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PubMed2005

Models of general frequency-dependent selection and mating-interaction effects and the analysis of selection patterns in Drosophila inversion polymorphisms.

We investigate mechanisms of balancing selection by extending two deterministic models of selection in a one-locus two-allele genetic system to allow for frequency-dependent fitnesses. Specifically we extend models of constant selection to allow for general frequency-dependent fitness functions for sex-dependent viabilities and multiplicative fertilities, while non-multiplicative mating-dependent components remain constant. We compute protected polymorphism conditions that take the form of harmonic means involving both the frequency- and the mating-dependent parameters. This allows for a direct comparison of the equilibrium properties of the frequency-dependent models with those of the constant models and for an analysis of equilibrium of the general model of constant fertility. We then apply the theory to analyze the maintenance of inversion polymorphisms in Drosophila subobscura and D. pseudoobscura, for which data on empirical fitness component estimates are available in the literature. Regression on fitness estimates obtained at different starting frequencies enables us to implement explicit fitness functions in the models and therefore to perform complete studies of equilibrium and stability for particular sets of data. The results point to frequency dependence of fitness components as the main mechanism responsible for the maintenance of the inversion polymorphisms considered, particularly in relation to heterosis, although we also discuss the contribution of other selection mechanisms.

Animals↗
PubMed1981

[Digoxin-quinidine and digoxin-amiodarone interactions. Effects on blood levels of the cardioactive glycoside].

With ever increasing frequency potentially dangerous interactions are reported between Cardiac Glycosides and other drugs, particularly the antiarrhythmic one. The AA, carried out this work with the intent of studying the possible modifications produced by Q and A on the SDL. First of all the AA. retrospectively studied the SDL of patients treated with the associations Q-D and A-D and this SDL was compared with the SDL of patients treated with D alone. Then 10 subjects treated sequentially, at first with D alone and after with the Q-D (5 p.) and A-D (5 p.) association, were studied. The results obtained confirm the data of other AA. regarding the Q-D interaction; in fact, in the presence of this antiarrhythmic drug, the SDL increase significantly following the concomitant pharmacological effects of the Cardiac Glycosides. The SDL on the contrary seem not be influenced by the A-D association. The AA. then reviewed the literature about the mechanism of the Q-D interaction. The majority of the AA. agree outlining a reduction of the Volume of Distribution and of D Clearance, in consequence of the concomitant administration of Q, which would explain the high SDL obtained. In conclusion the AA. suggest, when the Q-D association is mandatory, a 50% reduction of the D maintenance dose and to check periodically the ECG and SDL.

Adult↗
PubMed2006

Reducing warfarin medication interactions: an interrupted time series evaluation.

BACKGROUND: Computerized decision support reduces medication errors in inpatients, but limited evidence supports its effectiveness in reducing the coprescribing of interacting medications, especially in the outpatient setting. The usefulness of academic detailing to enhance the effectiveness of medication interaction alerts also is uncertain. METHODS: This study used an interrupted time series design. In a health maintenance organization with an electronic medical record, we evaluated the effectiveness of electronic medical record alerts and group academic detailing to reduce the coprescribing of warfarin and interacting medications. Participants were 239 primary care providers at 15 primary care clinics and 9910 patients taking warfarin. All 15 clinics received electronic medical record alerts for the coprescription of warfarin and 5 interacting medications: acetaminophen, nonsteroidal anti-inflammatory medications, fluconazole, metronidazole, and sulfamethoxazole. Seven clinics were randomly assigned to receive group academic detailing. The primary outcome, the interacting prescription rate (ie, the number of coprescriptions of warfarin-interacting medications per 10 000 warfarin users per month), was analyzed with segmented regression models, controlling for preintervention trends. RESULTS: At baseline, nearly a third of patients had an interacting prescription. Coinciding with the alerts, there was an immediate and continued reduction in the warfarin-interacting medication prescription rate (from 3294.0 to 2804.2), resulting in a 14.9% relative reduction (95% confidence interval, -19.5 to -10.2) at 12 months. Group academic detailing did not enhance alert effectiveness. CONCLUSIONS: This study, using a strong and quasi-experimental design in ambulatory care, found that medication interaction alerts modestly reduced the frequency of coprescribing of interacting medications. Additional efforts will be required to further reduce rates of inappropriate prescribing of warfarin with interacting drugs.

Acetaminophen↗
PubMed2003

Interchannel interaction of optical solitons.

We study interaction between two solitons from different frequency channels propagating in an optical fiber. The interaction may be viewed as an inelastic collision, in which energy is lost to continuous radiation due to small but finite third order dispersion. We develop a perturbation theory with two small parameters: the third order dispersion coefficient d(3), and the reciprocal of the interchannel frequency difference, 1/beta. We find that amplitude of the leading contribution to radiation emitted during the collision is proportional to d(3)/beta(2). The source term for this radiation is of the form that would be generated by a variation in the second order dispersion coefficient. In addition, the only other effects up to the combined third order of the perturbation theory are phase changes and position shifts of the solitons. Solitons propagating in a given frequency channel interact via radiation emitted due to collisions with many solitons from other frequency channels. We show that this intrachannel interaction effect, induced by many interchannel collisions, is identical to the radiation mediated intrachannel interaction effect observed for solitons propagating under the influence of disorder in the second order dispersion coefficient.

Journal Article↗
PubMed2000

Frequency and clinical outcome of potentially harmful drug metabolic interactions in patients hospitalized on internal and pulmonary medicine wards: focus on warfarin and cisapride.

Drug metabolic interactions present potential risks in patient care, but their frequency and relative importance as a clinical problem remains unclear. To assess the frequency and clinical outcome of potentially harmful drug metabolic interactions in hospitalized patients, the authors performed a survey of the medication data of patients treated on internal and pulmonary medicine wards in a university hospital. The database was searched for concomitantly administered drug pairs that would, according to Hansten and Horn's drug interaction database, carry a high risk for a clinically harmful metabolic drug interaction. Coadministrations involving warfarin or cisapride were subjected to further analysis regarding clinical outcome. A total of 142 patients were exposed to 150 interactions with potentially harmful clinical outcome, resulting in a frequency of 0.9% (95% CI 0.7% to 1.0%). Inhibition of warfarin metabolism by metronidazole produced significant overanticoagulation as evidenced by elevated international normalized ratio values, whereas inducers (rifampicin and phenobarbital) of warfarin metabolism significantly reduced the efficacy of warfarin. One case of minor bleeding and one case of clavicular vein thrombosis were detected as possible consequences of disturbed anticoagulation. The coadministration of cisapride and erythromycin significantly prolonged the corrected QT (QTc) interval and was associated with clinical symptoms of cardiac arrhythmias. Coadministration of cisapride with fluconazole or miconazole was not associated with prolongation of the QTc interval or cardiac sequelae. Evaluations of patient materials are needed to assess the clinical relevance of metabolic drug interactions.

Adult↗
PubMed2002

Comparison of binaural auditory brainstem responses and the binaural difference potential evoked by chirps and clicks.

Rising chirps that compensate for the dispersion of the travelling wave on the basilar membrane evoke larger monaural brainstem responses than clicks. In order to test if a similar effect applies for the early processing stages of binaural information, monaurally and binaurally evoked auditory brainstem responses were recorded for clicks and chirps for levels from 10 to 60 dB nHL in steps of 10 dB. Ten thousand sweeps were collected for every stimulus condition from 10 normal hearing subjects. Wave V amplitudes are significantly larger for chirps than for clicks for all conditions. The amplitude of the binaural difference potential, DP1-DN1, is significantly larger for chirps at the levels 30 and 40 dB nHL. Both the binaurally evoked potential and the binaural difference potential exhibit steeper growth functions for chirps than for clicks for levels up to 40 dB nHL. For higher stimulation levels the chirp responses saturate approaching the click evoked amplitude. For both stimuli the latency of DP1 is shorter than the latency of the binaural wave V, which in turn is shorter than the latency of DN1. The amplitude ratio of the binaural difference potential to the binaural response is independent of stimulus level for clicks and chirps. A possible interpretation is that with click stimulation predominantly binaural interaction from high frequency regions is seen which is compatible with a processing by contralateral inhibitory and ipsilateral excitatory (IE) cells. Contributions from low frequencies are negligible since the responses from low frequencies are not synchronized for clicks. The improved synchronization at lower frequencies using chirp stimuli yields contributions from both low and high frequency neurons enlarging the amplitudes of the binaural responses as well as the binaural difference potential. Since the constant amplitude ratio of the binaural difference potential to the binaural response makes contralateral and ipsilateral excitatory interaction improbable, binaural interaction at low frequencies is presumably also of the IE type. Another conclusion of this study is that the chirp stimuli employed here are better suited for auditory brainstem responses and binaural difference potentials than click stimuli since they exhibit higher amplitudes and a better signal-to-noise ratio.

Acoustic Stimulation↗
PubMed2006

"Presemantic" cognition in semantic dementia: six deficits in search of an explanation.

On the basis of a theory about the role of semantic knowledge in the recognition and production of familiar words and objects, we predicted that patients with semantic dementia would reveal a specific pattern of impairment on six different tasks typically considered "pre-" or "non-" semantic: reading aloud, writing to dictation, inflecting verbs, lexical decision, object decision, and delayed copy drawing. The prediction was that all tasks would reveal a frequency-by-typicality interaction, with patients performing especially poorly on lower-frequency items with atypical structure (e.g., words with an atypical spelling-to-sound relationship; objects with an atypical feature for their class, such as the hump on a camel, etc). Of 84 critical observations (14 patients performing 6 tasks), this prediction was correct in 84/84 cases; and a single component in a factor analysis accounted for 87% of the variance across seven measures: each patient's degree of impairment on atypical items in the six experimental tasks and a separate composite score reflecting his or her degree of semantic impairment. Errors also consistently conformed to the predicted pattern for both expressive and receptive tasks, with responses reflecting residual knowledge about the typical surface structure of each domain. We argue that these results cannot be explained as associated but unrelated deficits but instead are a principled consequence of a primary semantic impairment.

Aged↗
PubMed2005

Psychophysically determined asymmetrical lifting capabilities for different frequencies and containers.

Ten young male participants were tested their psychophysically determined 4-h maximum acceptable weight of lifting (MAWL) of 90-degree asymmetric lifting for three lifting frequencies (1 lift/min, 2 lifts/min, 4 lifts/min) and three lifting containers (50 x 35 x 15 cm, 70 x 35 x 15 cm, 50 x 50 x 15 cm). The results showed that the MAWL decreased with increasing frequency and container width or length dimension, while the interaction effect of frequency and container on MAWL was not significant. The MAWL ranged from 13.7 kg to 18 kg for the nine (3 frequencies x 3 containers) lifting conditions. When averaged across the levels of the other independent variable, the MAWL decreased by 7.4% and 16.1% for 2 lifts/min and 4 lifts/min as compared with the MAWL of 1 lift/min, respectively, and decreased by 1.6% and 9.4% for 70 x 35 x 15 cm and 50 x 50 x 15 cm as compared with the MAWL of 50 x 35 x 15 cm, respectively. Additionally, the discrepancies between the MAWL data and the recommended weight limits derived from the revised NIOSH equation were discussed.

Adult↗
PubMed2005

Exploring the impact of plasticity-related recovery after brain damage in a connectionist model of single-word reading.

The effect of retraining a damaged connectionist model of single-word reading was investigated with the aim of establishing whether plasticity-related changes occurring during the recovery process can contribute to our understanding of the pattern of dissociations found in brain-damaged patients. In particular, we sought to reproduce the strong frequency x consistency interactions found in surface dyslexia. A replication of Plaut, McClelland, Seidenberg, and Patterson's (1996) model of word reading was damaged and then retrained, using a standard backpropagation algorithm. Immediately after damage, there was only a small frequency x consistency interaction. Retraining the damaged model crystallized out these small differences into a strong dissociation, very similar to the pattern found in surface dyslexic patients. What is more, the percentage of regularization errors, always high in surface dyslexics, increased greatly over the retraining period, moving from under 10% to over 80% in some simulations. These results suggest that the performance patterns of brain-damaged patients can owe as much to the substantial changes in the pattern of connectivity occurring during recovery as to the original premorbid structure. This finding is discussed in relation to the traditional cognitive neuropsychological assumptions of subtractivity and transparency.

Algorithms↗
PubMed1989

A comparison of frequencies between mouse T cells and B cells which are mutually interactive and specific to each other.

Repertoire sizes of T cells and B cells were estimated by frequency studies using mouse helper T cell clone D10G4.1 (D10 for short) and monoclonal antibodies raised against the antigen recognition structures on D10 cells. The soluble form of these antibodies was capable of activating D10 cells to proliferate in the presence of exogenous IL-1. Moreover, among the heterogeneous peripheral T cells, there is a population of cells which respond to those antibodies. Normal spleen B cells were non-clonally activated by LPS in limiting dilution cultures and the supernatant was tested for its activation capacity on D10 cells. Precursor frequencies of B cells which produce D10 activating antibodies were in the range of one in millions. The presence of D10 cells in the limiting dilution cultures increased this frequency by a factor of more than ten. For the estimation of frequencies of a given T cell clone which is activated by anti-D10 antibodies, normal spleen T cells were activated either by beads coupled monoclonal antibodies or by Con A followed by specific soluble antibodies in the limiting dilution cultures, and thereafter specific proliferation was assayed. A group of monoclonal anti-receptor antibodies gave rise to a single hit curve with relatively low frequency of one in 10(4) to 10(5). Another group of antibodies revealed in addition to the low frequency population, a higher frequency population of one in thousands. The data taken together suggest the frequencies of mutually interactive B and T cells are in the range of one in 10(4) to 10(5), while among T cells, there can be seen another population of cells of ten to a hundred fold higher frequency. Consequently, direct idiotype-antiidiotypic interactions between lymphocytes should occur only once in 10(8) to 10(10) cells in the normal unstimulated immune system. Thus, it is more likely that interactions will take place between cells of more degenerated specificities. The implications of these findings in favour of multiple levels of connection among T cells which reflect the multiple levels of affinity of the recognition complex of T cells are discussed.

Animals↗
PubMed2005

Contributions from lateral interaction mechanisms to the human ERG can be studied with a two-frequency method.

We present a two-frequency method to investigate lateral interaction components (liERGs) in the human electroretinogram. Adjacent half cycles of sinusoidal gratings were modulated sinusoidally with different temporal frequencies f1 and f2. The liERGs were defined by the Fourier components at the intermodulation frequencies /f1 - f2/ and f1 + f2 which indicate nonlinear interactions between the half cycles. Significant liERGs were found in all subjects with a monotonic increase of the liERG magnitude in the spatial frequency range from f(s)=0.07 to 2.4 cpd. When /f1 - f2/ was below 5 Hz, liERGs were masked by noise intrusions. In a control experiment we demonstrated that the liERGs were not evoked by stray light artifacts. The liERGs may help to further differentiate the responses that are evoked by patterned stimuli within the retina.

Adult↗
PubMedDate not supplied

Thalamo-cortical interactions modeled by weakly connected oscillators: could the brain use FM radio principles?

We consider all models of the thalamo-cortical system that satisfy the following two assumptions: (1) each cortical column is an autonomous oscillator; (2) connections between cortical columns and the thalamus are weak. Our goal is to deduce from these assumptions general principles of thalamo-cortical interactions that are independent of the equations describing the system. We find that the existence of synaptic connections between any two cortical columns does not guarantee that the columns interact: They interact only when there is a certain nearly resonant relation between their frequencies, which implies that the interactions are frequency modulated (FM). When the resonance relation holds, the cortical columns interact through phase modulations. Thus, communications between weakly connected cortical oscillators employ a principle similar to that in FM radio: The frequency of oscillation encodes the channel of communication, while the information is transmitted via phase modulations. If the thalamic input has an appropriate frequency, then it can dynamically link any two cortical columns, even those that have non-resonant frequencies and would otherwise be unlinked. Thus, by adjusting its temporal activity, the thalamus has control over information processing taking place in the cortex. Our results suggest that the mean firing rate (frequency) of periodically spiking neuron does not carry any information other than identifying a channel of communication. Information (i.e. neural code) is carried through modulations of interspike intervals.

Cerebral Cortex↗
PubMed1984

Interaction of physio-medical and psychosocial variables in age-related functional impairments.

Frequency of social interaction was studied in a group of twenty-five veterans who were temporary residents on a VA Nursing Home Care Unit. Serial learning tasks with a 4 sec. and 10 sec. exposure period and simple and choice reaction time tasks were also studied. At the conclusion of testing, attitudes toward aging, life satisfaction, and physical and mental impairment were assessed. "Social Activity" was positively correlated with each of four measures of serial learning, but was uncorrelated with either choice or simple reaction time. "Social Activity" was also correlated with more positive attitudes toward aging and with increased life satisfaction. However, certain aspects of physical and mental impairment were also related to task performance and level of social activity, suggesting that the psychosocial-behavior relationships observed may be partly mediated by a third factor, that is, the health status of the participant.

Aged↗
PubMed2004

Cortical convergence from different frequency domains in the cat primary auditory cortex.

Primary auditory cortex (AI) has a tonotopic map consisting of orderly isofrequency (IF) bands, and cortical connections are commonly supposed to link domains preferring similar characteristic frequencies (CFs) within AI and in auditory association cortex. The interaction of different frequency channels, however, has not fully been understood in terms of anatomical substrates. Here, by injecting two anterograde tracers in different frequency domains of cat AI, without overlap of the injection cores, we attempted to relate the anatomical mapping of cortical outputs to physiologically defined fields in the auditory cortex. Consistent with previous studies, patches of labeled axon terminals were oriented largely along the IF axis. In regions distant from the injection sites, however, terminal patches were divergent in distribution. This divergence resulted in a complex geometry of partial overlap of projections originating from the two injection sites. The relative extent of the overlap tended to vary depending on the distance between the two injection sites. Physiological mapping for tonotopy across auditory fields revealed that projectional overlap was characteristic of dorsal AI and the dorsoposterior field and, to a lesser extent, in the secondary auditory field. Considering the differences in frequency representation in different AI IF bands, the anatomical convergence of projections tuned to different CFs could contribute to the spectral integration of sound components. Furthermore, the different extent of convergence in the functionally distinct fields might reflect field-specific processing of acoustic signals.

Animals↗
PubMed2004

Alcohol drinking in middle age and subsequent risk of mild cognitive impairment and dementia in old age: a prospective population based study.

OBJECTIVE: To evaluate the relation between midlife alcohol consumption and mild cognitive impairment and dementia in old age, and the possible modification of this relation by apolipoprotein E. DESIGN: Prospective, population based study. SETTING: Populations of Kuopio and Joensuu, eastern Finland. PARTICIPANTS: Of 1464 men and women aged 65-79 years randomly selected from population based samples studied in 1972 or 1977, 1018 (70%) were re-examined in 1998 (after an average follow up of 23 years). MAIN OUTCOME MEASURES: Mild cognitive impairment and dementia in old age. RESULTS: Participants who drank no alcohol at midlife and those who drank alcohol frequently were both twice as likely to have mild cognitive impairment in old age as those participants who drank alcohol infrequently. The risk of dementia related to alcohol drinking was modified by the presence of the apolipoprotein e4 allele. The carriers of apolipoprotein e4 had an increased risk of dementia with increasing alcohol consumption: compared with non-carriers who never drank, the odds ratio for carriers who never drank was 0.6, for infrequent drinkers it was 2.3, and for frequent drinkers was 3.6 (the overall interaction term "drinking frequency(*)apolipoprotein e4" was significant (P = 0.04), as were the interactions "infrequent drinking(*)apolipoprotein e4" (P = 0.02) and "frequent drinking(*)apolipoprotein e4" (P = 0.03)). Non-carriers of apolipoprotein e4 had similar odds ratios for dementia irrespective of alcohol consumption. CONCLUSION: Alcohol drinking in middle age showed a U shaped relation with risk of mild cognitive impairment in old age. Risk of dementia increased with increasing alcohol consumption only in those individuals carrying the apolipoprotein e4 allele.

Aged↗
PubMedDate not supplied

Social support and the persistence of complaints in chronic fatigue syndrome.

BACKGROUND: Several studies suggested that the surroundings of chronic fatigue syndrome (CFS) patients are of importance in the persistence of complaints. Contrary to what was expected, participation in support groups has not led to clinical improvement. The purpose of the present study was to describe social support in CFS patients as compared with other fatigued and non-fatigued groups. Further, changes in social support and the influence of social support on the course of CFS over a period of more than 1 year were studied in patients with and without treatment. METHODS: Baseline data were assessed in 270 CFS patients, 150 disease-free breast cancer patients, 151 fatigued employees on sick-leave and 108 healthy subjects using the Social Support List and Significant Others Scale. CFS patients were followed in cognitive behaviour therapy (CBT), guided support groups and natural course at 8 and 14 months. RESULTS: CFS patients and fatigued employees reported more negative interactions and insufficiency of supporting interactions than cancer patients and healthy controls. No differences in frequency of supporting interactions were found. Negative interactions decreased significantly after treatment with CBT, but did not change in support groups or natural course. In the natural course, higher fatigue severity at 8 months was predicted by more negative interactions at baseline. CONCLUSIONS: In CFS patients and fatigued employees, social support is worse than in disease-free cancer patients and healthy controls. Lack of social support was identified as a new factor in the model of perpetuating factors of fatigue severity and functional impairment in CFS.

Adolescent↗
PubMed1979

Spatial frequency masking in human vision: binocular interactions.

Binocular contrast interactions in human vision were studied psychophysically. Thresholds were obtained for sinewave grating stimulation of the right eye in the presence of simultaneous masking gratings presented to the right eye (monocular masking) or left eye (dichoptic masking). In the first experiment, thresholds were measured at 0.25, 1.0, 4.0, and 16.0 cycle per degree (cpd) as a function of the contrast of masking gratings of identical frequency and phase. Thresholds rose nonmonotonically with masking contrast. At medium and high contrast levels, dichoptic masking was more effective in elevating contrast thresholds than monocular masking, and approached Weber's Law behavior. In the second experiment, spatial frequency tuning functions were obtained for test gratings at five spatial frequencies, by measuring threshold elevation as a function of the spatial frequency of constant-contrast masking gratings. At 1.0, 4.0, and 16.0 cpd, the tuning functions peaked at the test frequencies. The dichoptic tuning functions had a bandwidth of about 1 octave between half-maximum points, narrower than +/- 1 octave bandwidths of the monocular tuning functions. At 0.125 and 0.25 cpd, the tuning functions were broader and exhibited a shift in peak masking to frequencies above the test frequencies.

Adult↗