdz in ethanol reward.
Here, we map a quantitative trait locus (QTL) with a large effect on predisposition to barbiturate (pentobarbital) withdrawal to a 0.44 Mb interval of mouse chromosome 1 syntenic with human 1q23.2. ...We report a detailed analysis of the genes within this interval and show that it contains 15 known and predicted genes, 12 of which demonstrate validated genotype-dependent transcript expression and/or nonsynonymous coding sequence variation that may underlie the influence of the QTL on withdrawal. These candidates are involved in diverse cellular functions including intracellular trafficking, potassium conductance and spatial buffering, and multimolecular complex dynamics, and indicate both established and novel aspects of neurobiological response to sedative-hypnotics. This work represents a substantial advancement toward identification of the gene(s) that underlie the phenotypic effects of the QTL. We identify Kcnj9 as a particularly promising candidate and report the development of a Kcnj9-null mutant model that exhibits significantly less severe withdrawal from pentobarbital as well as other sedative-hypnotics (zolpidem and ethanol) versus wild-type littermates. Reduced expression of Kcnj9, which encodes GIRK3 (Kir3.3), is associated with less severe sedative-hypnotic withdrawal. A multitude of QTLs for a variety of complex traits, including diverse responses to sedative-hypnotics, have been detected on distal chromosome 1 in mice, and as many as four QTLs on human chromosome 1q have been implicated in human studies of alcohol dependence. Thus, our results will be primary to additional efforts to identify genes involved in a wide variety of behavioral responses to sedative-hypnotics and may directly facilitate progress in human genetics.
Alcoholism is a complex clinical disorder with genetic and environmental contributions. Although no animal model duplicates alcoholism, models for specific factors, such as the withdrawal syndrome, ...are useful to identify potential genetic determinants of liability in humans. Murine models have been invaluable to identify quantitative trait loci (QTLs) that influence a variety of alcohol responses. However, the QTL regions are typically large, at least initially, and contain numerous genes, making identification of the causal quantitative trait gene(s) (QTGs) challenging. Here, we present QTG identification strategies currently used in the field of alcohol genetics and discuss relevance to alcoholic human populations.
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