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PubMed2000

Spontaneous activity in the statoacoustic ganglion of the chicken embryo.

Statoacoustic ganglion cells in the mature bird include neurons that are responsive to sound (auditory) and those that are not (nonauditory). Those that are nonauditory have been shown to innervate an otolith organ, the macula lagena, whereas auditory neurons innervate the basilar papilla. In the present study, single-unit recordings of statoacoustic ganglion cells were made in embryonic (E19, mean = 19.2 days of incubation) and hatchling (P6-P14, mean = 8.6 days posthatch) chickens. Spontaneous activity from the two age groups was compared with developmental changes. Activity was evaluated for 47 auditory, 11 nonauditory, and 6 undefined eighth nerve neurons in embryos and 29 auditory, 26 nonauditory, and 1 undefined neurons in hatchlings. For auditory neurons, spontaneous activity displayed an irregular pattern [discharge interval coefficient of variation (CV) was >0.5, mean CV for embryos was 1.46 +/- 0.58 and for hatchlings was 1.02 +/- 0.25; means +/- SD]. Embryonic discharge rates ranged from 0.05 to 97.6 spikes per second (sp/s) for all neurons (mean 18.6 +/- 16.9 sp/s). Hatchling spontaneous rates ranged from 1.2 to 185.2 sp/s (mean 66.5 +/- 39.6 sp/s). Discharge rates were significantly higher for hatchlings (P < 0.001). Many embryonic auditory neurons displayed long silent periods between irregular bursts of neural activity, a feature not seen posthatch. All regular bursting discharge patterns were correlated with heart rate in both embryos and hatchlings. Preferred intervals were visible in the time interval histograms (TIHs) of only one embryonic neuron in contrast to 55% of the neurons in posthatch animals. Generally, the embryonic auditory TIH displayed a modified quasi-Poisson distribution. Nonauditory units generally displayed regular (CV <0.5) or irregular (CV >0.5) activity and Gaussian and modified-Gaussian TIHs. Long silent periods or bursting patterns were not a characteristic of embryonic nonauditory neurons. CV varied systematically as a function of discharge rate in nonauditory but not auditory primary afferents. Minimum spike intervals (dead time) and interval modes for auditory neurons were longer in embryos (dead time: embryos 2.88 +/- 6.85 ms; hatchlings 1.50 +/- 1.76 ms; modal intervals: embryo 10.09 +/- 22.50 ms, hatchling 3.54 +/- 3.29 ms). The results show that significant developmental changes occur in spontaneous activity between E19 and posthatch. It is likely that both presynaptic and postsynaptic changes in the neuroepithelium contribute to maturational refinements during this period of development.

Acoustic Stimulation↗
PubMedDate not supplied

[Time trends in fatal traumatic occupational injuries in Spain [1992-2002]].

OBJECTIVE: To describe time trends in fatal traumatic occupational injuries by economic activity, type of contract, age, and gender between 1992 and 2002 in Spain. METHODS: The number of fatal traumatic occupational injuries occurring during the study period in salaried workers was 8,510. The annual percentage of change in fatal occupational injury rates was calculated by economic activity, type of employment, age group, and gender assuming a Poisson distribution. The incidence in 2002 was standardized by economic activity to adjust for the potential effect of changes in the labor market from 1992. Economic activities were regrouped according to their percentages of change in employees during the study period. RESULTS: The incidence of fatal traumatic injuries decreased by an annual percentage of -4.3% (95% CI, -5.3 to -3.4%) from a rate of 9.8 per 100,000 in 1992 to 6.1 in 2002, representing an overall reduction of 38% (relative risk = 0.62), particularly in expanding employment industries (-4.4%), women (-7.6%) and permanent employment (-4.3%). In 2002 the incidence was 8.5 after adjusting by economic activity in 1992 (adjusted relative risk = 0.87). CONCLUSIONS: The decreasing trend observed in fatal occupational injuries is similar to that observed in other developed countries. At least two thirds of this decrease can be explained by changes in productive structures. The results indicate the areas in which preventive activities should be concentrated.

Accidents, Occupational↗
PubMed2003

Frequency of X-linked ichthyosis in coastal southern Italy: a study on a representative sample of a young male population.

BACKGROUND: No reports on the frequency of X-linked ichthyosis (XLI) in the Italian general population and few surveys on the frequency of XLI in large communities in the world are available. OBJECTIVE: The aim of this study was the assessment of the frequency of XLI in a large representative sample of the Italian male population. SUBJECTS AND METHODS: This study involved young men who enlisted as conscripts in the Italian Navy from January 1998 through February 2002, examined, prior to enlistment, at the Draft Council's Medical Unit of the Italian Navy in Taranto, Italy, to evaluate their psychophysical fitness. All the patients with an ichthyosiform condition were referred to the Department of Dermatology of the Navy Hospital, underwent a thorough dermatological examination and completed a questionnaire regarding their personal and familial history. Pertinent results of the other clinical investigations were recorded and the final diagnosis was formulated on the basis of all these data. RESULTS: From January 1998 through February 2002, of 75,653 young men examined, 15 cases of XLI were diagnosed, with a frequency of 1:5,043 or 1.98 per 10,000 (95% confidence interval based on the Poisson distribution 1.01-2.90). Four out of 15 cases (26.6%) showed corneal opacities. No other significant associated pathological change was observed. CONCLUSIONS: As this study is a survey involving a large male sample, homogeneous with reference to age, race and country of origin (southern Italy), the frequency of XLI could be estimated at about 1.98 per 10,000 males. These data are roughly in agreement with estimates from other European surveys.

Adolescent↗
PubMed1988

Analysis of the 'epidemic' of multiple sclerosis in the Faroe Islands. II. Biostatistical aspects.

A series of biostatistical tests were applied to the data upon which the Faroe epidemic hypothesis was constructed. Temporal, cluster analysis using three commonly applied methods were unsuitable because of the very small size of the sample (32 cases of MS). Methods to detect non-random clusters of disease identified a cluster of 16 cases with date of onset between 1941-1950 (p less than 0.05). However, when 1 questionable case of MS was excluded, the resulting cluster did not support the epidemic hypothesis. The overlapping 95% confidence limits of 5- and 10-year based incidence rates of MS, by date of onset (Poisson distribution) argues against the presence of an epidemic. Analysis of the exposure data, i.e. contacts between the Faroese and the British troops, yielded only borderline statistical significance but changing a single case of MS from the exposed to the unexposed category failed to support the exposure theory. All calculations were also carried out using the probable date of acquisition of the disease, between the ages of 5 and 14 years; these also failed to substantiate the hypotheses of epidemic and transmissibility. Since the validity of statistical analysis to test for the presence of epidemics with small sample sizes is not well established, the lack of concordance between the results of the various approaches leads to the conclusion that there was no epidemic of MS in the Faroes.

Adolescent↗
PubMed1993

Prevalence of human immunodeficiency virus, hepatitis B virus and hepatitis C virus among dialysis patients. The Italian Multicentric Study on Nosocomial and Occupational Risk of Blood-Borne Infections in Dialysis.

In April 1991, a cross-sectional study of HIV, HBV and HCV markers among dialysis patients was carried out in 19 Italian units in order to evaluate the spread of these bloodborne infections among patients and to evaluate the potential risk for staff who care for them. A total of 2,180 patients were eligible and all consented to be tested. Of the 1,347 patients who had not been given hepatitis B vaccine, 67.9% had at least one marker of HBV infection; of these 9.2% were HBsAg carriers; conversely, the rates were 7.6 and 0.4%, respectively, among the 833 vaccinated patients. Antibodies against HCV were found in 501 patients (23%) by EIA C100-3; of these, 270 were tested by RIBA-100: 246 (91%) were reactive and 11 (4.1%) indeterminate. Five patients resulted anti-HIV positive [0.22%, 95% CI (Poisson distribution): 0.07-0.53] by EIA and Western blot techniques. Length of time on dialysis seems to correlate with higher prevalence of HBV and HCV infection markers, but (not) HIV. Overall, 608 (28%) patients were a potential source of infections for other patients and staff. This emphasizes the need for stricter adherence to infection control, barrier precautions and preventive behaviours with all patients.

Adolescent↗
PubMedDate not supplied

Endothelial transport of anionized and cationized ferritin in the rabbit thoracic aorta and vasa vasorum.

Transport of anionized ferritins (AF,pl = 3.8-4.2), weakly cationized ferritins (WCF, pI = 7.8-8.1) and cationized ferritins (CF, pI greater than 9.0) was investigated in the rabbit aorta and vasa vasorum. After a 2-minute in situ perfusion, all ferritin species entered luminal vesicles and bound to the luminal endothelial membrane with a high surface density at vesicle necks and regions of cell overlap. In comparison to the aorta, the vasa vasorum had a higher surface density for AF, lower surface densities for CF and WCF, and fewer vesicles containing CF, WCF, or AF. In both types of vessels, vesicle loading of all ferritin species did not agree with a Poisson distribution. After perfusion times of up to 30 minutes, no abluminal vesicles or vasa vasorum endothelium contained CF or WCF; a few abluminal vesicles near cell borders contained AF. In the vasa vasorum, CF and AF entered the subendothelium via occasional fenestrae; AF, but not CF, also permeated the adventitia. Our findings indicate that: 1) binding sites for oppositely charged particles coexist in the same microdomains; 2) the glycocalyces of the vasa vasorum and aorta differ in their relative affinities for oppositely charged particles; 3) vesicular labeling with ferritin is not solely diffusive; and 4) vesicles do not traverse the aortic endothelium under these experimental conditions.

Animals↗
PubMed2000

Multidimensional encoding strategy of spiking neurons.

Neural responses in sensory systems are typically triggered by a multitude of stimulus features. Using information theory, we study the encoding accuracy of a population of stochastically spiking neurons characterized by different tuning widths for the different features. The optimal encoding strategy for representing one feature most accurately consists of narrow tuning in the dimension to be encoded, to increase the single-neuron Fisher information, and broad tuning in all other dimensions, to increase the number of active neurons. Extremely narrow tuning without sufficient receptive field overlap will severely worsen the coding. This implies the existence of an optimal tuning width for the feature to be encoded. Empirically, only a subset of all stimulus features will normally be accessible. In this case, relative encoding errors can be calculated that yield a criterion for the function of a neural population based on the measured tuning curves.

Action Potentials↗
PubMed2005

Synaptic shot noise and conductance fluctuations affect the membrane voltage with equal significance.

The subthreshold membrane voltage of a neuron in active cortical tissue is a fluctuating quantity with a distribution that reflects the firing statistics of the presynaptic population. It was recently found that conductance-based synaptic drive can lead to distributions with a significant skew. Here it is demonstrated that the underlying shot noise caused by Poissonian spike arrival also skews the membrane distribution, but in the opposite sense. Using a perturbative method, we analyze the effects of shot noise on the distribution of synaptic conductances and calculate the consequent voltage distribution. To first order in the perturbation theory, the voltage distribution is a gaussian modulated by a prefactor that captures the skew. The gaussian component is identical to distributions derived using current-based models with an effective membrane time constant. The well-known effective-time-constant approximation can therefore be identified as the leading-order solution to the full conductance-based model. The higher-order modulatory prefactor containing the skew comprises terms due to both shot noise and conductance fluctuations. The diffusion approximation misses these shot-noise effects implying that analytical approaches such as the Fokker-Planck equation or simulation with filtered white noise cannot be used to improve on the gaussian approximation. It is further demonstrated that quantities used for fitting theory to experiment, such as the voltage mean and variance, are robust against these non-Gaussian effects. The effective-time-constant approximation is therefore relevant to experiment and provides a simple analytic base on which other pertinent biological details may be added.

Action Potentials↗
PubMedDate not supplied

The advantage of factorial mating under selection is uncovered by deterministically predicted rates of inbreeding.

Rates of inbreeding (DeltaF) in selected populations were predicted using the framework of long-term genetic contributions and validated against stochastic simulations. Deterministic predictions decomposed DeltaF into four components due to: finite population size, directional selection, covariance of genetic contribution of mates, and deviation of variance of family size from that expected from a Poisson distribution. Factorial (FM) and hierarchical (HM) mating systems were compared under mass and sib-index selection. Prediction errors were in most cases for DeltaF less than 10% and for rate of gain less than 5%. DelatF was higher with index than mass selection. DeltaF was lower with FM than HM in all cases except random selection. FM reduced the variance of the average breeding value of the mates of an individual. This reduced the impact of the covariance of contributions of mates on DeltaF. Thus, contributions of mates were less correlated with FM than HM, causing smaller deviations of converged contributions from the optimum contributions. With index selection, FM also caused a smaller variance of number of offspring selected from each parent. This reduced variance of family size reduced DeltaF further. FM increases the flexibility in breeding schemes for achieving the optimum genetic contributions.

Animals↗
PubMed2006

Thick blood film examination for Plasmodium falciparum malaria has reduced sensitivity and underestimates parasite density.

BACKGROUND: Thick blood films are routinely used to diagnose Plasmodium falciparum malaria. Here, they were used to diagnose volunteers exposed to experimental malaria challenge. METHODS: The frequency with which blood films were positive at given parasite densities measured by PCR were analysed. The poisson distribution was used to calculate the theoretical likelihood of diagnosis. Further in vitro studies used serial dilutions to prepare thick films from malaria cultures at known parasitaemia. RESULTS: Even in expert hands, thick blood films were considerably less sensitive than might have been expected from the parasite numbers measured by quantitative PCR. In vitro work showed that thick films prepared from malaria cultures at known parasitaemia consistently underestimated parasite densities. CONCLUSION: It appears large numbers of parasites are lost during staining. This limits their sensitivity, and leads to erroneous estimates of parasite density.

Animals↗
PubMed2007

Methods for peptide identification by spectral comparison.

BACKGROUND: Tandem mass spectrometry followed by database search is currently the predominant technology for peptide sequencing in shotgun proteomics experiments. Most methods compare experimentally observed spectra to the theoretical spectra predicted from the sequences in protein databases. There is a growing interest, however, in comparing unknown experimental spectra to a library of previously identified spectra. This approach has the advantage of taking into account instrument-dependent factors and peptide-specific differences in fragmentation probabilities. It is also computationally more efficient for high-throughput proteomics studies. RESULTS: This paper investigates computational issues related to this spectral comparison approach. Different methods have been empirically evaluated over several large sets of spectra. First, we illustrate that the peak intensities follow a Poisson distribution. This implies that applying a square root transform will optimally stabilize the peak intensity variance. Our results show that the square root did indeed outperform other transforms, resulting in improved accuracy of spectral matching. Second, different measures of spectral similarity were compared, and the results illustrated that the correlation coefficient was most robust. Finally, we examine how to assemble multiple spectra associated with the same peptide to generate a synthetic reference spectrum. Ensemble averaging is shown to provide the best combination of accuracy and efficiency. CONCLUSION: Our results demonstrate that when combined, these methods can boost the sensitivity and specificity of spectral comparison. Therefore they are capable of enhancing and complementing existing tools for consistent and accurate peptide identification.

Journal Article↗
PubMed2005

The incidence of deep and lobar intracerebral hemorrhage in whites, blacks, and Hispanics.

BACKGROUND: Black and Hispanic Americans have a greater risk of primary intracerebral hemorrhage (ICH) than whites. Deep ICH is most often associated with hypertension, while lobar ICH is associated with cerebral amyloid angiopathy. The authors conducted a population-based incidence study to directly compare the incidence of deep vs lobar ICH in all three race-ethnic groups. METHODS: The authors used an active hospital and community surveillance program and autopsy reports to identify incident ICH cases among white, black, and Caribbean Hispanic adults in Northern Manhattan between July 1993 and June 1997. Incidence rates were adjusted for age and sex to the 1990 US Census. CIs for risk ratios (RR) were calculated with Byar's chi2 approximation of the Poisson distribution. RESULTS: The authors identified 155 cases of ICH for an annual incidence of 30.9/100,000 (26.7 to 35.0). Men had a higher risk of ICH than women (RR 1.5, 95% CI 1.2 to 1.8), driven entirely by the incidence of deep ICH (RR 1.8) rather than lobar ICH (RR 1.0). Compared with whites, RR for blacks was all ICH 3.8 (2.2 to 8.9), deep 4.8 (2.3 to 21.1), lobar 2.8 (1.2 to 14.4); RR for Hispanics was all 2.6 (1.4 to 6.1), deep 3.7 (1.7 to 16.5), lobar 1.4 (0.4 to 7.4). CONCLUSIONS: ICH is a heterogeneous disease with deep and lobar subtypes distinguishable on an epidemiologic basis. The different patterns of these two subtypes in our race-ethnically diverse population lend credence to the notion that ICH should no longer be treated as a single entity.

Adult↗
PubMed1997

Analysis of relative biological effectiveness of high energy heavy ions in comparison to experimental data.

We report that the relative biological effectiveness (RBE) of accelerated heavy ions for inactivation of cells can be analyzed by using the quadratic dependence on the linear energy transfer (LET) of the cellular effect. For high-LET radiation in low-dose regions, the inactivation cross section (sigma) can be approximately expressed as sigma max [1-exp[-k.(LET/Li)2]; here, k is the number of heavy-ions traversed in a cell nucleus and Li is a geometrical parameter related to the DNA structure, which depends on cell type. This original expression was first presented by Powers et al [Int. J. Radiat. Biol. 14 (1968)]. Using this expression and the Poisson distribution for the stochastic property of particle hitting, the mortality of cell populations was calculated. The numerical results were compared to the RBE values recently obtained with Chinese hamster V79 cells, and an Lt value of 152 keV/micron was found to give the best fit. At LETs of between 30 and 500 keV/micron, the D10 values (10% survival dose) agreed with the experimental data within an error range of -15%-(+8%).

Animals↗
PubMed1979

Statistical analyses of the relative risk.

Let P1 be the probability of a disease in one population and P2 be the probability of a disease in a second population. The ratio of these quantities, R = P1/P2, is termed the relative risk. We consider first the analyses of the relative risk from retrospective studies. The relation between the relative risk and the odds ratio (or cross-product ratio) is developed. The odds ratio can be considered a parameter of an exponential model possessing sufficient statistics. This permits the development of exact significance tests and confidence intervals in the conditional space. Unconditional tests and intervals are also considered briefly. The consequences of misclassification errors and ignoring matching or stratifying are also considered. The various methods are extended to combination of results over the strata. Examples of case-control studies testing the association between HL-A frequencies and cancer illustrate the techniques. The parallel analyses of prospective studies are given. If P1 and P2 are small with large samples sizes the appropriate model is a Poisson distribution. This yields a exponential model with sufficient statistics. Exact conditional tests and confidence intervals can then be developed. Here we consider the case where two populations are compared adjusting for sex differences as well as for the strata (or covariate) differences such as age. The methods are applied to two examples: (1) testing in the two sexes the ratio of relative risks of skin cancer in people living in different latitudes, and (2) testing over time the ratio of the relative risks of cancer in two cities, one of which fluoridated its drinking water and one which did not.

Age Factors↗
PubMed1986

Comparison of the tumorigenic response of SENCAR and C57BL/6 mice to benzo(a)pyrene and the inter-experimental variability over a three-year period.

SENCAR and C57BL/6 mice were compared for their ability to produce tumors after benzo(a)pyrene [B(a)P] initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. SENCAR mice initiated with 101 micrograms/mouse B(a)P and promoted with TPA (2 micrograms/mouse, twice weekly) produced large numbers of papillomas, whereas C57BL/6 mice produced none after 26 weeks of promotion. Continued treatment of the B(a)P-initiated C57BL/6 mice with TPA up to 52 weeks did not induce any papillomas nor did higher doses of B(a)P. Application of increased doses of TPA (10 micrograms/mouse, twice weekly) to B(a)P-initiated C57BL/6 mice (404 micrograms/mouse) for 50 weeks produced few papillomas. Substantial papilloma formation in C57BL/6 mice was observed after weekly treatment with B(a)P (101 micrograms/mouse), with maximal production occurring at weeks 39 to 41 of treatment. In contrast, SENCAR mice treated according to the same protocol produced an equivalent response with maximal papilloma formation occurring 12 to 13 weeks earlier. Therefore, C57BL/6 mice exposed to B(a)P are capable of producing papillomas under certain experimental conditions. The inter-experimental variability of B(a)P-induced (50.5 micrograms/mouse) papilloma formation after 30 weeks of TPA promotion (2 micrograms/mouse, twice weekly) was examined in SENCAR mice over a 37-month period. Low statistical variation was observed in papilloma multiplicity, papilloma incidence, or papilloma latency. Male and female SENCAR mice produced equal values in the three parameters: 4.4 +/- 1.6 papillomas/mouse, 87% +/- 10% of the mice bearing papillomas, and 9.6 +/- 1.3 weeks (time at which 10% of the mice bore papillomas). The numbers of papillomas per mouse did not follow a Poisson distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Indications of repair of radon-induced chromosome damage in human lymphocytes: an adaptive response induced by low doses of X-rays.

Naturally occurring radon is a relatively ubiquitous environmental carcinogen to which large numbers of people can be exposed over their lifetimes. The accumulation of radon in homes, therefore, has led to a large program to determine the effects of the densely ionizing alpha particles that are produced when radon decays. In human lymphocytes, low doses of X-rays can decrease the number of chromatid deletions induced by subsequent high doses of clastogens. This has been attributed to the induction of a repair mechanism by the low-dose exposures. Historically, chromosome aberrations induced by radon have been considered to be relatively irreparable. The present experiments, however, show that if human peripheral blood lymphocytes are irradiated with low doses of X-rays (2 cGy) at 48 hr of culture, before being exposed to radon at 72 hr of culture, the yield of chromatid deletions induced by radon is decreased by a factor of two. Furthermore, the numbers of aberrations per cell do not follow a Poisson distribution but are overdispersed, as might be expected because high-linear energy transfer (high LET) alpha particles have a high relative biological effectiveness compared to low-LET radiations such as X-rays or gamma rays. Pretreatment with a low dose of X-rays decreases the overdispersion and leads to a greater proportion of the cells having no aberrations, or lower numbers of aberrations, than is the case in cells exposed to radon alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed2006

Photon-number-resolving detection at a telecommunications wavelength with a charge-integration photon detector.

We demonstrate multiphoton discrimination at a telecommunications wavelength with the readout frequency of 40 Hz by a charge-integration photon detector (CIPD). The CIPD consists of an InGaAs pin photodiode and a GaAs junction field effect transistor as a preamplifier in a charge-integration circuit, which is cooled to 4.2 K to reduce thermal noise. The quantum efficiency of the CIPD (the detector itself) is 80% for 1530 nm light, and the readout noise is measured as 0.26 electrons at 40 Hz. We can construct Poisson distributions of photocarrier numbers with distinct peaks at each photocarrier number, corresponding to a signal-to-noise ratio of about 3.

Journal Article↗