Tonic inhibition of accumbal spiny neurons by extrasynaptic 4 GABAA receptors modulates the actions of psychostimulants

Within the nucleus accumbens (NAc), synaptic GABAA receptors (GABAARs) mediate phasic inhibition of medium spiny neurons (MSNs) and influence behavioral responses to cocaine. We demonstrate that both dopamine D1- and D2-receptor-expressing MSNs (D-MSNs) additionally harbor extrasynaptic GABAARs incorporating α4, β, and δ subunits that mediate tonic inhibition, thereby influencing neuronal excitability. Both the selective δ-GABAAR agonist THIP and DS2, a selective positive allosteric modulator, greatly increased the tonic current of all MSNs from wild-type (WT), but not from δ−/− or α4−/− mice. Coupling dopamine and tonic inhibition, the acute activation of D1 receptors (by a selective agonist or indirectly by amphetamine) greatly enhanced tonic inhibition in D1-MSNs but not D2-MSNs. In contrast, prolonged D2 receptor activation modestly reduced the tonic conductance of D2-MSNs. Behaviorally, WT and constitutive α4−/− mice did not differ in their expression of cocaine-conditioned place preference (CPP). Importantly, however, mice with the α4 deletion specific to D1-expressing neurons (α4D1−/−) showed increased CPP. Furthermore, THIP administered systemically or directly into the NAc of WT, but not α4−/− or α4D1−/− mice, blocked cocaine enhancement of CPP. In comparison, α4D2−/− mice exhibited normal CPP, but no cocaine enhancement. In conclusion, dopamine modulation of GABAergic tonic inhibition of D1- and D2-MSNs provides an intrinsic mechanism to differentially affect their excitability in response to psychostimulants and thereby influence their ability to potentiate conditioned reward. Therefore, α4βδ GABAARs may represent a viable target for the development of novel therapeutics to better understand and influence addictive behaviors

Parent Body Influences on Amino Acids in the Tagish Lake Meteorite

The Tagish Lake meteorite is a primitive C2 carbonaceous chondrite with a mineralogy, oxygen isotope, and bulk chemical. However, in contrast to many CI and CM carbonaceous chondrites, the Tagish Lake meteorite was reported to have only trace levels of indigenous amino acids, with evidence for terrestrial L-amino acid contamination from the Tagish Lake meltwater. The lack of indigenous amino acids in Tagish Lake suggested that they were either destroyed during parent body alteration processes and/or the Tagish Lake meteorite originated on a chemically distinct parent body from CI and CM meteorites where formation of amino acids was less favorable. We recently measured the amino acid composition of three different lithologies (11h, 5b, and 11i) of pristine Tagish Lake meteorite fragments that represent a range of progressive aqueous alteration in order 11h < 5b < 11i as inferred from the mineralogy, petrology, bulk isotopes, and insoluble organic matter structure. The distribution and enantiomeric abundances of the one- to six-carbon aliphatic amino acids found in hot-water extracts of the Tagish Lake fragments were determined by ultra performance liquid chromatography fluorescence detection and time of flight mass spectrometry coupled with OPA/NAC derivatization. Stable carbon isotope analyses of the most abundant amino acids in 11h were measured with gas chromatography coupled with quadrupole mass spectrometry and isotope ratio mass spectrometry

The relevance of ERTS-1 data to the state of Ohio

There are no author-identified significant results in this report

Genome-wide association studies for feedlot and growth traits in cattle

A genome wide-association study for production traits in cattle was carried out using genotype data from the 10K Affymetrix (Santa Clara, CA) and the 50K Illumina (San Diego, CA) SNP chips. The results for residual feed intake (RFI), BW, and hip height in 3 beef breed types (Bos indicus, Bos taurus, and B. indicus × B. taurus), and for stature in dairy cattle, are presented. The aims were to discover SNP associated with all traits studied, but especially RFI, and further to test the consistency of SNP effects across different cattle populations and breed types. The data were analyzed within data sets and within breed types by using a mixed model and fitting 1 SNP at a time. In each case, the number of significant SNP was more than expected by chance alone. A total of 75 SNP from the reference population with 50K chip data were significant (P < 0.001) for RFI, with a false discovery rate of 68%. These 75 SNP were mapped on 24 different BTA. Of the 75 SNP, the 9 most significant SNP were detected on BTA 3, 5, 7, and 8, with P ≤ 6.0 × 10 . In a population of Angus cattle divergently selected for high and low RFI and 10K chip data, 111 SNP were significantly (P < 0.001) associated with RFI, with a false discovery rate of 7%. Approximately 103 of these SNP were therefore likely to represent true positives. Because of the small number of SNP common to both the 10K and 50K SNP chips, only 27 SNP were significantly (P < 0.05) associated with RFI in the 2 populations. However, other chromosome regions were found that contained SNP significantly associated with RFI in both data sets, although no SNP within the region showed a consistent effect on RFI. The SNP effects were consistent between data sets only when estimated within the same breed type

Botulinum toxins for the prevention of migraine in adults

BackgroundMigraine occurs in around 15% of adults and is ranked as the seventh most disabling disease amongst all diseases globally. Despite the available treatments many people suffer prolonged and frequent attacks which have a major impact on their quality of life. Chronic migraine is defined as 15 or more days of headache per month, at least eight of those days being migraine. People with episodic migraine have fewer than 15 headache days per month. Botulinum toxin type A has been licensed in some countries for chronic migraine treatment, due to the results of just two trials.ObjectivesTo assess the effects of botulinum toxins versus placebo or active treatment for the prevention or reduction in frequency of chronic or episodic migraine in adults.Search methodsWe searched CENTRAL, MEDLINE & MEDLINE in Process, Embase, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry (to December 2017). We examined reference lists and carried out citation searches on key publications. We sent correspondence to major manufacturers of botulinum toxin.Selection criteriaRandomised, double‐blind, controlled trials of botulinum toxin (any sero‐type) injections into the head and neck for prophylaxis of chronic or episodic migraine in adults. Eligible comparators were placebo, alternative prophylactic agent or different dose of botulinum toxin.Data collection and analysisTwo review authors independently selected trials and extracted data. For continuous outcomes we used mean change data when available. For dichotomous data we calculated risk ratios (RRs). We used data from the 12‐week post‐treatment follow‐up time point. We assessed the evidence using GRADE and created two 'Summary of findings' tables.Main resultsDescription of trialsWe found 90 articles describing 28 trials (4190 participants), which were eligible for inclusion. The longest treatment duration was three rounds of injections with three months between treatments, so we could not analyse long‐term effects. For the primary analyses, we pooled data from both chronic and episodic participant populations. Where possible, we also separated data into chronic migraine, episodic migraine and ‘mixed group’ classification subgroups. Most trials (21 out of 28) were small (fewer than 50 participants per trial arm). The risk of bias for included trials was low or unclear across most domains, with some trials reporting a high risk of bias for incomplete outcome data and selective outcome reporting.Botulinum toxin versus placeboTwenty‐three trials compared botulinum toxin with placebo. Botulinum toxin may reduce the number of migraine days per month in the chronic migraine population by 3.1 days (95% confidence interval (CI) ‐4.7 to ‐1.4, 4 trials, 1497 participants, low‐quality evidence). This was reduced to ‐2 days (95% CI ‐2.8 to ‐1.1, 2 trials, 1384 participants; moderate‐quality evidence) when we removed small trials.A single trial of people with episodic migraine (N = 418) showed no difference between groups for this outcome measure (P = 0.49).In the chronic migraine population, botulinum toxin reduces the number of headache days per month by 1.9 days (95% CI ‐2.7 to ‐1.0, 2 trials, 1384 participants, high‐quality evidence). We did not find evidence of a difference in the number of migraine attacks for both chronic and episodic migraine participants (6 trials, N = 2004, P = 0.30, low‐quality evidence). For the population of both chronic and episodic migraine participants a reduction in severity of migraine rated during clinical visits, on a 10 cm visual analogue scale (VAS) of 3.3 cm (95% CI ‐4.2 to ‐2.5, very low‐quality evidence) in favour of botulinum toxin treatment came from four small trials (N = 209); better reporting of this outcome measure from the additional eight trials that recorded it may have improved our confidence in the pooled estimate. Global assessment and quality‐of‐life measures were poorly reported and it was not possible to carry out statistical analysis of these outcome measures. Analysis of adverse events showed an increase in the risk ratio with treatment with botulinum toxin over placebo 30% (RR 1.28, 95% CI 1.12 to 1.47, moderate‐quality evidence). For every 100 participants 60 experienced an adverse event in the botulinum toxin group compared with 47 in the placebo group.Botulinum toxin versus other prophylactic agentThree trials studied comparisons with alternative oral prophylactic medications. Meta‐analyses were not possible for number of migraine days, number of headache days or number of migraine attacks due to insufficient data, but individually trials reported no differences between groups for a variety of efficacy measures in the population of both chronic and episodic migraine participants. The global impression of disease measured using Migraine Disability Assessment (MIDAS) scores were reported from two trials that showed no difference between groups. Compared with oral treatments, botulinum toxin showed no between‐group difference in the risk of adverse events (2 trials, N = 114, very low‐quality evidence). The relative risk reduction (RRR) for withdrawing from botulinum toxin due to adverse events compared with the alternative prophylactic agent was 72% (P = 0.02, 2 trials, N = 119).Dosing trialsThere were insufficient data available for the comparison of different doses.Quality of the evidenceThe quality of the evidence assessed using GRADE methods was varied but mostly very low; the quality of the evidence for the placebo and active control comparisons was low and very low, respectively for the primary outcome measure. Small trial size, high risk of bias and unexplained heterogeneity were common reasons for downgrading the quality of the evidence.Authors' conclusionsIn chronic migraine, botulinum toxin type A may reduce the number of migraine days per month by 2 days compared with placebo treatment. Non‐serious adverse events were probably experienced by 60/100 participants in the treated group compared with 47/100 in the placebo group. For people with episodic migraine, we remain uncertain whether or not this treatment is effective because the quality of this limited evidence is very low. Better reporting of outcome measures in published trials would provide a more complete evidence base on which to draw conclusions

A More Reduced Mantle Source for Enriched Shergottites; Insights from the Olivine-Phyric Shergottite Lar 06319

A detailed petrographic study of melt inclusions and Cr-Fe-Ti oxides of LAR 06319 leads to two main conclusions: 1) this enriched oxidized olivine- phyric shergottite represents nearly continuous crystallization of a basaltic shergottite melt, 2) the melt became more oxidized during differentiation. The first crystallized mineral assemblages record the oxygen fugacity which is closest to that of the melt s mantle source, and which is lower than generally attributed to the enriched shergottite group

The fast response of volcano-seismic activity to intense precipitation: Triggering of primary volcanic activity by rainfall at Soufrière Hills Volcano, Montserrat

One-minute resolution time series of rainfall and seismic data from the Soufriere Hills Volcano, Montserrat are analysed to explore the mechanism of external forcing of volcanic eruptions by rainfall over three years of activity. The real-time seismic amplitude (RSAM) shows a narrow, statistically significant, peak within 30 min after the start of intense rainfall events, and a much broader peak with a lag of 6?40 h. The classified seismic events indicate that the volcanic response to rainfall begins at the surface and gradually penetrates deeper into the dome, as there is an increase in the pseudo-magnitude of: surface rockfall events (including pyroclastic flows) with lags from the first 30 min to 40 h, long-period rockfalls (from shallow degassing) at lags of 4 and 14 h, and long-period and hybrid events (source depth approximately 1 km) with lags at 14 and 24 h after the start of rainfall events. There was no rainfall-related change in deeper, volcano-tectonic activity. There was no change in the frequency of any type of classified event, indicating that the rainfall acts to modulate existing, internal processes, rather than generating new events itself. These robust results are due to many (229) different rainfall events, and not just to a few, large magnitude cases. The rainfalltriggered volcanic activity examined here is consistent with a model of fast, shallow interactions with rainfall at the dome surface, after which, a deeper dome collapse follows

Rates of Emotional Disturbance Among Children in Foster Care: Comparing Federal Child Welfare Data and Medicaid Records in Two States

The purpose of this study is to estimate the rate of emotional disturbance (ED) among children in foster care and assess the validity of the national foster care census data (AFCARS) measure of ED. This study used linked child protection and Medicaid records from 2014 and 2015, for the states of California and Wisconsin, as well as data from AFCARS, a federal population census of children in foster care which states are mandated to contribute to. ED is defined by AFCARS and includes an array of mental and behavioral health diagnoses. According to AFCARS, 13% of CA children in foster care and 15% of WI children in foster care had an ED, whereas Medicaid claims produce rates of 45% and 48%, respectively. Rates of ED among children in congregate care were underestimated by 43?46 percentage points, with substantial proportions having diagnoses of disruptive behavioral disorders. Despite the AFCARS ED measure being cited in congressional testimonies and its wide use in research, results from this study suggest that the AFCARS ED estimates are an unreliable metric for use in research, policy, or practice

Unusual features in the nonlinear microwave surface impedance of Y-Ba-Cu-O thin films

Striking features have been found in the nonlinear microwave (8 GHz) surface impedance $Z_s=R_s + jX_s$ of high-quality YBaCuO thin films with comparable low power characteristics [$R_{res}\sim 35--60 \mu\Omega$ and $\lambda_L(15 K)\sim 130--260 nm$]. The surface resistance $R_s$ is found to increase, decrease, or remain independent of the microwave field $H_{rf}$ (up to 60 mT) at different temperatures and for different samples. However, the surface reactance $X_s$ always follows the same functional form. Mechanisms which may be responsible for the observed variations in $R_s$ and $X_s$ are briefly discussed.Comment: 4 pages, 4 figure

Patient and family experiences of palliative care in hospital: What do we know? An integrative review

Background: In most developed countries, acute hospitals play a significant role in palliative care provision and are the setting in which most people die. They are often the setting where a life-limiting diagnosis is made and where patients present when symptoms develop or when they are not well managed. Understanding the experiences of hospital admissions for people with a life-limiting illness and their families is essential in understanding the role acute hospitals play in providing palliative care. Aim: The aim of this review is to synthesise current evidence regarding the experience of palliative care in an acute hospital setting from the perspectives of patient and family. Design: An integrative review was completed using standard processes followed by a process of data extraction and synthesis. Data sources: Using predefined search terms, literature was sourced from five electronic databases including MEDLINE (EBSCO), CINAHL, EMBASE, Cochrane and PsycINFO between January 1990 and November 2011. Reference lists from relevant articles were cross-checked and pertinent journals hand searched for articles. Results: In total, 32 articles were included in the review. Five recurring themes were identified from the synthesised data: symptom control and burden, communication with health professionals, decision-making related to patient care and management, inadequate hospital environment and interpersonal relationships with health professionals. Conclusion: This review has identified that, largely as a result of study design, our knowledge of patient and family experiences of palliative care in an acute hospital remains limited to discrete aspects of care. Further research is required to explore the total patient and family experience taking into account all aspects of care including the potential benefits of hospital admissions in the last year of life