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PubMed2004

Anthropic selection for the Moon's mass.

This paper investigates whether anthropic selection explains the unusually large size of our Moon. It is shown that obliquity stability of the Earth is possible across a wide range of different starting conditions for the Earth-Moon system. However, the lunar mass and angular momentum from the actual Earth-Moon system are remarkable in that they very nearly produce an unstable obliquity. This may be because the particular properties of our Earth-Moon system simultaneously allow a stable obliquity and a slow rotation rate. A slow rotation rate may have been anthropically selected because it minimizes the equator-pole temperature difference, thus minimizing climatic fluctuations. The great merit of this idea is that it can be tested using extrasolar planet search programs planned for the near future. If correct, such anthropic selection predicts that most extrasolar planetary systems will have significantly larger perturbation frequencies than our own Solar System.

Biological Evolution↗
PubMedDate not supplied

Pharmacokinetics and pharmacodynamics of midazolam given via continuous intravenous infusion in intensive care units.

Critically ill patients often benefit from sedation to optimize their care and their ventilatory support. Ideally, incremental doses of a drug are administered to produce the desired level of sedation without toxicity or overdose. Because metabolism and elimination of drugs are often altered in critically ill patients, knowledge of the pharmacokinetics of sedative hypnotics is essential to ensure their appropriate selection and administration. Furthermore, the administration of sedatives via continuous infusion minimizes fluctuations in drug concentrations and permits more consistent control of the patient's agitation and anxiety. Physician preference and the patient's individual requirements and underlying diseases are the primary determinants for the selection of a given sedative. Benzodiazepines are the most commonly used sedatives in critical care. Midazolam is readily distinguished from other benzodiazepines because of its rapid onset and short duration of action, low incidence of thrombophlebitis and pain on injection, and minimal cardiovascular and respiratory effects. The physiochemical properties of midazolam allow for enhanced water solubility, which limits physicochemical incompatibilities. These properties make midazolam a valuable sedative that can be given via continuous intravenous infusion in the intensive care unit.

Animals↗
PubMed1983

Vitamin fluctuations in the blood of female baboons in relation to normal menstrual cycles, treatments with Lo-Ovral or Depo-Provera and a selected vitamin supplement.

Both endogenous and exogenous sex steriods may induce changes in plasma vitamin levels by altering availability, transport, binding, or use of vitamins. This study investigated some of those mechanisms by observing in a primate model (baboon), the blood levels of carotene, folate, vitamins A, B12, and C, and the status of vitamin B6, riboflavin, and thiamin. The latter three vitamins were studied by determining their relationship to asparate aminotransferase, glutathione reductase, and thiamin transketolase, respectively. The vitamin screen was obtained throughout normal menstrual cycles in 10 baboons and weekly for 55 wk in five baboons receiving Lo-Ovral and in four baboons receiving Provera. During the last 16 wk of hormonal treatment, all baboons received a vitamin supplement containing pyridoxine, riboflavin, and thiamin. Only carotene (p less than 0.0001), vitamin A (p less than 0.05), glutathione reductase (p less than 0.05), and thiamin transketolase (p less than 0.05) levels fluctuated significantly during normal menstrual cycles. Long-term treatment with Lo-Ovral and Provera resulted in numerous changes but there were very few differences between the two hormone treatments. Compared to control levels, vitamin C was elevated during treatment while all three enzyme activities were lowered. Vitamin supplementation raised asparate aminotransferase and glutathione reductase activity and the levels of folic acid, vitamin A, and carotene. This study demonstrates that interactions between hormones and vitamins and among vitamins themselves, are complex but it is likely that the treatments used here caused no physiologically significant vitamin alterations.

Animals↗
PubMed2005

A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study.

BACKGROUND: Rasagiline (n-propargyl-1[R]-aminoindan) mesylate is a novel irreversible selective monoamine oxidase type B inhibitor, previously demonstrated to improve symptoms in early Parkinson disease (PD). OBJECTIVE: To determine the safety, tolerability, and efficacy of rasagiline in levodopa-treated patients with PD and motor fluctuations. DESIGN: Multicenter, randomized, placebo-controlled, double-blind, parallel-group study. PATIENTS: Parkinson disease patients (N = 472) with at least 21/2 hours of daily "off" (poor motor function) time, despite optimized treatment with other anti-PD medications. INTERVENTIONS: Rasagiline, 1.0 or 0.5 mg/d, or matching placebo. MAIN OUTCOME MEASURES: Change from baseline in total daily off time measured by patients' home diaries during 26 weeks of treatment, percentage of patients completing 26 weeks of treatment, and adverse event frequency. RESULTS: During the treatment period, the mean adjusted total daily off time decreased from baseline by 1.85 hours (29%) in patients treated with 1.0 mg/d of rasagiline, 1.41 hours (23%) with 0.5 mg/d rasagiline, and 0.91 hour (15%) with placebo. Compared with placebo, patients treated with 1.0 mg/d rasagiline had 0.94 hour less off time per day, and patients treated with 0.5 mg/d rasagiline had 0.49 hour less off time per day. Prespecified secondary end points also improved during rasagiline treatment, including scores on an investigator-rated clinical global impression scale and the Unified Parkinson's Disease Rating Scale (activities of daily living in the off state and motor performance in the "on" state). Rasagiline was well tolerated. CONCLUSIONS: Rasagiline improves motor fluctuations and PD symptoms in levodopa-treated PD patients. In light of recently reported benefits in patients with early illness, rasagiline is a promising new treatment for PD.

Aged↗
PubMedDate not supplied

[Distortion products in Menière's disease].

Distortion Product Otoacoustic Emissions (DPOAEs) are elicited by simultaneous application of two tones to the ear canal. These emissions are a result of nonlinear mechanical characteristics of the cochlea at a specific point and have a precise mathematical relation with the frequencies of the two eliciting primary tones f1 and f2. This frequency-selective property of DPOAEs suggests that they should be regarded as useful monitor of localized cochlear function at any predetermined frequency. The present study was designed to investigate DPOAEs in patients with Menière's disease. DPOAEs were recorded before and after glycerol administration to verify if the fluctuation of the hearing threshold induced by this hyperosmotic agent causes selective changes in the activity of the outer hair cells. DPOAEs were present in patients in which the mean duration of the disease was shorter compared to those patients without measurable DPOAEs. An improvement of DPOAEs after glycerol intatte was observed in a half of our cases. The improvement of DPOAEs does not appear to be brought about by modifications of the auditory threshold induced by glycerol.

Audiometry↗
PubMed1992

Dopamine agonist treatment of fluctuating parkinsonism. D-2 (controlled-release MK-458) vs combined D-1 and D-2 (pergolide)

Adjunctive treatment with the very potent and selective dopamine D-2 agonist MK-458 (controlled-release formulation) improved the control of parkinsonism in patients with fluctuating responses to levodopa therapy (with carbidopa). We subsequently switched patients to adjunctive treatment with pergolide, a less potent D-2 agonist. Pergolide therapy controlled parkinsonism more effectively than controlled-release MK-458. Unlike MK-458, pergolide mesylate also has D-1 agonist properties, apparently accounting for its greater antiparkinsonism efficacy. Adjunctive treatment with controlled-release MK-458 elicited less choreiform dyskinesias than either pergolide adjunctive therapy or therapy with carbidopa-levodopa alone; this finding suggests that D-1 receptor stimulation contributes to the elicitation of medication-induced chorea. The highest doses of controlled-release MK-458 resulted in paradoxical freezing of gait in almost one third of patients. This finding suggests that gait freezing, common in untreated parkinsonism, can also be elicited by excessive D-2 stimulation.

Adult↗
PubMed1999

Selection of refractory and permissive strains of Aedes triseriatus (Diptera: Culicidae) for transovarial transmission of La Crosse virus.

The genetic basis of transovarial transmission of La Crosse virus in Aedes triseriatus (Say) was investigated through selection experiments on 2 mosquito strains. One strain was subject to selection for transovarial transmission refractoriness, the other for permissiveness to transovarial transmission. Response to selection for a low filial infection rate was rapid, decreasing from 18 to 3% in 3 generations. However, no response to selection for permissiveness was observed in the other strain; the average filial infection rates through 4 generations fluctuated between 25 and 40%. By contrast, the transovarial transmission rate in both strains showed a consistent response to selection in both directions. These patterns are consistent with a model in which transovarial transmission is controlled by a single genetic locus and permissiveness is conditioned by dominant alleles; whereas the filial infection rate is nongenetic and influenced by stochastic factors in the mosquito and virus.

Aedes↗
PubMed1991

The MMPI and premenstrual syndrome: profile fluctuations between best and worst times during the menstrual cycle.

The MMPI was administered during the patient-perceived best time of the menstrual cycle and during the patient-perceived worst time of the cycle in order to examine the stability of MMPI profile configurations. Subjects were 214 women who were referred to two metropolitan outpatient premenstrual syndrome (PMS) clinics for moderate to severe premenstrual complaints. This sample was selected from 1,849 intake files after screening by strict selection criteria for PMS. The results indicate that there are wide fluctuations in profile patterns between the best and worst times of the menstrual cycle for a large number of patients. Caution in using the MMPI is strongly advised.

Adult↗
PubMed2004

MoViES: molecular vibrations evaluation server for analysis of fluctuational dynamics of proteins and nucleic acids.

Analysis of vibrational motions and thermal fluctuational dynamics is a widely used approach for studying structural, dynamic and functional properties of proteins and nucleic acids. Development of a freely accessible web server for computation of vibrational and thermal fluctuational dynamics of biomolecules is thus useful for facilitating the relevant studies. We have developed a computer program for computing vibrational normal modes and thermal fluctuational properties of proteins and nucleic acids and applied it in several studies. In our program, vibrational normal modes are computed by using modified AMBER molecular mechanics force fields, and thermal fluctuational properties are computed by means of a self-consistent harmonic approximation method. A web version of our program, MoViES (Molecular Vibrations Evaluation Server), was set up to facilitate the use of our program to study vibrational dynamics of proteins and nucleic acids. This software was tested on selected proteins, which show that the computed normal modes and thermal fluctuational bond disruption probabilities are consistent with experimental findings and other normal mode computations. MoViES can be accessed at http://ang.cz3.nus.edu.sg/cgi-bin/prog/norm.pl.

Computational Biology↗
PubMed2005

Fluctuating energy level Landau-Teller theory: application to the vibrational energy relaxation of liquid methanol.

State-to-state vibrational energy relaxation (VER) rates of the OH-stretch fundamental to select vibrational modes of liquid methanol are presented. The rates are calculated via a modified, fluctuating Landau-Teller (FLT) theory approach, which allow for dynamical vibrational energy level shifts. These rates are then compared to previously published results from Gulmen and Sibert [J. Phys. Chem. A 2004, 108, 2389] for the traditional Landau-Teller (LT) method as well as results calculated through time-dependent perturbation theory (TD), which naturally allow for the fluctuation. For the first time, this method is applied to a polyatomic molecular system, and the FLT theory greatly reduces the discrepancy between the LT and TD results or, at a minimum, is comparable to the LT approach with very little additional computational cost.

Journal Article↗
PubMed1990

Kainate activated single channel currents as revealed by domoic acid.

We have studied the properties of kainic acid receptor-activated channels using domoic acid as an agonist. Similarities of the electrophysiological, pharmacological and noise properties of domoic acid and kainic acid-evoked currents confirm that domoate is a potent and specific agonist of the kainate receptor. Single-channel properties of domoic acid-evoked currents were directly determined from outside-out membrane patches for the first time, and results were compared with those obtained by fluctuation analysis of macroscopic currents. Small conductance cationic-selective channels of approximately 4 pS and a mean open time of 2 to 3 ms were detected using both methods.

Animals↗
PubMed1986

Chloride channels activated by hyperpolarization in Aplysia neurones.

The outside-out configuration of the patch-clamp technique was used in order to characterize the elementary events underlying the previously described hyperpolarization-activated Cl current of Aplysia neurones. A few membrane patches bathed with K-free internal and external solutions showed channels characterized by long duration (up to several seconds) bursts of activity which were clearly activated by hyperpolarization. I-V curves of elementary current obtained for three different values of the Cl equilibrium potential show that these channels are selective for Cl ions. During the bursts, the current fluctuates between three levels: the resting (closed) level, a level of maximum conductance (10-15 pS) and a half-conductance level. This behaviour is similar to that of the Cl channels extracted from Torpedo electroplaques.

Animals↗
PubMed1992

A model of ion channel kinetics based on deterministic, chaotic motion in a potential with two local minima.

Models of the gating of ion channels have usually assumed that the switching between the open and closed states is a random process without a mechanistic basis. We explored the properties of a deterministic model of channel gating based on a chaotic dynamic system. The channel is modeled as a nonlinear oscillator, that has a potential function with two minima, which correspond to the stable open and closed states, and is driven by a periodic driving force. The properties of the model are like some properties of single channel data and unlike other properties. The model is like the data in that: the current switches between two well-defined states, this switching is nonperiodic, and there are subconductance states. These subconductance states are subharmonic resonances, due to the nonlinearities in the equation of the model, rather than stable conformational states due to local minima in the potential energy. The model is not like the data in that the current fluctuates too much within in each state and there are sometimes periodic fluctuations within a state. At the present time, the selection of the most appropriate channel model (Markov, chaotic, or other) is not possible, and in addition to chaotic models, other nonlinear models may be suitable.

Ion Channels↗
PubMed2006

Women with asthma: a review of potential variables and preferred medical management.

OBJECTIVES: To summarize the potential variables that contribute to the increased risk of asthma in women, outline therapeutic strategies that address these variables, and review current treatment recommendations for both pregnant and nonpregnant women with asthma. DATA SOURCES: Literature searches (MEDLINE and cross-references) were performed using the keywords asthma and women in combination with the terms compliance, depression, emergency department, hormones, menstruation, mortality, National Asthma Education and Prevention Program, osteoporosis, pregnancy, prevalence, smoking, and treatment. Searches were limited to human studies with data published before 2005. STUDY SELECTION: The author selected relevant articles for inclusion in this review. RESULTS: Fluctuations in sex hormones, menstruation, pregnancy, obesity, depression, medication nonadherence, and smoking may contribute to increased asthma symptoms or severity in women. Asthma control may be improved if physicians address conditions and behaviors associated with asthma variability and severity in women. Notably, asthma must be managed aggressively in pregnant women, because uncontrolled asthma can lead to perinatal complications. Asthma treatment in women is optimized through patient and physician adherence to national guideline recommendations, including provision of patient education and asthma action plans. CONCLUSIONS: Multiple variables throughout the female life cycle may influence asthma control. Successful asthma management requires an ongoing partnership between the patient and her physician to address physiologic (eg, sex hormones, pregnancy, obesity, depression) and nonphysiologic (eg, smoking, medication nonadherence) factors that may contribute to decreased asthma control.

Adult↗
PubMed1996

Economic swings and demographic changes in the history of Latin America.

In this paper we study the effects of short-term fluctuations in indicators of economic well-being on selected demographic response such as births, marriages and deaths at age intervals in eleven Latin American countries between 1910 and 1990. We use conventional distributed lag models to assess the magnitude and direction of effects and test a variety of hypotheses some of which have been posed to hold in Western Europe and others that are more specific and tailored to the Latin American context. We also compare the magnitude and direction of effects obtained among these countries with those obtained for pre-industrial Europe and uncover the existence of broadly similar patterns.

Demography↗
PubMed1976

Multilocus behavior in random environments. I. Random Levene models.

In this paper the consequences of natural selection acting on several loci simultaneously in a spatially fluctuating environment are described. The fitnesses of the genotypes are assumed to be additive both within and between loci. The environment is assumed to be made up of a very large (effectively infinite) number of patches in which fitnesses are assigned at random. The resulting deterministic model is called a Random Levene Model and its properties are approximate by a system of differential equations. The main equilibrium properites are that (1) the linkage disequilibrium is zero and (2) the correlations in fitness between alleles at different loci are the principle determinants of the dynamic inter-locus interactions. Although there is no epistasis as conventionally defined, the equilibrium state at the two loci are highly interdependent, the governing principle being that two alleles at different loci whose fitness are negatively correlated across environments have a higher overall fitness due to the reduction in their variance in fitness through the negative correlation. When a large number of loci are considered, they naturally fall into correlation groupings which lead to an enhanced likelihood for polymorphism over that predicted by single-locus theory.

Biological Evolution↗
PubMed1983

Physiological variation of mouse haemoglobins.

Polymorphism at Hbb (haemoglobin beta-chain) is widespread in natural populations of the house mouse, Mus musculus, and appears to be maintained by natural selection. This report is an attempt to correlate genotypic fluctuations at Hbb with a most important physiological attribute of haemoglobin, its oxygen carrying capacity. Oxygen affinity has been studied and P50 values have been measured in 12 inbred strains as well as wild-caught mice from Skokholm island. The mean P50 of each inbred strain is a constant characteristic, although there is high within-strain variation and the oxygen affinity of the blood of an individual can fluctuate considerably from week to week. The causes of this variation remain obscure but neither within-strain nor between-strain differences are correlated with known modulators of oxygen binding. In general, the blood of mice of inbred strains as well as wild-caught mice that are homozygous for Hbbd tends to have a higher oxygen affinity than that from comparable animals homozygous for Hbbs, but it seems likely that the oxygen dissociation properties of haemoglobin are not the only ones important in determining differential survival of a particular Hbb type under varying environmental stress.

Animals↗
PubMed2000

Non-random fitness variation in two populations of Darwin's finches.

Darwinian fitness of an individual is measured by the number of recruits it contributes to the next generation. We studied variation in fitness among members of three cohorts of two species of Darwin's finches living on the Galipagos island of Daphne Major: the medium ground finch (Geospiza fortis) and cactus finch (Geospiza scandens). Individuals of both species live for up to 16 years. Variation in fitness was neither random nor heritable. Non-randomness arises as a result of a few individuals living for an exceptionally long time and breeding many times. For each cohort, the number of recruits per breeder is strongly predicted by the number of fledglings per breeder. In turn, the number of fledglings is strongly predicted by longevity of the breeder. These results suggest that the most important determinant of fitness is the ability of an individual to survive to breed in many years. Morphological traits affect this ability. Although morphological traits are heritable they do not change unidirectionally because they are selected in opposite directions, and in different combinations, under fluctuating environmental conditions. Non-random fitness variation in fluctuating populations implies much smaller genetically effective sizes than breeding population sizes.

Age Factors↗