Medical Marijuana Laws, Traffic Fatalities, and Alcohol Consumption

To date, 16 states have passed medical marijuana laws, yet very little is known about their effects. Using state-level data, we examine the relationship between medical marijuana laws and a variety of outcomes. Legalization of medical marijuana is associated with increased use of marijuana among adults, but not among minors. In addition, legalization is associated with a nearly 9 percent decrease in traffic fatalities, most likely to due to its impact on alcohol consumption. Our estimates provide strong evidence that marijuana and alcohol are substitutes.medical marijuana, traffic fatalities, alcohol consumption

High on Life? Medical Marijuana Laws and Suicide

Using state-level data for the period 1990 through 2007, we estimate the effect of legalizing medical marijuana on suicide rates. Our results suggest that the passage of a medical marijuana law is associated with an almost 5 percent reduction in the total suicide rate, an 11 percent reduction in the suicide rate of 20- through 29-year-old males, and a 9 percent reduction in the suicide rate of 30- through 39-year-old males. Estimates of the relationship between legalization and female suicides are less precise and are sensitive to functional form.medical marijuana laws, marijuana, alcohol, suicide

A Critical Role for Glycine Transporters in Hyperexcitability Disorders

Defects in mammalian glycinergic neurotransmission result in a complex motor disorder characterized by neonatal hypertonia and an exaggerated startle reflex, known as hyperekplexia (OMIM 149400). This affects newborn children and is characterized by noise or touch-induced seizures that result in muscle stiffness and breath-holding episodes. Although rare, this disorder can have serious consequences, including brain damage and/or sudden infant death. The primary cause of hyperekplexia is missense and non-sense mutations in the glycine receptor (GlyR) α1 subunit gene (GLRA1) on chromosome 5q33.1, although we have also discovered rare mutations in the genes encoding the GlyR β subunit (GLRB) and the GlyR clustering proteins gephyrin (GPNH) and collybistin (ARHGEF9). Recent studies of the Na+/Cl−-dependent glycine transporters GlyT1 and GlyT2 using mouse knockout models and human genetics have revealed that mutations in GlyT2 are a second major cause of hyperekplexia, while the phenotype of the GlyT1 knockout mouse resembles a devastating neurological disorder known as glycine encephalopathy (OMIM 605899). These findings highlight the importance of these transporters in regulating the levels of synaptic glycine

Ecophysiological traits of grasses: resolving the effects of photosynthetic pathway and phylogeny

C4 photosynthesis is an important example of convergent evolution in plants, having arisen in eudicots, monocots and diatoms. Comparisons between such diverse groups are confounded by phylogenetic and ecological differences, so that only broad generalisations can be made about the role of C4 photosynthesis in
determining ecophysiological traits. However, 60% of C4 species occur in the grasses (Poaceae) and molecular phylogenetic techniques confirm that there are between 8 and 17 independent origins of C4 photosynthesis in the Poaceae. In a screening experiment, we compared leaf physiology and growth traits across several major
independent C3 & C4 groups within the Poaceae, asking 1) which traits differ consistently between photosynthetic
types and 2) which traits differ consistently between clades within each photosynthetic type

Localization of Glycine Receptors in the Human Forebrain, Brainstem, and Cervical Spinal Cord: An Immunohistochemical Review

Inhibitory neurotransmitter receptors for glycine (GlyR) are heteropentameric chloride ion channels that are comprised of four functional subunits, alpha1–3 and beta and that facilitate fast-response, inhibitory neurotransmission in the mammalian brain and spinal cord. We have investigated the distribution of GlyRs in the human forebrain, brainstem, and cervical spinal cord using immunohistochemistry at light and confocal laser scanning microscopy levels. This review will summarize the present knowledge on the GlyR distribution in the human brain using our established immunohistochemical techniques. The results of our immunohistochemical labeling studies demonstrated GlyR immunoreactivity (IR) throughout the human basal ganglia, substantia nigra, various pontine regions, rostral medulla oblongata and the cervical spinal cord present an intense and abundant punctate IR along the membranes of the neuronal soma and dendrites. This work is part of a systematic study of inhibitory neurotransmitter receptor distribution in the human CNS, and provides a basis for additional detailed physiological and pharmacological studies on the inter-relationship of GlyR, GABAAR and gephyrin in the human brain. This basic mapping exercise, we believe, will provide important baselines for the testing of future pharmacotherapies and drug regimes that modulate neuroinhibitory systems. These findings provide new information for understanding the complexity of glycinergic functions in the human brain, which will translate into the contribution of inhibitory mechanisms in paroxysmal disorders and neurodegenerative diseases such as Epilepsy, Huntington's and Parkinson's Disease and Motor Neuron Disease

Sequence and functional characterization of hypoxia inducible factors, HIF1α, HIF2αa, and HIF3α, from the estuarine fish, Fundulus heteroclitus

Author Posting. © The Author(s), 2016. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in American Journal of Physiology-Regulatory Integrative and Comparative Physiology, 312 (2017): R412-R425, doi:10.1152/ajpregu.00402.2016.The hypoxia inducible factor (HIF) family of transcription factors plays central roles in the development, physiology, pathology, and environmental adaptation of animals. Because many aquatic habitats are characterized by episodes of low dissolved oxygen, fish represent ideal models to study the roles of HIF in the response to aquatic hypoxia. The estuarine fish Fundulus heteroclitus occurs in habitats prone to hypoxia, it responds to low oxygen via behavioral, physiological, and molecular changes, and one member of the HIF family, HIF2α, has been previously described. Herein, cDNA sequencing, phylogenetic analyses, and genomic approaches were used to determine other members of the HIFα family from F. heteroclitus and their relationships to HIFα subunits from other vertebrates. In vitro and cellular approaches demonstrated that full-length forms of HIF1α, 2α, and 3α independently formed complexes with the β subunit (ARNT) to bind to hypoxia response elements and activate reporter gene expression. Quantitative PCR showed that HIFα mRNA abundance varied among organs of normoxic fish in an isoform-specific fashion. Analysis of the F. heteroclitus genome revealed a locus encoding a second HIF2α, HIF2αb, a predicted protein lacking oxygen sensing and transactivation domains. Finally, sequence analyses demonstrated polymorphism in the coding sequence of each F. heteroclitus HIFα subunit, suggesting that genetic variation in these transcription factors may play a role in the variation in hypoxia responses among individuals or populations.This research was supported in part by the National Science Foundation (IBN-0236494 and DEB-1120263) and by National Institute of Environmental Health Sciences (NIEHS) grant P42ES007381 (Superfund Basic Research Program at Boston University). Data interpretation was aided by reference to a preliminary draft of the F. heteroclitus genome sequence, which was supported by funding from the National Science Foundation (collaborative research grants DEB-1120512, DEB-1265282, DEB-1120013, DEB-1120263, DEB-1120333, DEB-1120398)

Obtaining structured clinical data from unstructured data using natural language processing software

ABSTRACT Background Free text documents in healthcare settings contain a wealth of information not captured in electronic healthcare records (EHRs). Epilepsy clinic letters are an example of an unstructured data source containing a large amount of intricate disease information. Extracting meaningful and contextually correct clinical information from free text sources, to enhance EHRs, remains a significant challenge. SCANR (Swansea University Collaborative in the Analysis of NLP Research) was set up to use natural language processing (NLP) technology to extract structured data from unstructured sources. IBM Watson Content Analytics software (ICA) uses NLP technology. It enables users to define annotations based on dictionaries and language characteristics to create parsing rules that highlight relevant items. These include clinical details such as symptoms and diagnoses, medication and test results, as well as personal identifiers.   Approach To use ICA to build a pipeline to accurately extract detailed epilepsy information from clinic letters. Methods We used ICA to retrieve important epilepsy information from 41 pseudo-anonymized unstructured epilepsy clinic letters. The 41 letters consisted of 13 ‘new’ and 28 ‘follow-up’ letters (for 15 different patients) written by 12 different doctors in different styles. We designed dictionaries and annotators to enable ICA to extract epilepsy type (focal, generalized or unclassified), epilepsy cause, age of onset, investigation results (EEG, CT and MRI), medication, and clinic date. Epilepsy clinicians assessed the accuracy of the pipeline. Results The accuracy (sensitivity, specificity) of each concept was: epilepsy diagnosis 98% (97%, 100%), focal epilepsy 100%, generalized epilepsy 98% (93%, 100%), medication 95% (93%, 100%), age of onset 100% and clinic date 95% (95%, 100%). Precision and recall for each concept were respectively, 98% and 97% for epilepsy diagnosis, 100% each for focal epilepsy, 100% and 93% for generalized epilepsy, 100% each for age of onset, 100% and 93% for medication, 100% and 96% for EEG results, 100% and 83% for MRI scan results, and 100% and 95% for clinic date. Conclusions ICA is capable of extracting detailed, structured epilepsy information from unstructured clinic letters to a high degree of accuracy. This data can be used to populate relational databases and be linked to EHRs. Researchers can build in custom rules to identify concepts of interest from letters and produce structured information. We plan to extend our work to hundreds and then thousands of clinic letters, to provide phenotypically rich epilepsy data to link with other anonymised, routinely collected data

Solid-state molecular organometallic chemistry. Single-crystal to single-crystal reactivity and catalysis with light hydrocarbon substrates

Single-crystal to single-crystal solid/gas reactivity and catalysis starting from the precursor sigma-alkane complex [Rh(Cy2PCH2CH2PCy2)(η2η2-NBA)][BArF4] (NBA = norbornane; ArF = 3,5-(CF3)2C6H3) is reported. By adding ethene, propene and 1-butene to this precursor in solid/gas reactions the resulting alkene complexes [Rh(Cy2PCH2CH2PCy2)(alkene)x][BArF4] are formed. The ethene (x = 2) complex, [Rh(Cy2PCH2CH2PCy2)(ethene)2][BArF4]-Oct, has been characterized in the solid-state (single-crystal X-ray diffraction) and by solution and solid-state NMR spectroscopy. Rapid, low temperature recrystallization using solution methods results in a different crystalline modification, [Rh(Cy2PCH2CH2PCy2)(ethene)2][BArF4]-Hex, that has a hexagonal microporous structure (P6322). The propene complex (x = 1) [Rh(Cy2PCH2CH2PCy2)(propene)][BArF4] is characterized as having a π-bound alkene with a supporting γ-agostic Rh⋯H3C interaction at low temperature by single-crystal X-ray diffraction, variable temperature solution and solid-state NMR spectroscopy, as well as periodic density functional theory (DFT) calculations. A fluxional process occurs in both the solid-state and solution that is proposed to proceed via a tautomeric allyl-hydride. Gas/solid catalytic isomerization of d3-propene, H2CCHCD3, using [Rh(Cy2PCH2CH2PCy2)(η2η2-NBA)][BArF4] scrambles the D-label into all possible positions of the propene, as shown by isotopic perturbation of equilibrium measurements for the agostic interaction. Periodic DFT calculations show a low barrier to H/D exchange (10.9 kcal mol-1, PBE-D3 level), and GIPAW chemical shift calculations guide the assignment of the experimental data. When synthesized using solution routes a bis-propene complex, [Rh(Cy2PCH2CH2PCy2)(propene)2][BArF4], is formed. [Rh(Cy2PCH2CH2PCy2)(butene)][BArF4] (x = 1) is characterized as having 2-butene bound as the cis-isomer and a single Rh⋯H3C agostic interaction. In the solid-state two low-energy fluxional processes are proposed. The first is a simple libration of the 2-butene that exchanges the agostic interaction, and the second is a butene isomerization process that proceeds via an allyl-hydride intermediate with a low computed barrier of 14.5 kcal mol-1. [Rh(Cy2PCH2CH2PCy2)(η2η2-NBA)][BArF4] and the polymorphs of [Rh(Cy2PCH2CH2PCy2)(ethene)2][BArF4] are shown to be effective in solid-state molecular organometallic catalysis (SMOM-Cat) for the isomerization of 1-butene to a mixture of cis- and trans-2-butene at 298 K and 1 atm, and studies suggest that catalysis is likely dominated by surface-active species. [Rh(Cy2PCH2CH2PCy2)(η2η2-NBA)][BArF4] is also shown to catalyze the transfer dehydrogenation of butane to 2-butene at 298 K using ethene as the sacrificial acceptor

On the Role of Disks in the Formation of Stellar Systems: A Numerical Parameter Study of Rapid Accretion

We study rapidly accreting, gravitationally unstable disks with a series of global, three dimensional, numerical experiments using the code ORION. In this paper we conduct a numerical parameter study focused on protostellar disks, and show that one can predict disk behavior and the multiplicity of the accreting star system as a function of two dimensionless parameters which compare the disk's accretion rate to its sound speed and orbital period. Although gravitational instabilities become strong, we find that fragmentation into binary or multiple systems occurs only when material falls in several times more rapidly than the canonical isothermal limit. The disk-to-star accretion rate is proportional to the infall rate, and governed by gravitational torques generated by low-m spiral modes. We also confirm the existence of a maximum stable disk mass: disks that exceed ~50% of the total system mass are subject to fragmentation and the subsequent formation of binary companions.Comment: 16 pages, 12 figures, submitte