Percentage Of False Positives Research Articles

Evaluation of statistical association measures for the automatic signal generation in pharmacovigilance

Pharmacovigilance aims at detecting the adverse effects of marketed drugs. It is generally based on the spontaneous reporting of events thought to be the adverse effects of drugs. Spontaneous Reporting Systems (SRSs) supply huge databases that pharmacovigilance experts cannot exhaustively exploit without data mining tools. Data mining methods; i.e., statistical association measures in conjunction with signal generation criteria, have been proposed in the literature but there is no consensus regarding their applicability and efficiency, especially since such methods are difficult to evaluate on the basis of actual data. The objective of this paper is to evaluate association measures on simulated datasets obtained with SRS modeling. We compared association measures using the percentage of false positive signals among a given number of the most highly ranked drug-event combinations according to the values of the association measures. By considering 150 drugs and 100 adverse events, these percentages of false positives, among the 500 most highly ranked drug-event couples, vary from 1.1% to 53.4% (averages over 1000 simulated datasets). As the measures led to very different results, we could identify which measures appeared to be the most relevant for pharmacovigilance.

Cross-Reaction of Sera from Patients with Various Infectious Diseases with Leishmania infantum

Objective: To compare and evaluate the application of indirect fluorescent antibody (IFA) and counterimmunoelectrophoresis (CIEP) for laboratory identification of visceral leishmaniasis. Materials and Methods: Serum samples from patients with malaria (Plasmodium vivax, n = 86; Plasmodium falciparum, n = 38), brucellosis (n = 26), tuberculosis (n = 31) and typhoid fever (n = 35) were examined for the presence of antibody to Leishmaniainfantum antigen using IFA and CIEP tests. Results: Using IFA, false-positive results were malaria (P. vivax 19.8%, P. falciparum 13.2%), tuberculosis (6.4%), brucellosis (3.8%), and typhoid fever (2.8%). Using CIEP, a lower percentage of false-positives was observed only among malaria patients (P. vivax 2.3%, P. falciparum 2.6%). Serum samples from patients with other infectious diseases were negative in the CIEP test. Conclusion: Based on the results of this study, the CIEP technique is recommended for immunodiagnosis of visceral leishmaniasis, especially in regions where malaria, brucellosis and tuberculosis are prevalent.

Sample size for detecting differentially expressed genes in microarray experiments

BackgroundMicroarray experiments are often performed with a small number of biological replicates, resulting in low statistical power for detecting differentially expressed genes and concomitant high false positive rates. While increasing sample size can increase statistical power and decrease error rates, with too many samples, valuable resources are not used efficiently. The issue of how many replicates are required in a typical experimental system needs to be addressed. Of particular interest is the difference in required sample sizes for similar experiments in inbred vs. outbred populations (e.g. mouse and rat vs. human).ResultsWe hypothesize that if all other factors (assay protocol, microarray platform, data pre-processing) were equal, fewer individuals would be needed for the same statistical power using inbred animals as opposed to unrelated human subjects, as genetic effects on gene expression will be removed in the inbred populations. We apply the same normalization algorithm and estimate the variance of gene expression for a variety of cDNA data sets (humans, inbred mice and rats) comparing two conditions. Using one sample, paired sample or two independent sample t-tests, we calculate the sample sizes required to detect a 1.5-, 2-, and 4-fold changes in expression level as a function of false positive rate, power and percentage of genes that have a standard deviation below a given percentile.ConclusionsFactors that affect power and sample size calculations include variability of the population, the desired detectable differences, the power to detect the differences, and an acceptable error rate. In addition, experimental design, technical variability and data pre-processing play a role in the power of the statistical tests in microarrays. We show that the number of samples required for detecting a 2-fold change with 90% probability and a p-value of 0.01 in humans is much larger than the number of samples commonly used in present day studies, and that far fewer individuals are needed for the same statistical power when using inbred animals rather than unrelated human subjects.

Screening of developmental disorders in five-year-olds using the FTF (Five to Fifteen) questionnaire: a validation study

The study examined the validity of the Five to Fifteen (FTF) questionnaire in detecting developmental disorders in five-year-old children. A pilot study (N=70) was first undertaken to try out a translation of the FTF into Finnish. Subsequently, FTF questionnaires were mailed to parents of all five-year-old children from specified health-care districts in Vantaa, Finland. A total of 769 questionnaires (60%) were completed and returned. Children scoring above a cut-off value in any domain were considered at risk for having developmental disorders (the Risk Group; N=90). A Control Group was formed by randomly selecting 30 children who did not score above the threshold value in any domain. The children from the Risk Group and the Control Group were called to individual neuropsychological assessments. All invited children attended the assessments. The parts of the FTF that assess fine motor skills, executive functions (including attention and impulsivity), perception, memory, and language were used for this study. The external criterion measure was the NEPSY, a neuropsychological assessment instrument. Results demonstrated that the five FTF Domain Scores used in this study correlated significantly with the corresponding NEPSY Domain Scores. Second, the Risk Group obtained significantly poorer scores on the NEPSY than the Control Group. Third, on a cross-tabulation a very high rate of positive hits (93 %) was obtained as well as a very low rate of misses (7 %), indicating a very good sensitivity. However, there were a large percentage of false positives (63 %), indicating that specificity was not so good. Evidently, parents may report concerns related to the young child's development even when neuropsychological assessments do not indicate significant disorders. On the whole, the findings supported the validity of the FTF as a developmental screening instrument.

Direct screening of olive oil samples for residual benzene hydrocarbon compounds by headspace-mass spectrometry

The applicability of the direct coupling of headspace-mass spectrometry for the expeditious and reliable screening of olive oil samples for selected volatile organic compounds (viz. benzene, toluene, ethylbenzene, xylene isomers and styrene) has been evaluated. Samples were classified as recommendable or non-recommendable for human consumption taking into account the average concentration of the target analytes in virgin olive oil. The cut-off level was fixed at a global concentration of BTEXS of 0.2 μg ml −1, and several pattern recognition techniques were used in the data treatment. The reliability of the proposed screening method was evaluated in terms of the percentage of false positives and false negatives. No false negatives were obtained, while the percentage of false positives were 5% when using CA and PCA techniques. However, SIMCA yielded the best percentage of prediction as neither false negatives nor positives were obtained. Finally, a total of 50 commercial virgin olive oil samples were analyzed and only four samples gave a BTEXS concentration over the cut-off.

Increased identification of peptides by enhanced data processing of high-resolution MALDI TOF/TOF mass spectra prior to database searching.

This paper presents application of sequential enhanced data processing procedures to high-resolution tandem mass spectra for identification of peptides using the Mascot database search algorithm. A strategy for (1) selection of fragment ion peaks from MS/MS spectra, (2) utilization of improved mass accuracy of the precursor ions, and (3) wavelet denoising of the mass spectra prior to fragment ion selection have been developed. The number of peptide identifications obtained using the enhanced processing was then compared with that obtained using software provided by the instrument manufacturer. Approximately 9000 MS/MS spectra acquired by the Applied Biosystems 4700 TOF/TOF MS instrument were used as a model data set. After application of the new processing, an increase of 33% unique peptides and 22% protein identifications with at least two unique peptides were found. The influence of the processing on the percentage of false positives, estimated by searching against a randomized database, was estimated to increase false positive identifications from 2.7 to 3.9%, which was still below the 5% error rate specified in the Mascot search. These data processing approaches increase the amount of information that can be extracted from LC-MS analysis without the necessity of additional experiments.

Three new consensus QSAR models for the prediction of Ames genotoxicity.

Three QSAR methods, artificial neural net (ANN), k-nearest neighbors (kNN), and Decision Forest (DF), were applied to 3363 diverse compounds tested for their Ames genotoxicity. The ratio of mutagens to non-mutagens was 60/40 for this dataset. This group of compounds includes >300 therapeutic drugs. All models were developed using the same initial set of 148 topological indices: molecular connectivity chi indices and electrotopological state indices (atom-type, bond-type and group-type E-state), as well as binary indicators. While previous studies have found logP to be a determining factor in genotoxicity, it was not found to be important by any modeling method employed in this study. The three models yielded an average training/test concordance value of 88%, with a low percentage of false positives and false negatives. External validation testing on 400 compounds not used for QSAR model development gave an average concordance of 82%. This value increased to 92% upon removal of less reliable outcomes, as determined by a reliability criterion used within each model. The ANN model showed the best performance in predicting drug compounds, yielding 97% concordance (34/35 drugs) after the removal of less reliable predictions. The appreciable commonality found among the top 10 ranked descriptors from each model is of particular interest because of the diversity in the learning algorithms and descriptor selection techniques employed in this study. Forty percent of the most important descriptors in any one model are found in one or two other models. Fourteen of the most important descriptors relate directly to known toxicophores involved in potent genotoxic responses in Salmonella typhimurium. A comparison of the validation results with those of MULTICASE and DEREK indicated that the new models presented in this work perform substantially better than the former models in predicting genotoxicity of therapeutic drugs. Substantially higher specificity was achieved with these new models as compared with MULTICASE or DEREK with comparable sensitivities among all models.

Toward a Direct Brain Interface Based on Human Subdural Recordings and Wavelet-Packet Analysis

Highly accurate asynchronous detection of movement related patterns in individual electrocorticogram channels has been shown using detection based on either event-related potentials (ERPs) or event-related desynchronization and synchronization (ERD/ERS). A method using wavelet-packet features selected with a genetic algorithm was proposed to simultaneously detect ERP and ERD/ERS and was tested on data from seven subjects and four motor tasks. The proposed wavelet method performed better than previous methods with perfect detection for four subject/task combinations and hit percentages greater than 90% with false positive percentages less than 15% for at least one task for all seven subjects.

Accuracy of methods to estimate ionized and “corrected” serum calcium concentrations in critically ill multiple trauma patients receiving specialized nutrition support

The purpose of this study was to determine the accuracy of 22 published methods to estimate serum ionized calcium (iCa) and "corrected" total serum calcium (totCa) concentrations in critically ill, multiple trauma patients. Seven of these formulas estimated iCa and 15 were directed toward predicting a "corrected" totCa. Adult patients admitted to the trauma intensive care unit who received specialized nutrition support were consecutively recruited for study. Patients who received blood products, i.v. calcium, or therapeutic doses of heparin within 24 hours before the laboratory measurements or had a history of cancer, bone disease, parathyroid disease, hyperphosphatemia (> or = 6 mg/dL), hyperbilirubinemia (> 3.5 mg/dL), or renal failure requiring dialysis were excluded. The 22 published methods were analyzed for sensitivity, specificity, percentage false negatives, and percentage false positives for predicting hypocalcemia or hypercalcemia. One hundred patients were studied 4.9 +/- 3.3 days postinjury and were receiving enteral nutrition (n = 81), parenteral nutrition (n = 18), or both (n = 1) at the time of study. Twenty-one patients were hypocalcemic (iCa < or = 1.12 mmol/L) and 6 were hypercalcemic (iCa > or = 1.32 mmol/L). The mean sensitivity of the 22 methods for assessing hypocalcemia was 25% +/- 32% and the specificity was 90% +/- 18%. Although the average percentage of false positives for assessing hypocalcemia was 10% +/- 18%, the mean percentage of false negatives was inordinately high at 75% +/- 32%. The most common method for determination of "corrected" totCa concentration ["corrected" calcium = totCa + (0.8 x (4-serum albumin concentration))] had a sensitivity of only 5%. The McLean-Hastings nomogram method, the most common method for estimating serum iCa concentration, had a sensitivity of 67% but unfortunately also had a significant false-positive rate of 27%. Serum totCa correlated modestly with iCa (r2 = .334, p < .001). Those patients with a serum albumin < or = 2 g/dL (n = 43) had a significantly higher prevalence of hypocalcemia than those with a higher serum albumin concentration (37% incidence of hypocalcemia vs 10%, respectively, p < .002). Aberrations in calcium homeostasis are frequent (27%) in postresuscitative critically ill multiple trauma patients. Methods for predicting hypocalcemia lack sensitivity and are often associated with an unacceptable rate of false negatives. Predictive methods for estimating ionized or corrected serum concentrations should not be used. Direct measurement of serum iCa concentration is indicated for assessing calcium status for this population.

Multicentre quality control study for detection of Mycobacterium tuberculosis in clinical samples by nucleic amplification methods

The aim of this study was to evaluate the laboratory performance of nucleic acid amplification tests (NATs) for detection of the Mycobacterium tuberculosis complex. A proficiency panel consisting of eight sputum specimens and four specimens diluted in phosphate-buffered saline (PBS) was sent to 82 laboratories in 23 countries by the Quality Control for Molecular Diagnostics (QCMD) TB programme. The performance of different NATs was analysed in combination with a questionnaire on the applied methods. Seventy-eight participants (95.2%) contributed a total of 85 evaluable data sets. The percentage of correct results on the eight sputum samples was 86.3% (586/679). Of the sputum specimens considered as 'smear-negatives' (650 CFU/250 micro L), only 61.2% (104/170) were reported positive. The percentage of correct results for the three scored PBS samples was 75.7% (193/255). The total number of false-positive results was 11 (4.3%); these were reported for seven (8.2%) of the 85 data sets. In 32 (37.6%) data sets an 'in-house' NAT method was used, and in 53 (62.4%) sets a commercial assay was tested. The percentage of data sets achieving correct results on all sputum samples was 35.3% and 37.8%, respectively. For the PBS samples this was 45.8% and 41.5%. Overall, the results of this study demonstrated that the performance of NATs for the detection of M. tuberculosis has improved since previous studies. The percentage of false-positives has decreased considerably. However, a large number of procedures still lack sufficient sensitivity for application to smear-negative samples.

Increased rate of visual field loss associated with larger initial visual field threshold values on follow-up of open-angle glaucoma.

To determine the changes in the visual field over time and the factors that contribute to these changes on follow-up of open-angle glaucoma patients. From a retrospective review of patients' charts and visual fields, 30 eyes from 30 patients with open-angle glaucoma with a minimum of 3 years of follow-up were chosen. Visual fields were obtained with the Octopus perimeter about every 4 months. Regression analysis was used to obtain the slope for all the threshold values for each eye for the total field and nine different regions over time. Optic disc area was measured from single fundus photographs obtained at the beginning of the period of observation. The open-angle glaucomas were observed for a mean of 6.7 +/- 2.3 years. The number of visual fields per eye was 20.7 +/- 8.0. The mean threshold value of the total field for the first three visual fields was 18.0 +/- 5.2 dB. The visual fields of the 30 eyes with a mean intraocular pressure of 18 +/- 2 mm Hg during follow-up showed a significant decrease in their visual field slope of -0.384 dB/y for the total visual field. On multivariate analysis, the slope or rate of visual field loss was significantly correlated with the average of the first three initial visual field thresholds for the total visual field, temporal, and central regions so that the greater the threshold value the more rapid the rate of the visual field loss. For the total visual field and for the nasal, superior nasal, and temporal regions with lower initial threshold values, the rate of visual field loss was curvilinear with the rate of visual field loss increasing at greater initial mean threshold values. The other regions of the visual field showed a linear increasing rate of visual field loss with larger initial threshold values. Other factors significantly associated with progression of visual field loss were refractive error, race, the slope of the pulse rate, and the mean percent false positives and false negatives for initial to final observations. The mean and the slope of intraocular pressure from initial to final observation were not significant variables. In open-angle glaucomas observed for 6.7 +/- 2.3 years, there was a more rapid rate of visual field loss associated with larger initial threshold values and a less rapid rate of visual field loss associated with smaller initial threshold values indicating that the progression of visual field loss is greater in an earlier stage of disease.

Optimal screening distance for ulnar neuropathy at the elbow.

Focal demyelinating lesions typically occur within a 1-cm segment of a nerve. In electrodiagnostic studies, measurements over longer distances decrease the chance of detecting such lesions, but measurements over shorter distances result in greater experimental error. Our objective was therefore to determine the optimal screening distance for ulnar neuropathy at the elbow (UNE) incorporating previously derived experimental errors for calculating nerve conduction velocity (NCV). Using a lesion model wherein prolongation of 0.4 ms was added to the expected latency of a 1-cm nerve segment, new NCVs were derived for distances between 1 and 10 cm for nerves normally conducting between 40 and 65 m/s. Lesion detection, or sensitivity, was defined as the likelihood of calculating a decrease of 10 m/s from the normal NCV while including the experimental error. Specificity was related to the likelihood of an inadvertent calculation of such a decrease in NCV in a segment without a lesion. Sensitivity and specificity were derived at multiple distances with varying NCVs. The total percentage error was the sum of the false-negative and false-positive percentages. The least total percentage error occurred at 3-4 cm, 4-6 cm, and 6-8 cm for nerves normally conducting at 40-50 m/s, 50-60 m/s, and 60-65 m/s, respectively. We conclude that the optimal distance for screening UNE, considering both sensitivity and specificity, is significantly less than 10 cm, perhaps as low as 4-6 cm; considering in addition the likely locations of focal lesions, the best distance is 6-8 cm.

Pitfalls of the synthetic lethality screen in Saccharomyces cerevisiae: an improved design

The colony color assay in yeast enables the visual identification of plasmid-loss events. In combination with a plasmid-dependence assay, it is commonly used to identify synthetic interactions between functionally related genes. Frequently, the plasmid carries the ADE3 gene and mutants are recognized as red colonies that fail to produce sectors. In these assays, a high percentage of false-positives is obtained, most of which result from synthetic lethality with the ade3 mutation. Here, we study the nature of these mutants. We report that mutations in the HIP1 and SHM1 genes exhibit synthetic lethality with ade3 deletions. A similar interaction is found between the fur1 and ura3 mutations. Lethality in the absence of the mitochondrial Shm1 and the cytoplasmic Ade3 enzymes indicates that, under certain circumstances, these cellular compartments cooperate in carrying out essential metabolic processes. In addition, we report the identification of a truncated ADE3 allele with a unique coloration phenotype and show that it can be used to improve synthetic lethal screens.

Improving the accuracy of mammography: volume and outcome relationships.

Countries with centralized, high-volume mammography screening programs, such as the U.K. and Sweden, emphasize high specificity (low percentage of false positives) and high sensitivity (high percentage of true positives). By contrast, the United States does not have centralized, high-volume screening programs, emphasizes high sensitivity, and has lower average specificity. We investigated whether high sensitivity can be achieved in the context of high specificity and whether the number of mammograms read per radiologist (reader volume) drives both sensitivity and specificity. The U.K.'s National Health Service Breast Screening Programme uses the PERFORMS 2 test as a teaching and assessment tool for radiologists. The same 60-film PERFORMS 2 test was given to 194 high-volume U.K. radiologists and to 60 U.S. radiologists, who were assigned to low-, medium-, or high-volume groups on the basis of the number of mammograms read per month. The standard binormal receiver-operating characteristic (ROC) model was fitted to the data of individual readers. Detection accuracy was measured by the sensitivity at specificity = 0.90, and differences among sensitivities were determined by analysis of variance. The average sensitivity at specificity = 0.90 was 0.785 for U.K. radiologists, 0.756 for high-volume U.S. radiologists, 0.702 for medium-volume U.S. radiologists, and 0.648 for low-volume U.S. radiologists. At this specificity, low-volume U.S. radiologists had statistically significantly lower sensitivity than either high-volume U.S. radiologists or U.K. radiologists, and medium-volume U.S. radiologists had statistically significantly lower sensitivity than U.K. radiologists (P<.001, for all comparisons). Reader volume is an important determinant of mammogram sensitivity and specificity. High sensitivity (high cancer detection rate) can be achieved with high specificity (low false-positive rate) in high-volume centers. This study suggests that there is great potential for optimizing mammography screening.

Two-Stage Equating in Differential Item Functioning Detection under the Graded Response Model with the Raju Area Measures and the Lord Statistic

The differential item functioning (DIF) detection in polytomous response items is an area of study of recent interest. Cohen and colleagues proposed a polytomous extension of the Lord statistic and the Raju exact area measures, when the items fit the graded response model. This study examined the effects of test purification in detecting DIF by means of polytomous extensions of the Raju area measures and the Lord statistic. The factors manipulated were percentage of DIF items in the test (5%, 10%, and 20%), amount of DIF (0.2, 0.4, and 0.8), sample size (250, 500, and 1,000) and test purification (noniterative versus two-stage). The results of this study suggest that the use of the two-stage equating procedure with Z(SA) and χ2-LORD reduces the percentage of false positives and improves the detection of DIF.

Assessing gene significance from cDNA microarray expression data via mixed models.

The determination of a list of differentially expressed genes is a basic objective in many cDNA microarray experiments. We present a statistical approach that allows direct control over the percentage of false positives in such a list and, under certain reasonable assumptions, improves on existing methods with respect to the percentage of false negatives. The method accommodates a wide variety of experimental designs and can simultaneously assess significant differences between multiple types of biological samples. Two interconnected mixed linear models are central to the method and provide a flexible means to properly account for variability both across and within genes. The mixed model also provides a convenient framework for evaluating the statistical power of any particular experimental design and thus enables a researcher to a priori select an appropriate number of replicates. We also suggest some basic graphics for visualizing lists of significant genes. Analyses of published experiments studying human cancer and yeast cells illustrate the results.

Analysis and localization of epileptic events using wavelet packets

This article compares results obtained in previous studies using time–frequency representations (Wigner–Ville, Choi–Williams and Parametric) and the wavelet transform with those obtained with wavelet packet functions to show new findings about their quality in the analysis of ECoG recordings in human intractable epilepsy: data from 21 patients have been analyzed and processed with four types of wavelet functions, including Orthogonal, Biorthogonal and Non-Orthogonal basis. These functions were compared in order to test their quality to represent spikes in the ECoG. The energy based on the wavelet coefficients to different scales was also calculated. The best results were found with the biorthogonal-6.8 wavelet on 5–7 scales, which gave 0.92 sensitivity, but with a high percentage of false positives; this representation was highly correlated with spike events on time and duration. To improve these results we have studied the wavelet packet coefficients energy. We found that reconstruction wavelet packet coefficients at 4 and 9 nodes contain significant information to characterize the spike event. These nodes' reconstruction coefficients were multiplied and this product was highly correlated with spikes events on time and duration. With this procedure we improved the sensitivity up to 0.96 with the same biorthogonal-6.8 wavelet at four levels. With this technique we do not sacrifice computation time: 896 samples are processed at only 0.16 s, so that it is possible to show the spike scattering path on line, because 896 samples (7 s)/16 channels are processed at 3.13 s.

Maternal or fetal origin of rhesus monkey (Macaca mulatta) amniotic fluid leukocytes can be identified by polymerase chain reaction using the zinc finger Y gene.

Leukocytes can be found in substantial numbers within the intrauterine tissues and amniotic fluid of women, and play a central role in the pathophysiology of infection-related preterm labor by their production of proinflammatory mediators. It remains unclear whether these leukocytes represent a fetal immune response, a maternal response, or a combination of the two. The objective of this study was to develop a test in the rhesus monkey (Macaca mulatta) suitable for determining the percentage of male fetal cells present in a population of leukocytes recovered from blood or amniotic fluid. We found inadequate specificity for rhesus monkey cells using commercial human Y-chromosome paint kits (fluorescence in situ hybridization (FISH)). Human-specific primers for the repetitive Y chromosome DYZ-1 locus employed in the polymerase chain reaction (PCR) produced an unacceptable percentage of false positives. However, we successfully developed a PCR-based test using rhesus-specific primers for the zinc finger Y (ZFY) locus. Densitometry of PCR products from known ratios of male and female adult peripheral leukocytes generated a linear standard curve which provided quantitative results and required only 400 cells per sample. The rhesus beta globin (RBG) gene served as an internal control. The PCR test correctly discriminated the sex of peripheral leukocytes in 20 adult males, 20 adult females, two male fetuses, and one female fetus. Serial samples of amniotic fluid from four chronically catheterized rhesus monkeys bearing male fetuses were used to confirm the utility of this assay for quantifying fetal cells in amniotic fluid. In conclusion, we have developed a PCR test which is suitable for distinguishing male from female cells in adult and fetal blood and in amniotic fluid, which lends itself to a variety of diagnostic and biologic applications in the rhesus monkey and potentially in other nonhuman primates.

Modeling of combined processing steps for reducing Escherichia coli O157:H7 populations in apple cider.

Probabilistic models were used as a systematic approach to describe the response of Escherichia coli O157:H7 populations to combinations of commonly used preservation methods in unpasteurized apple cider. Using a complete factorial experimental design, the effect of pH (3. 1 to 4.3), storage temperature and time (5 to 35 degrees C for 0 to 6 h or 12 h), preservatives (0, 0.05, or 0.1% potassium sorbate or sodium benzoate), and freeze-thaw (F-T; -20 degrees C, 48 h and 4 degrees C, 4 h) treatment combinations (a total of 1,600 treatments) on the probability of achieving a 5-log(10)-unit reduction in a three-strain E. coli O157:H7 mixture in cider was determined. Using logistic regression techniques, pH, temperature, time, and concentration were modeled in separate segments of the data set, resulting in prediction equations for: (i) no preservatives, before F-T; (ii) no preservatives, after F-T; (iii) sorbate, before F-T; (iv) sorbate, after F-T; (v) benzoate, before F-T; and (vi) benzoate, after F-T. Statistical analysis revealed a highly significant (P < 0.0001) effect of all four variables, with cider pH being the most important, followed by temperature and time, and finally by preservative concentration. All models predicted 92 to 99% of the responses correctly. To ensure safety, use of the models is most appropriate at a 0.9 probability level, where the percentage of false positives, i.e., falsely predicting a 5-log(10)-unit reduction, is the lowest (0 to 4.4%). The present study demonstrates the applicability of logistic regression approaches to describing the effectiveness of multiple treatment combinations in pathogen control in cider making. The resulting models can serve as valuable tools in designing safe apple cider processes.

Reducción de la prevalencia de los defectos de cierre del tubo neural mediante un programa regional de cribado con alfafetoproteína en suero materno

ObjectiveOptimization of a maternal serum alphafetoprotein screening as a regional programme, in order to reduce neural tube defect prevalence in the Principado de Asturias (Spain) Patients and methodsThe participants are pregnant women from everywhere in Asturias regardless their origin, public or private asistance. We have studied 63,163 pregnancies between 1987 and 1998. All the biochemical techniques were performed at the Biochemistry Laboratory in San Agustín Hospita ResultsWe have optimized the maternal serum alphafetoprotein screening programme with low percentages of false positives as well as performed amniocentesis, 1.9% and 0.5% respectively. We have observed that maternal serum alphafetoprotein values are higher in the presence of anencephaly than in a fetus with open spina bifida. The prevalence of these defects was diminished from 1.3% to near zero ConclusionsIt is necessary a multidisciplinary team in a screening programme like this, in order to be successful. After several years, the obstetricians and gynecologists are using the maternal serum alphafetoprotein as a routine screening tool in the pregnancy protocol. This screening programme has achieved to diminish the prevalence of open neural tube defects and it has let to know a lot more about these defects in Asturias