Automobile-dependency as a barrier to vision zero, evidence from the states in the USA.

With a traffic fatality rate of 10.6 per 100,000 as of 2013-more than triple that in the UK, the Netherlands, and Sweden-the United States has the worst traffic safety performance of all developed countries. Statewide variations are even more pronounced.

Progress towards zero, an international comparison: Improvements in traffic fatality from 1990 to 2010 for different age groups in the USA and 15 of its peers.

Introduction: In January 2015, the United States Department of Transportation (USDOT) announced that the official target of the federal government transportation safety policy was zero deaths. Having a better understanding of traffic fatality trends of various age cohorts-and to what extent the US is lagging other countries-is a crucial first step to identifying policies that may help the USDOT achieve its goal.

Method: In this paper we analyze fatality rates for different age cohorts in developed countries to better understand how road traffic fatality patterns vary across countries by age cohort.

Does street network design affect traffic safety?

Negative binomial regression models were used to assess the effect of street and street network characteristics on total crashes, severe injury crashes, and fatal crashes. Data from over 230,000 crashes taking place over 11 years in 24 California cities was analyzed at the U.S.

A Special Fiber Optic Sensor for Measuring Wheel Loads of Vehicles on Highways.

This paper presents results from an investigation on a special optical fiber as a load sensor for application in Weigh-in-Motion (WIM) systems to measure wheel loads of vehicles traveling at normal speed on highways. The fiber used has a unique design with two concentric light guiding regions of different effective optical path lengths, which has the potential to enable direct measurement of magnitudes as well as locations of forces acting at multiple points along a single fiber. The optical characteristic of the fiber for intended sensing purpose was first assessed by a simple fiber bending experiment and by correlating the bend radii with the output light signal intensities.

Neuroscience findings in AIDS: a review of research sponsored by the National Institute of Mental Health.

1. The human immunodeficiency virus (HIV-1) infects cells in both the immune system and the brain, but these effects are not independent. 2.

Minipump clorgyline administration and CSF amine metabolites in unrestrained monkeys.

The irreversible MAO-A inhibitor clorgyline was administered in doses of 0.5 mg/kg (N = 1), 1 mg/kg (N = 3), and 2 mg/kg (N = 1) to 5 young (age 5.5 to 23.

Plasma amine oxidase activities in Norrie disease patients with an X-chromosomal deletion affecting monoamine oxidase.

Two individuals with an X-chromosomal deletion were recently found to lack the genes encoding monoamine oxidase type A (MAO-A) and MAO-B. This abnormality was associated with almost total (90%) reductions in the oxidatively deaminated urinary metabolites of the MAO-A substrate, norepinephrine, and with marked (100-fold) increases in an MAO-B substrate, phenylethylamine, confirming systemic functional consequences of the genetic enzyme deficiency. However, urinary concentrations of the deaminated metabolites of dopamine and serotonin (5-HT) were essentially normal.

Intravenous physostigmine increases cerebrospinal fluid neuropeptide-Y.

The ability to measure directly central nervous system (CNS) neurotransmitter changes after an acute pharmacological challenge would be a useful clinical tool in psychiatric research. As one approach to this possibility, we attempted to measure cerebrospinal fluid (CSF) neuropeptide changes produced by an intravenous infusion of the indirect cholinergic agonist physostigmine. Six rhesus monkeys, with indwelling CSF catheters, had serial CSF samples removed before and after a 15 micrograms/kg physostigmine infusion.

Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the dog: effect of pargyline pretreatment.

Adult beagle dogs of either sex were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-HCl (2.5 mg/kg, i.v.

Effects of xylazine on cerebrospinal fluid catecholamines in the rhesus monkey.

The i.v. administration of xylazine, a potent, selective alpha 2-adrenergic receptor agonist, resulted in a 76% decrease in cerebrospinal fluid (CSF) norepinephrine in chair-adapted rhesus monkeys.

Effects of fenfluramine, m-chlorophenylpiperazine, and other serotonin-related agonists and antagonists on penile erections in nonhuman primates.

Fenfluramine, m-chlorophenylpiperazine (m-CPP), 1-phenylpiperazine, and the buspirone metabolite, 1-(2-pyrimidyl)piperazine given intravenously to adult rhesus monkeys regularly elicited penile erections. In contrast, serotonin (5-HT) agonists with 5-HT1A site specificity (8-OH-DPAT, buspirone) as well as trazodone, ritanserin, and metergoline were no different from saline in producing penile erections. Fenfluramine's effects were blocked by the 5-HT2 antagonists, ritanserin and metergoline, while m-CPP's effects were not blocked by the peripheral 5-HT antagonist, xylamidine, indicating that tumescence can be elicited by serotonergic agents which act at non-5-HT1A sites in the central nervous system.

Corticotropin-releasing factor: a marked circadian rhythm in primate cerebrospinal fluid peaks in the evening and is inversely related to the cortisol circadian rhythm.

Continuous sampling of cerebrospinal fluid (CSF) over 24-h periods in 10 rhesus monkeys revealed a 2-fold, highly reproducible circadian rhythm in CRF concentrations. Peak CRF values of 77.9 +/- 6.

Marked enhancement by clorgyline of nocturnal and daytime melatonin release in rhesus monkeys.

The type A monoamine oxidase (MAO)-inhibiting antidepressant clorgyline (1 mg/kg/24 days) administered to rhesus monkeys increased night-time cerebrospinal fluid (CSF) melatonin concentrations 3-fold and day-time maltonin values 5-fold. Other circadian parameters of melatonin release, including the peak time and duration of nocturnal melatonin elevation measured during continuous CSF collection periods of 90 min duration over 24-h cycles, were unaffected by clorgyline. While pinealocytes are thought to contain only MAO-B, treatment with the selective MAO-B inhibitor deprenyl (2 mg/kg/24 days) did not alter day or night-time melatonin concentrations.

Use of serotonergic agents in the clinical assessment of central serotonin function.

To assess the status of the brain serotonergic system in relation to ongoing behavior, agents with predominant actions on serotonin synthesis, release, uptake, and receptor mechanisms are being evaluated. Abnormalities in the neuroendocrine responses to tryptophan, 5-hydroxytryptophan, fenfluramine, and m-chlorophenylpiperazine are under exploration in depressed patients. These agents are also being used to assess postulated changes in serotonin metabolism and serotonin receptor adaptation during longer term treatment with antidepressant drugs, lithium, and other psychoactive agents.

Human plasma melatonin is elevated during treatment with the monoamine oxidase inhibitors clorgyline and tranylcypromine but not deprenyl.

Melatonin was measured in plasma collected between 8:00 and 8:30 a.m. from 27 depressed patients studied before and after 21- to 24-day treatment with three monoamine oxidase (MAO) inhibitors.

How antidepressants work: cautionary conclusions based on clinical and laboratory studies of the longer-term consequences of antidepressant drug treatment.

Time-dependent alterations in the functional activity of adrenergic and serotonergic neurotransmitter systems and, in particular, a frequently observed down-regulation of brain beta-adrenoceptors have been implicated in antidepressant drug effects. Current studies of catecholamine and serotonin neurotransmitter systems suggest that the net physiological output changes in neuroendocrine responses, blood pressure, sleep and motor activity which follow various antidepressant treatments in psychiatric patients, normal controls and different experimental animals are not indicative of a common response pattern to all therapeutically effective agents. Rather, antidepressant treatment effects differ according to many variables, including the pre-existing state of the organism (e.

Effects of antidepressants and other psychotropic drugs on melatonin release and pineal gland function.

Antidepressants and some other psychotropic drugs affect the synthesis and release of melatonin through several mechanisms. Monoamine oxidase (MAO)-inhibiting antidepressants increase pineal concentrations of the melatonin precursors, serotonin (5-HT) and N-acetyl serotonin (NAS), in rodents, and also increase pineal N-acetyl transferase activity as well as both daytime and nighttime plasma melatonin concentrations; they also elevate melatonin, 5-HT and NAS in the cerebrospinal fluid of non-human primates. In humans treated with the MAO-A selective inhibitor, clorgyline, or the nonselective inhibitor, tranylcypromine, increased plasma melatonin also occurs; in contrast, the MAO-B selective inhibitor, 1-deprenyl, does not affect plasma melatonin.

The effects of amiflamine on cerebrospinal fluid amine metabolites in the rhesus monkey.

Amiflamine, a drug reported to be a reversible inhibitor of monoamine oxidase type A (MAO-A) selective for serotonergic neurons in rodents, was administered to rhesus monkeys over a 12-fold dosage range (0.5-6 mg/kg). Amiflamine produced small, essentially equivalent reductions in cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA, 1-28%), 3-methoxy-4-hydroxyphenylglycol (MHPG, 4-26%), and homovanillic acid (HVA, 7-29%), suggesting that the effects of amiflamine are approximately equal on serotonin, norepinephrine and dopamine metabolism in nonhuman primates.

Brain and liver monoamine oxidase type A and type B activity in alcoholics and controls.

Monoamine oxidase activity in human postmortem brain and liver samples was measured in a group of patients with a prior history of alcoholism and compared to a control group with no prior history of alcoholism. Liver samples from patients with a prior history of alcoholism showed significantly lower monoamine oxidase activity with both phenylethylamine and serotonin as substrates. Postmortem brain samples, however, were not different in the two groups.

Rhesus monkey cerebrospinal fluid amine metabolite changes following treatment with the reversible monoamine oxidase type-A inhibitor cimoxatone.

The effects of cimoxatone, a reversible inhibitor of monoamine oxidase type A (MAO-A), on the deaminated metabolites of norepinephrine, dopamine, and serotonin were examined in continuously collected rhesus monkey cerebrospinal fluid (CSF). Cimoxatone, 0.5-8 mg/kg given PO, produced dose-proportionate reductions of 24-h mean CSF 3-methoxy, 4-hydroxy phenylglycol (MHPG) concentrations of 21%-52%.

New contributions from basic science to understanding the effects of monoamine oxidase inhibiting antidepressants.

Recent studies have provided almost conclusive evidence for the existence of the two separate MAO isozymes previously postulated to exist on the basis of indirect evidence. Important differences in the proportions and distribution of these two enzyme forms across species and in various tissues are responsible for some puzzling anomalies in earlier studies and contribute to differences in behavioral responses, blood pressure changes, and toxic responses to tyramine and other sympathomimetic agents. Substrate-selective, irreversible inhibitors, as well as several new classes of reversible MAO-A and MAO-B selective inhibitors, may provide a spectrum of clinical effects different from the nonselective irreversible MAO inhibitors.

Differential effects of clorgyline on catecholamine and indoleamine metabolites in the cerebrospinal fluid of rhesus monkeys.

The effects of acute and chronic administration of clorgyline, an irreversible inhibitor of monoamine oxidase type A (MAO-A), on the deaminated metabolites of norepinephrine, dopamine and serotonin were examined in rhesus monkey cerebrospinal fluid (CSF). Acute clorgyline treatment resulted in highly significant, dose-dependent reductions in 3-methoxy-4-hydroxyphenylglycol (MHPG) of 50% (1 mg/kg) and 68% (2 mg/kg) compared to pretreatment values. Chronic clorgyline administration (0.

Effect of clorgyline (a MAO type A inhibitor) on locomotor activity in the Syrian hamster.

Syrian hamsters in a lighting schedule of 14 h of light per day (LD 14:10) and housed in cages equipped with running wheels exhibited a clear onset of locomotor activity during the 1st h after lights off. Implantation of osmotic minipumps containing clorgyline (2 mg . kg-1 .