Feasibility and Acceptability of Mindfulness-Based Relapse Prevention and Adjunct Mobile Technology in Rural Communities

While problematic substance use transcends geographic regions, rural communities appear to be especially impacted. More prevalent problematic substance use and associated problems in these areas are exacerbated by lack of consistent access to evidence-based practices. Mindfulness-Based Relapse Prevention (MBRP) combines standard cognitive-behavioral relapse prevention with formal and informal mindfulness training, and may be a novel and effective treatment approach for substance use disorders (SUD) in these isolated areas. The current study explored feasibility and acceptability, and potential differences in variance accounted for by group randomization on substance use and secondary outcomes, between MBRP and treatment as usual (TAU) in a rural treatment setting, as well as the impact of a specially designed mobile application on treatment engagement and enactment. No differences were observed in variance of substance use or secondary outcome by groups; however, participants in TAU vs. MBRP were more likely to drop out of treatment against medical advice. The mobile application did not appear to impact treatment engagement or enactment. Implications and limitations are discussed

Abert’s Squirrel Management in Support of Endangered Mount Graham Red Squirrel Recovery in Arizona

Recovery of the endangered Mount Graham red squirrel (MGRS) will likely be long and challenging. Its limited habitat, isolation to Pinaleño Mountain range, and demographic characteristics restrict its ability to rebound quickly from threats that impact both the squirrel and its habitat. Currently, threats to the MGRS include habitat degradation and loss through high-severity wildfire, fire suppression activities, insect outbreaks, climate change, and human development, and predation, as well as competition with Abert’s squirrels. The most recent wildfire in 2017 impacted over 48,000 acres of already reduced habitat. A critical first step is to protect and manage the remaining population of the MGRS and its habitat. Management includes but is not limited to maintaining and improving the spruce-fir and mixed conifer biomes, while balancing the need to reduce risk of catastrophic wildfire with the needs of the squirrel. The U.S. Department of Agriculture, Animal and Plant Health Inspection Service Wildlife Services is conducting an Abert’s Squirrel Removal Project at the request of the Arizona Game and Fish Department and the U.S. Fish and Wildlife Service (USFWS), in collaboration with a team of Mount Graham red squirrel experts and managers, to reduce the number of Abert’s squirrels in historical MGRS habitat throughout the Pinaleño Mountains to assist in meeting the needs of the USFWS’ 2011 MGRS draft recovery plan. Abert’s squirrel removals are conducted monthly to minimize competition with MGRS

Promoting the Health of Parents & Children: Addressing Perinatal Mental Health by Building Medical Provider Capacity Through Perinatal Psychiatry Access Programs

Mental health conditions are the most common obstetric complications of the perinatal period, impacting 1 in 5 individuals during pregnancy and the year following pregnancy. Perinatal mental health (PMH) conditions have deleterious effects on the health of perinatal individuals and their children, and are a leading and preventable cause of maternal mortality. Nevertheless, PMH conditions are underrecognized, underdiagnosed, and undertreated. To address these gaps, Massachusetts created the Massachusetts Child Psychiatry Access Program (MCPAP) for Moms to build the capacity of frontline medical providers to address PMH conditions by providing education, consultation, and resources and referrals. MCPAP for Moms has emerged as a successful and scalable model with at least 25 states or organizations implementing or developing similar Perinatal Psychiatry Access Programs. This report summarizes the Perinatal Psychiatry Access Program model and its individual and national impact

Nonlocal Field Theories and their Gravity Duals

The gravity duals of nonlocal field theories in the large N limit exhibit a novel behavior near the boundary. To explore this, we present and study the duals of dipole theories - a particular class of nonlocal theories with fundamental dipole fields. The nonlocal interactions are manifest in the metric of the gravity dual and type-0 string theories make a surprising appearance. We compare the situation to that in noncommutative SYM.Comment: 34pp LaTeX, minor corrections, reference adde

The Intriguing Effects of Substituents in the N-Phenethyl Moiety of Norhydromorphone: A Bifunctional Opioid from a Set of “Tail Wags Dog” Experiments

This work is licensed under a Creative Commons Attribution 4.0 International License.(−)-N-Phenethyl analogs of optically pure N-norhydromorphone were synthesized and pharmacologically evaluated in several in vitro assays (opioid receptor binding, stimulation of [35S]GTPγS binding, forskolin-induced cAMP accumulation assay, and MOR-mediated β-arrestin recruitment assays). “Body” and “tail” interactions with opioid receptors (a subset of Portoghese’s message-address theory) were used for molecular modeling and simulations, where the “address” can be considered the “body” of the hydromorphone molecule and the “message” delivered by the substituent (tail) on the aromatic ring of the N-phenethyl moiety. One compound, N-p-chloro-phenethynorhydromorphone ((7aR,12bS)-3-(4-chlorophenethyl)-9-hydroxy-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one, 2i), was found to have nanomolar binding affinity at MOR and DOR. It was a potent partial agonist at MOR and a full potent agonist at DOR with a δ/μ potency ratio of 1.2 in the ([35S]GTPγS) assay. Bifunctional opioids that interact with MOR and DOR, the latter as agonists or antagonists, have been reported to have fewer side-effects than MOR agonists. The p-chlorophenethyl compound 2i was evaluated for its effect on respiration in both mice and squirrel monkeys. Compound 2i did not depress respiration (using normal air) in mice or squirrel monkeys. However, under conditions of hypercapnia (using air mixed with 5% CO2), respiration was depressed in squirrel monkeys.NIDA grant P30 DA13429NIDA grant DA039997NIDA grant DA018151NIDA grant DA035857NIDA grant DA047574NIH Intramural Research Programs of the National Institute on Drug AbuseNational Institute of Alcohol Abuse and AlcoholismNIH Intramural Research Programs of the National Institute on Drug AbuseNIH Intramural Research Program through the Center for Information TechnologyNIH Intramural Research Programs of the National Institute on Drug Abus

Population Genomic Inferences from Sparse High-Throughput Sequencing of Two Populations of Drosophila melanogaster

Short-read sequencing techniques provide the opportunity to capture genome-wide sequence data in a single experiment. A current challenge is to identify questions that shallow-depth genomic data can address successfully and to develop corresponding analytical methods that are statistically sound. Here, we apply the Roche/454 platform to survey natural variation in strains of Drosophila melanogaster from an African (n = 3) and a North American (n = 6) population. Reads were aligned to the reference D. melanogaster genomic assembly, single nucleotide polymorphisms were identified, and nucleotide variation was quantified genome wide. Simulations and empirical results suggest that nucleotide diversity can be accurately estimated from sparse data with as little as 0.2× coverage per line. The unbiased genomic sampling provided by random short-read sequencing also allows insight into distributions of transposable elements and copy number polymorphisms found within populations and demonstrates that short-read sequencing methods provide an efficient means to quantify variation in genome organization and content. Continued development of methods for statistical inference of shallow-depth genome-wide sequencing data will allow such sparse, partial data sets to become the norm in the emerging field of population genomics

Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci

Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: Rs13422522 (NYAP2; P = 8.87 × 10-11), rs12454712 (BCL2; P = 2.7 × 10-8), and rs10506418 (FAM19A2; P = 1.9 × 10-8). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci

Transcription Factors Bind Thousands of Active and Inactive Regions in the Drosophila Blastoderm

Identifying the genomic regions bound by sequence-specific regulatory factors is central both to deciphering the complex DNA cis-regulatory code that controls transcription in metazoans and to determining the range of genes that shape animal morphogenesis. We used whole-genome tiling arrays to map sequences bound in Drosophila melanogaster embryos by the six maternal and gap transcription factors that initiate anterior–posterior patterning. We find that these sequence-specific DNA binding proteins bind with quantitatively different specificities to highly overlapping sets of several thousand genomic regions in blastoderm embryos. Specific high- and moderate-affinity in vitro recognition sequences for each factor are enriched in bound regions. This enrichment, however, is not sufficient to explain the pattern of binding in vivo and varies in a context-dependent manner, demonstrating that higher-order rules must govern targeting of transcription factors. The more highly bound regions include all of the over 40 well-characterized enhancers known to respond to these factors as well as several hundred putative new cis-regulatory modules clustered near developmental regulators and other genes with patterned expression at this stage of embryogenesis. The new targets include most of the microRNAs (miRNAs) transcribed in the blastoderm, as well as all major zygotically transcribed dorsal–ventral patterning genes, whose expression we show to be quantitatively modulated by anterior–posterior factors. In addition to these highly bound regions, there are several thousand regions that are reproducibly bound at lower levels. However, these poorly bound regions are, collectively, far more distant from genes transcribed in the blastoderm than highly bound regions; are preferentially found in protein-coding sequences; and are less conserved than highly bound regions. Together these observations suggest that many of these poorly bound regions are not involved in early-embryonic transcriptional regulation, and a significant proportion may be nonfunctional. Surprisingly, for five of the six factors, their recognition sites are not unambiguously more constrained evolutionarily than the immediate flanking DNA, even in more highly bound and presumably functional regions, indicating that comparative DNA sequence analysis is limited in its ability to identify functional transcription factor targets