Molecular diagnosis of myotonic dystrophy.
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OBJECTIVES: To investigate the prevalence and risk factors of HSV-1 and HSV-2 antibodies in HIV infected women and the association between recurrent genital ulcerations and HIV disease progression in HSV-2 positive women. METHODS: The presence of HSV antibodies was tested in 276 of the 487 women participating in a European cohort study of HIV infected women. Prevalence rate ratios described the association between HSV infection and its risk factors, using log binomial regression. Generalised estimating equations (GEE) analysis was performed to determine the impact of markers of HIV disease progression on recurrent genital ulcerations. RESULTS: The prevalence of HSV-1 and HSV-2 antibodies was 76% (95% confidence interval (95% CI): 71-81) and 42% (95% CI: 36-50); 30% (95% CI: 24-35) of the women had antibodies against both HSV-1 and HSV-2. The prevalence of HSV-1 was 86% (95% CI: 80-92) in southern Europe compared with 69% (95% CI: 57-79) and 67% (95% CI: 55-77) in central and northern Europe (p=0.002). This geographical variation remained after adjustment for other risk factors. An increasing number of years of sexual activity (p=0.0002) and a history of prostitution (p=0.0001) were independently associated with HSV-2 prevalence. In HSV-2 positive women, symptomatic cases of HSV infection were minimal, but increased with decreasing CD4 count. CONCLUSION: In HIV infected women, the prevalence of HSV antibodies is high and symptomatic cases of HSV infection are minimal, but increase with decreasing CD4 count. HSV-2 but not HSV-1 was related to sexual behaviour (that is, a history of prostitution and the number of sexually active years) in this group of HIV infected women.
BACKGROUND: We have previously suggested that it is possible to predict oxygen desaturation during flight in children with cystic fibrosis and chronic lung disease by non-invasive measurement of oxygen saturation following inhalation of 15% oxygen--the pre-flight hypoxic challenge. This study reports on the results of measurements over 5 years. METHODS: The study comprised a pre-flight hypoxic challenge measuring oxygen saturation by finger tip pulse oximetry (SpO(2)) during tidal breathing of 15% oxygen in nitrogen and spirometric testing 1 month before the flight followed by SpO(2) measurements during intercontinental flights to and from holidays abroad with children in wake and sleep states. RESULTS: Pre-flight tests were completed on 87 children with cystic fibrosis. Desaturation of <90% occurred in 10 children at some stage during the flight, three of whom received supplementary oxygen. Using a cut off SpO(2) of 90%, the pre-flight hypoxic challenge correctly predicted desaturation in only two of these children. The sensitivity and specificity of the pre-flight hypoxic challenge were 20% and 99%, respectively, compared with 70% and 96% for spirometric tests (using a cut off for forced expiratory volume in 1 second (FEV(1)) of <50% predicted). Overall, pre-flight spirometric tests were a better predictor of desaturation during flight with the area under the Receiver Operating Characteristic (ROC) curve of 0.89 compared with 0.73 for the hypoxic challenge test. CONCLUSIONS: In this group of subjects pre-flight spirometric testing was a better predictor of desaturation during flight than the pre-flight hypoxic challenge.
In this paper, we extend the Hierarchical Mixture of Experts (HME) to temporal processing and explore it for a substantial problem, that of text-dependent speaker identification. For a specific multiway classification, we propose a generalized Bernoulli density instead of the multinomial logit density to avoid the instability during training. Time-delay technique is applied for spatio-temporal processing in the HME and a combining scheme is presented for combining multiple time-delay HMEs in order to complete a multi-scale analysis for the temporal data. Using the time-delay HME along with the EM algorithm as well as the combination of multiple time-delay HMEs, the speaker identification system has a good performance and yields significantly fast training. We have also addressed some issues about the time-delay techniques in the HME.
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This study aimed at examining correlations between quantitative REM sleep EEG, regional cerebral blood flow measured by single photon emission computerized tomography (SPECT) and global cognitive functioning in nine patients with mild to moderate Alzheimer's disease. REM sleep EEG was not correlated with SPECT measures in any of the 6 regions studied. However, degrees of interhemispheric asymmetry calculated by both measures were concordant for the parieto-occipital region. Mini-mental state score correlated with REM sleep EEG slowing for left frontal, left and right parieto-occipital and left temporal regions but was not correlated with SPECT measures for any of the six regions. These results suggest that quantitative REM sleep EEG would be more useful than SPECT for evaluating cerebral dysfunctions in mild to moderate Alzheimer's disease.
We derive analytically the solution for the output rate of the ideal coincidence detector. The solution is for an arbitrary number of input spike trains with identical binomial count distributions (which includes Poisson statistics as a special case) and identical arbitrary pairwise cross-correlations, from zero correlation (independent processes) to complete correlation (identical processes).
In this letter, we extend our previous analytical results (Mikula & Niebur, 2003) for the coincidence detector by taking into account probabilistic frequency-dependent synaptic depression. We present a solution for the steady-state output rate of an ideal coincidence detector receiving an arbitrary number of input spike trains with identical binomial count distributions (which includes Poisson statistics as a special case) and identical arbitrary pairwise cross-correlations, from zero correlation (independent processes) to perfect correlation (identical processes). Synapses vary their efficacy probabilistically according to the observed depression mechanisms. Our results show that synaptic depression, if made sufficiently strong, will result in an inverted U-shaped curve for the output rate of a coincidence detector as a function of input rate. This leads to the counterintuitive prediction that higher presynaptic (input) rates may lead to lower postsynaptic (output) rates where the output rate may fall faster than the inverse of the input rate.
Dental prophylaxis with APF gels (1.23%) may cause gastric distress as a side-effect. This gastric irritation is probably due to a direct toxic effect of fluoride (F), swallowed in conjunction with the treatment, on the gastric mucosa. The aim of the present study was to investigate whether--and to what extent--a dental treatment with 3 g of a 0.42%-F gel could affect the gastric mucosa due to inadvertent swallowing of the gel. Ten subjects underwent a control gastroscopy, and two weeks later, a second gastroscopy was performed two h after a F gel treatment. During the gastroscopy, the mucosa was examined and the injuries graded according to an arbitrary scale. Four biopsies of the antral and corpus regions of the stomach were taken and evaluated histologically. The mean (+/- SD) amount of F retained after the application was 5.1 +/- 2.1 mg, i.e., 40% of the applied amount of F. Petechiae and erosions were found in the mucosa in seven of the ten patients. The histopathological evaluation revealed changes in nine of ten patients, with the surface epithelium as the most affected component of the mucosa. The present study clearly shows that a treatment with a F gel of rather low F concentration may result in injuries to the gastric mucosa. The importance of current recommended guidelines so that the amount of F swallowed during a gel application can be minimized is emphasized. From a toxicological standpoint, the use of a low-F gel instead of a 1.23%-F gel in small children is recommended for avoidance of adverse gastric effects.
This study examined endosseous cylinder implant survival, defined as the unqualified presence of the implant in the mouth at the end of the observation period, in 598 consecutive VA patients, with a total of 2098 implants. Data were taken from the Department of Veterans Affairs (VA) Dental Implant Registry, which has maintained longitudinal data on the survival of individual dental implants in VA patients since 1987. The maximum time of observation in any one patient was 2040 days (5.6 yr). Survival analysis by use of life-table methods was carried out on both an implant- and a patient-specific basis. Implant cases were accrued randomly, and therefore a random censoring model was used. A correlated binomial model was used for assessment of the degree of within-patient clustering of implant removals. Results showed that the implant-specific survival rate during the longest time interval (5.6 yr) was 89.9%; the patient-specific implant survival rate during the same time was 78.2%. Among implants which were removed, the mean time to removal was 292 days. The hazard function, which describes the probability of implant loss as a function of time, decreased steadily throughout the observation period. The correlated binomial model suggested a clustering of removals within patients with multiple implants (rho = 0.11, p = 0.0001). The odds of having a second implant removed were 1.3 times greater if the patient had already had one implant removed. This study suggests that when implants fail, they do so soon after placement, and the likelihood of failure decreases steadily from implantation through the first five years post-surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
Sealants are highly effective in preventing dental caries in the pits and fissures of teeth when applied by trained operators in clinical trials and public health programs. The effectiveness of fissure sealants when applied in dental practices is still not known. The purpose of this longitudinal study was to evaluate the effectiveness of fissure sealants applied in dental practices in preventing dental caries on occlusal surfaces of first permanent molars. In 1990, on the Island of Montréal, 911 randomly selected children, from 6 to 9 years of age, were examined; out of those, 816 and 733 were re-examined in 1991 and 1992, respectively. Only the 733 children with complete examination records were included in this evaluation. Sealant applications were either personally paid for or were paid for by private dental insurers. All children were covered for diagnosis and restorative care by a publicly financed and universal insurance program. Dental treatment records were provided by Quebec's health insurance board. In the epidemiological examination, the occlusal surfaces of first permanent molars, which are the only surfaces included in this analysis, were classified into: sound, non-cavitated and cavitated status, restored, and sealed. Sealants were evaluated for full or partial coverage of the occlusal surface and presence of dental caries. During the first and second years, 11.6% and 17.5% of the students had new sealants. The number of new sealants placed during the two years was 507. Children with caries-free status and whose parents had high school education or higher were significantly more likely to receive sealants during the study.(ABSTRACT TRUNCATED AT 250 WORDS)
This Monte Carlo study compares performance of the linear and the logistic mixed-model analyses of simulated community trials having event rates of 37%, 13%, or 5%, intraclass correlations between 0.01 and 0.05, and 17 or 5 denominator degrees of freedom. Type I or Type II error rates showed no essential difference between the two analysis methods. They showed depressed error rates when the event rate or the denominator degrees of freedom were small. The authors conclude that in studies with adequate denominator degrees of freedom, the researcher may use either method of analysis but should accept negative estimates of components of variance to avoid depression of error rates.
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Sexual abstinence programs have the potential to reduce the incidence of unplanned pregnancies and sexually transmitted diseases (STDs) among adolescents. Effectiveness measures are needed to help researchers assess the impact of sexual abstinence promotion programs on STD and pregnancy rates and to enable comparisons of abstinence effectiveness with other contraception and STD prevention methods. Abstinence "failure rates" have been proposed as one measure of program effectiveness. However, the concept of abstinence failure rates has not been adequately operationalized. The present study examines a novel mathematical framework for estimating abstinence failure rates, both theoretically and empirically. Examples are provided, and the advantages and disadvantages associated with the mathematical model-based approach are discussed.
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BACKGROUND: Genes that are determined to be significantly differentially regulated in microarray analyses often appear to have functional commonalities, such as being components of the same biochemical pathway. This results in certain words being under- or overrepresented in the list of genes. Distinguishing between biologically meaningful trends and artifacts of annotation and analysis procedures is of the utmost importance, as only true biological trends are of interest for further experimentation. A number of sophisticated methods for identification of significant lexical trends are currently available, but these methods are generally too cumbersome for practical use by most microarray users. RESULTS: We have developed a tool, LACK, for calculating the statistical significance of apparent lexical bias in microarray datasets. The frequency of a user-specified list of search terms in a list of genes which are differentially regulated is assessed for statistical significance by comparison to randomly generated datasets. The simplicity of the input files and user interface targets the average microarray user who wishes to have a statistical measure of apparent lexical trends in analyzed datasets without the need for bioinformatics skills. The software is available as Perl source or a Windows executable. CONCLUSION: We have used LACK in our laboratory to generate biological hypotheses based on our microarray data. We demonstrate the program's utility using an example in which we confirm significant upregulation of SPI-2 pathogenicity island of Salmonella enterica serovar Typhimurium by the cation chelator dipyridyl.
BACKGROUND: Response-adaptive randomization procedures have a long history in the theoretical statistics literature over the past four decades. The main idea historically was to develop randomization procedures that place fewer patients on the inferior treatment. More recent research has changed the main focus to that of usual considerations in typical clinical trials: power, sample size, expected treatment failures, maintaining randomization, among others. METHODS: We describe response-adaptive randomization procedures for simple clinical trials comparing two binomial success probabilities, including the randomized play-the-winner rule, the drop-the-loser rule, and a modification of the doubly-adaptive biased coin design. We treat as our principal goal minimizing expected treatment failures while preserving power and randomization. Based on some recent theoretical literature, the basic guidelines for selecting an appropriate procedure include targeting optimal allocation, having small variability, and preserving randomization. We use simulation to compare power and expected treatment failures according to these guidelines. RESULTS: When the two treatments had high probabilities (> 0.5) of success, the randomized play-the-winner rule was less powerful than complete randomization and the drop-the-loser rule by 1-3 percent with slightly larger expected number of treatment failures than the drop-the-loser rule. For all the success probabilities we examined, the drop-the-loser rule was within 1 percent of the power of complete randomization with a modest reduction of treatment failures. The doubly-adaptive biased coin design was as powerful or slightly more powerful than complete randomization in every case and expected treatment failures were always less, with modest reductions of the order of 0.3 percent to 8.3 percent. CONCLUSIONS: We conclude that the drop-the-loser rule and a modification of the doubly-adaptive biased coin design are the preferred procedures, and simulations show that these procedures yield a modest reduction in expected treatment failures while preserving power over complete randomization.