Longitudinal Policy and Systems Change as a Component of Community Power.

Community power represents the ability of communities to develop, sustain, and grow the capacity to participate in and advance systems change that addresses health inequities but is difficult to assess because of its multifaceted, longitudinal nature. Using California's school-based Local Control Funding Formula (LCFF) as an example, this article examines the interconnectedness of longitudinal policy and systems changes as one approach to understanding and visualizing evolving community power. Data on policy and systems changes were collected during the 10-year, place-based Building Healthy Communities initiative and coded using thematic analysis. Related changes within sites and between community and state levels were linked to show how changes built and overlapped over time. Around 45% of changes were interconnected and cascaded to build momentum within sites; in addition, a substantial proportion of statewide changes (68%) overlapped with community ones. The state-level LCFF policy led to multiple community-based changes over time, involving ongoing engagement from various community groups across communities. Local implementation of the LCFF policy change was used to illustrate the usefulness of connecting community-driven policy and systems changes over time to explore the dynamics of community power and address some of the limitations of that approach.

Polymer Stabilization of Uniform Lying Helix Texture in a Bimesogen-Doped Cholesteric Liquid Crystal for Frequency-Modulated Electro-Optic Responses.

A polymer network (PN) can sustain the uniform lying helix (ULH) texture in a binary cholesteric liquid crystal (LC) comprising a calamitic LC and a bimesogenic LC dimer. Upon copolymerization of a bifunctional monomer with a trifunctional monomer at a concentration of 5 wt% to create the desired polymer network structure, the PN-ULH was obtained with high stability and recoverability even when cycles of helical unwinding-to-rewinding processes were induced after the electrical or thermal treatment. Utilizing dielectric spectroscopy, the flexoelectric-polarization-dominated dielectric relaxation in the PN-ULH state was characterized to determine two frequency regions, f < fflexo and f > fdi, with pronounced and suppressed flexoelectric effect, respectively. It is demonstrated that the cell in the PN-ULH state can operate in the light-intensity modulation mode by the flexoelectric and dielectric effects at f < fflexo and phase-shift mode by the dielectric effect at f > fdi. Moreover, varying the voltage frequency from f < fflexo to f > fdi results in a frequency dispersion of transmittance analogous to that of flexoelectric-polarization-dominated dielectric relaxation. The unique combination of the bimesogen-doped cholesteric LC with a stable and recoverable PN-ULH texture is thus promising for developing a frequency-modulated electro-optic device.

Withdrawal severity after chronic intermittent ethanol in inbred mouse strains.

BACKGROUND: To study withdrawal, ethanol is usually administered chronically without interruption. However, interest has recurred in models of episodic exposure. Increasing evidence suggests that chronic intermittent exposure to ethanol leads to a sensitization effect in both withdrawal severity and ethanol consumption. The goal of the present study was to examine mouse inbred strain differences in withdrawal severity following chronic intermittent exposure using the handling-induced convulsion as the behavioral endpoint. We also sought to compare the withdrawal responses of inbred strains across acute, chronic continuous, and chronic intermittent exposure regimens. METHODS: Male mice from 15 standard inbred strains were exposed to ethanol vapor for 16 hours each day for 3 days and removed to an air chamber during the intervening 8 hours. Mice in the control groups were handled the same, except that they were exposed only to air. Daily blood ethanol concentrations were averaged for each mouse to estimate total dose of ethanol experienced. RESULTS: Across strains, mice had an average daily blood ethanol concentration (BEC) of 1.45 +/- 0.02 mg/ml and we restricted the range of this value to 1.00-2.00 mg/ml. To evaluate strain differences, we divided data into two dose groups based on BEC, low dose (1.29 +/- 0.1 mg/ml) and high dose (1.71 +/- 0.02 mg/ml). After the third inhalation exposure, ethanol-exposed and air-exposed groups were tested hourly for handling-induced convulsions for 10 hour and at hour 24 and 25. Strains differed markedly in the severity of withdrawal (after subtraction of air control values) in both dose groups. CONCLUSION: The chronic intermittent exposure paradigm is sufficient to elicit differential withdrawal responses across nearly all strains. Data from the high-dose groups correlated well with withdrawal data derived from prior acute (single high dose) and chronic continuous (for 72 hours) ethanol withdrawal studies, supporting the influence of common genes on all three responses.

A method for mapping intralocus interactions influencing excessive alcohol drinking.

Excessive alcohol (ethanol) consumption is the hallmark of alcohol use disorders. The F1 hybrid cross between the C57BL/6J (B6) and FVB/NJ (FVB) inbred mouse strains consumes more ethanol than either progenitor strain. The purpose of this study was to utilize ethanol-drinking data and genetic information to map genes that result in overdominant (or heterotic) ethanol drinking. About 600 B6 x FVB F2 mice, half of each sex, were tested for ethanol intake and preference in a 24-h, two-bottle water versus ethanol choice procedure, with ascending ethanol concentrations. They were then tested for ethanol intake in a Drinking in the Dark (DID) procedure, first when there was no water choice and then when ethanol was offered versus water. DNA samples were obtained and genome-wide QTL analyses were performed to search for single QTLs (both additive and dominance effects) and interactions between pairs of QTLs, or epistasis. On average, F2 mice consumed excessive amounts of ethanol in the 24-h choice procedure, consistent with high levels of consumption seen in the F1 cross. Consumption in the DID procedure was similar or higher than amounts reported previously for the B6 progenitor. QTLs resulting in heightened consumption in heterozygous compared to homozygous animals were found on Chrs 11, 15, and 16 for 24-h choice 30% ethanol consumption, and on Chr 11 for DID. No evidence was found for epistasis between any pair of significant or suggestive QTLs. This indicates that the hybrid overdominance is due to intralocus interactions at the level of individual QTL.

A line of mice selected for high blood ethanol concentrations shows drinking in the dark to intoxication.

BACKGROUND: Many animal models of alcoholism have targeted aspects of excessive alcohol intake (abuse) and dependence. In the rodent, models aimed at increasing alcohol self-administration have used genetic or environmental manipulations, or their combination. Strictly genetic manipulations (e.g., comparison of inbred strains or targeted mutants, selective breeding) have not yielded rat or mouse genotypes that will regularly and voluntarily drink alcohol to the point of intoxication. Although some behavioral manipulations (e.g., scheduling or limiting access to alcohol, adding a sweetener) will induce mice or rats to drink enough alcohol to become intoxicated, these typically require significant food or water restriction or a long time to develop. We report progress toward the development of a new genetic animal model for high levels of alcohol drinking. METHODS: High Drinking in the Dark (HDID-1) mice have been selectively bred for high blood ethanol concentrations (BEC, ideally exceeding 100 mg%) resulting from the ingestion of a 20% alcohol solution. RESULTS: After 11 generations of selection, more than 56% of the population now exceeds this BEC after a 4-hour drinking session in which a single bottle containing 20% ethanol is available. The dose of ethanol consumed also produced quantifiable signs of intoxication. CONCLUSIONS: These mice will be useful for mechanistic studies of the biological and genetic contributions to excessive drinking.

Use of a novel mouse genotype to model acute benzodiazepine withdrawal.

Withdrawal from benzodiazepines in physically dependent rodents often requires that the drug be dislodged from its receptor with a competitive antagonist. Withdrawal Seizure-Prone (WSP) mice were selectively bred for their susceptibility to handling-induced withdrawal convulsions following chronic treatment with ethanol. Reflecting pleiotropic genetic influences, they also experience more severe withdrawal from other sedative-hypnotics including the benzodiazepine, diazepam. We used this susceptible genotype to test whether other benzodiazepine receptor (BZR) agonists also produce physical dependence following acute administration, comparing studies of spontaneous withdrawal with those where convulsions were precipitated by a BZR antagonist (flumazenil). Separate groups of mice were tested following a single injection of one of eight BZR agonists. Several doses of each drug were tested for spontaneous withdrawal, and a single dose of each drug was tested for precipitated withdrawal. Withdrawal convulsions were seen after all of the drugs by at least one method, suggesting that BZR agonists as a class elicit acute physical dependence in this susceptible genotype.

Observer-rated ataxia: rating scales for assessment of genetic differences in ethanol-induced intoxication in mice.

Identification of genetic and physiological mechanisms underlying a drug's or mutation's effects on motor performance could be aided by the existence of a simple observation-based rating scale of ataxia for mice. Rating scales were developed to assess ataxia after ethanol (2.75, 3.0, and 3.25 g/kg) in nine inbred mouse strains. Each scale independently rates a single behavior. Raters, blinded to dose, scored four behaviors (splay of hind legs, wobbling, nose down, and belly drag) at each of four time points after injection. The severities of hind leg splaying and wobbling were quantifiable, whereas nose down and belly dragging were expressed in all-or-none fashion. Interrater reliabilities were substantial (0.75 0 at some time), but all doses were equally effective. Incidence of nose down and belly dragging behaviors increased strain dependently after ethanol, but strains did not differentially respond to dose. Ethanol-induced splaying was modestly, and negatively, genetically correlated with wobbling. Nose down and belly dragging tended to be associated with splaying and wobbling at later times. Four distinct ataxia-related behaviors were sensitive to ethanol. Strains differed in ethanol sensitivity for all measures. Modest strain mean correlations among behaviors indicate that these behaviors are probably under control of largely different genes and that ataxia rating scales should rate separate behaviors on discrete scales.

Genotypic differences in ethanol sensitivity in two tests of motor incoordination.

Motor incoordination is frequently used as a behavioral index of intoxication by drugs that depress the central nervous system. Two tasks that have been used to assay incoordination in mice, the balance beam and the grid test, were evaluated to optimize aspects of apparatus and testing procedures for studying genetic differences. Mice of eight inbred strains were given one of several doses of ethanol or saline and tested for intoxication. Strains differed in sensitivity to ethanol in both tests, indicating a significant influence of genotype on ethanol sensitivity. For the balance beam, the width of the beam affected the strain sensitivity pattern, and only the widest beam worked well at all doses. For the grid test, both ethanol dose and the time after drug injection affected strains differentially. Although the behavioral sign of intoxication recorded for both tests was a foot-slip error, the correlations of strain means for ethanol sensitivity across the two tasks were generally not significant. This suggests that the genes influencing ethanol sensitivity in the two tasks are mostly different. These results make clear that a single set of task parameters is insufficient to characterize genetic influences on behavior. Several other issues affect the interpretation of data using these tests.