Generation mean analysis in relation to polygenic systems with epistasis and fixed genes

Epistatic effects involving genic combinations of fixed and non fixed genes are shown to contribute to the genotypic mean of any population. These effects define specific additive x additive and additive x dominant epistatic components. As such components are not estimable, their relative importance cannot be assessed. These epistatic effects can cause bias in the estimates of the additive and dominance components to which they are confounded. The magnitude of the bias depends on the relative values of the epistatic effects, comparatively to deviations d and h, type of prevailing epistasis and direction of dominance.

Impact of increasing mean air temperature on the development of rice and red rice

The objective of this study was to assess the development response of cultivated rice and red rice to different increases in minimum and maximum daily air temperatures, in Santa Maria, Rio Grande do Sul State, Brazil. One hundred years climate scenarios of temperatures 0, +1, +2, +3, +4, and +5ºC, with symmetric and asymmetric increases in minimum and maximum daily air temperatures were created, using the LARS-WG Weather Generator, and a 1969-2003 database. Nine cultivated rice genotypes (IRGA 421, IRGA 416, IRGA 417, IRGA 420, BRS 7 TAIM, BR-IRGA 409, EPAGRI 109, EEA 406 and a hybrid), and two red rice biotypes (awned black hull-ABHRR, and awned yellow hull-AYHRR) were used. The dates of panicle differentiation (R1), anthesis (R4), and all grains with brown hulls (R9) were estimated with a nonlinear simulation model. Overall, the duration of the emergence-R1 phase decreased, whereas the duration of the R1-R4 and R4-R9 phases most often increased, as temperature increased in the climate change scenarios. The simulated rice development response to elevated temperature was not the same, when the increase in minimum and maximum temperature was symmetric or asymmetric.

Positive predictive values of Breast Imaging Reporting and Data System (BI-RADS®) categories 3, 4 and 5 in breast lesions submitted to percutaneous biopsy

Objective To evaluate the BI-RADS as a predictive factor of suspicion for malignancy in breast lesions by correlating radiological with histological results and calculating the positive predictive value for categories 3, 4 and 5 in a breast cancer reference center in the city of São Paulo. Materials and Methods Retrospective, analytical and cross-sectional study including 725 patients with mammographic and/or sonographic findings classified as BI-RADS categories 3, 4 and 5 who were referred to the authors' institution to undergo percutaneous biopsy. The tests results were reviewed and the positive predictive value was calculated by means of a specific mathematical equation. Results Positive predictive values found for categories 3, 4 and 5 were respectively the following: 0.74%, 33.08% and 92.95%, for cases submitted to ultrasound-guided biopsy, and 0.00%, 14.90% and 100% for cases submitted to stereotactic biopsy. Conclusion The present study demonstrated high suspicion for malignancy in lesions classified as category 5 and low risk for category 3. As regards category 4, the need for systematic biopsies was observed.

Heritability at family mean level

Based on a polygenic system of a diploid species, without epistasis, and a population in Hardy-Weinberg equilibrium, without inbreeding and under linkage equilibrium, it can be shown that: (1) the narrow sense heritability at half-sib family level is equal to the square of the correlation coefficient between family mean and the additive genetic value of its common parent; (2) the narrow sense heritability at full-sib family level is equal to the square of the correlation coefficient between family mean and the mean of the additive genetic values of its parents; (3) the narrow sense heritability at Sn family level is exactly equal to the square of the correlation coefficient between family mean and the additive genetic value of its parent only in absence of dominance or when allele frequencies are equal; and (4) the broad sense heritability at full-sib or Sn family level can be used to analyze selection efficiency, since the progeny genotypic mean is, in general, a good indicator of parents, or Sn-1 plant superiority with respect to the frequency of favorable genes.

The role of P16ink4a and P53 immunostaining in predicting recurrence of HG-CIN after conization treatment

Objective: Io evaluate the expression of p16INK4a and p53 biomarkers in conization specimens from patients with high grade cervical intraepithelial neoplasia (HG-CIN), correlating them with the ability to predict the recurrence. Methods : we conducted a retrospective study of patients with HG-CIN in cervical biopsy treated with conization between January 1999 and January 2006 who had a minimum follow-up of 18 months. The expression of the p16 and p53 was assessed by tissue microarrays and correlated with disease recurrence. For analysis, we used the test of proportions (chi-square), considering value p<0.05, 95% CI and calculations of sensitivity, specificity and accuracy of these immunomarkers in predicting recurrence. Results : the series comprised 83 patients aged between 16 and 86 years (35±11.7), divided into two groups: 30 with HG-CIN recurrence (study group) and 53 without recurrence (control group). Mean age, parity, smoking and conization technique were similar in both groups. The p53 expression was present in 43% of the study group and 57% of the control group, and the p16 was present in 43% of the study group and in 57% of the control group (p>0.05). p53 had a positive predictive value (PPV) of 42% and negative predictive value (NPV) of 73%, sensitivity 70%, specificity of 47% and accuracy of 59%. The p16, PPV 42%, NPV 72%, sensitivity 66%, specificity of 49% and accuracy of 56%. Conclusion : immunohistochemistry expression of p53 and p16 showed low sensitivity and low specificity as predictors of HG-CIN recurrence after conization treatment.

Early screening for preeclampsia

Preeclampsia, which affects about 3 to 5% of pregnant women, is the most frequent medical complication in pregnancy and the most important cause of maternal and perinatal morbidity and mortality. During the past three decades, numerous clinical, biophysical, and biochemical screening tests have been proposed for the early detection of preeclampsia. Literature shows large discrepancies in the sensitivity and predictive value of several of these tests. No single screening test used for preeclampsia prediction has gained widespread acceptance into clinical practice. Instead, its value seems to be in increasing the predictive value of panels of tests, which include other clinical measurements. The aim of this review was to examine the combination of maternal risk factors, mean arterial blood pressure, and uterine artery Doppler, together with biomarkers in the preeclampsia prediction.

Uterine Doppler velocimetry of the uterine arteries in the second and third trimesters for the prediction of gestational outcome

PURPOSE: The aim of this longitudinal study was to investigate the value of uterine artery Doppler sonography during the second and third trimesters in the prediction of adverse pregnancy outcome in low-risk women. METHODS: From July 2011 to August 2012, a total of 205 singleton pregnant women presenting at our antenatal clinic were enrolled in this prospective study and were assessed for baseline demographic and obstetric data. They underwent ultrasound evaluation at the time of second and third trimesters, both included Doppler assessment of bilateral uterine arteries to determine the values of the pulsatility index (PI) and resistance index (RI) and presence of early diastolic notch. The endpoint of this study was assessing the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Doppler ultrasonography of the uterine artery, for the prediction of adverse pregnancy outcomes including preeclampsia, stillbirth, placental abruption and preterm labor. RESULTS: The mean age of cases was 26.4±5.11. The uterine artery PI and RI values for both second (PI: 1.1±0.42 versus 1.53±0.59, p=0.002; RI: 0.55±0.09 versus 0.72±0.13, p=0.000 respectively) and third-trimester (PI: 0.77±0.31 versus 1.09±0.46, p=0.000; RI: 0.46±0.10 versus 0.60±0.14, p=0.010 respectively) evaluations were significantly higher in patients with adverse pregnancy outcome than in normal women. Combination of PI and RI >95th percentile and presence of bilateral notch in second trimester get sensitivity and specificity of 36.1 and 97% respectively, while these measures were 57.5 and 98.2% in third trimester. CONCLUSIONS: According to our study, it seems that uterine artery Doppler may be a valuable tool for the prediction of a variety of adverse outcomes in second and third trimesters.

Predictive Capability of HPV and Pap Tests in Screening for Cervical Cancer over a Three-Year Follow-up

Purpose To compare the predictive capability of HPV and Pap smear tests for screening pre-cancerous lesions of the cervix over a three-year follow-up, in a population of users of the Brazilian National Health System (SUS). Methods This is a retrospective cohort study of 2,032 women with satisfactory results for Pap smear and HPV tests using second-generation hybrid capture,made in a previous study. We followed them for 36 months with data obtained from medical records, the Cervix Cancer Information System (SISCOLO), and the Mortality Information System (SIM). The outcome was a histological diagnosis of cervical intraepithelial neoplasia grade 2 or more advanced lesions (CIN2ş). We constructed progression curves of the baseline test results for the period, using the Kaplan-Meier method, and estimated sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratios for each test. Results A total of 1,440 women had at least one test during follow-up. Progression curves of the baseline test results indicated differences in capability to detect CIN2ş (p < 0.001) with significantly greater capability when both tests were abnormal, followed by only a positive HPV test. The HPV test was more sensitive than the Pap smear (88.7% and 73.6%, respectively; p < 0.05) and had a better negative likelihood ratio (0.13 and 0.30, respectively). Specificity and positive likelihood ratio of the tests were similar. Conclusions These findings corroborate the importance of HPV test as a primary cervical cancer screening.

Maternal age and Down syndrome in Southeastern Brazil

The proportion of maternal-age-independent patients estimated among 200 Brazilian Down syndrome children (59.6%) was significantly larger than that of maternal-age-dependent cases (40.4%). The latter proportion is the smallest observed in pertinent literature and due basically to the low mean maternal age of the population analyzed. Based on the remarkable correlation (r = 0.95) between the proportion of maternal-age-dependent patients and the mean maternal age of the general population, a simple predictive equation to estimate the proportion of maternal-age-dependent Down syndrome patients based on the mean maternal age of the general population is suggested in situations where reliable data on the incidence of this syndrome according to maternal age is not available.

Monitoring human cytomegalovirus viral load in peripheral blood leukocytes of renal transplant recipients by a simple limiting dilution-PCR assay

To assess the clinical relevance of a semi-quantitative measurement of human cytomegalovirus (HCMV) DNA in renal transplant recipients within the typical clinical context of a developing country where virtually 100% of both receptors and donors are seropositive for this virus, we have undertaken HCMV DNA quantification using a simple, semi-quantitative, limiting dilution polymerase chain reaction (PCR). We evaluated this assay prospectively in 52 renal transplant patients from whom a total of 495 serial blood samples were collected. The samples scored HCMV positive by qualitative PCR had the levels of HCMV DNA determined by end-point dilution-PCR. All patients were HCMV DNA positive during the monitoring period and a diagnosis of symptomatic infection was made for 4 of 52 patients. In symptomatic patients the geometric mean of the highest level of HCMV DNAemia was 152,000 copies per 106 leukocytes, while for the asymptomatic group this value was 12,050. Symptomatic patients showed high, protracted HCMV DNA levels, whereas asymptomatic patients demonstrated intermittent low or moderate levels. Using a cut-off value of 100,000 copies per 106 leukocytes, the limiting dilution assay had sensitivity of 100%, specificity of 92%, a positive predictive value of 43% and a negative predictive value of 100% for HCMV disease. In this patient group, there was universal HCMV infection but relatively infrequent symptomatic HCMV disease. The two patient groups were readily distinguished by monitoring with the limiting dilution assay, an extremely simple technology immediately applicable in any clinical laboratory with PCR capability.

Comparison of AutoSetä and polysomnography for the detection of apnea-hypopnea events

The use of the flow vs time relationship obtained with the nasal prongs of the AutoSetä (AS) system (diagnosis mode) has been proposed to detect apneas and hypopneas in patients with reasonable nasal patency. Our aim was to compare the accuracy of AS to that of a computerized polysomnographic (PSG) system. The study was conducted on 56 individuals (45 men) with clinical characteristics of obstructive sleep apnea (OSA). Their mean (± SD) age was 44.6 ± 12 years and their body mass index was 31.3 ± 7 kg/m2. Data were submitted to parametric analysis to determine the agreement between methods and the intraclass correlation coefficient was calculated. The Student t-test and Bland and Altman plots were also used. Twelve patients had an apnea-hypopnea index (AHI) <10 in bed and 20 had values >40. The mean (± SD) AHI PSG index of 37.6 (28.8) was significantly lower (P = 0.0003) than AHI AS (41.8 (25.3)), but there was a high intraclass correlation coefficient (0.93), with 0.016 variance. For a threshold of AHI of 20, AS showed 73.0% accuracy, 97% sensitivity and 60% specificity, with positive and negative predictive values of 78% and 93%, respectively. Sensitivity, specificity and negative predictive values increased in parallel to the increase in AHI threshold for detecting OSA. However, when the differences of AHI PSG-AS were plotted against their means, the limits of agreement between the methods (95% of the differences) were +13 and -22, showing the discrepancy between the AHI values obtained with PSG and AS. Finally, cubic regression analysis was used to better predict the result of AHI PSG as a function of the method proposed, i.e., AHI AS. We conclude that, despite these differences, AHI measured by AutoSetä can be useful for the assessment of patients with high pre-test clinical probability of OSA, for whom standard PSG is not possible as an initial step in diagnosis.

Hypomagnesemia in critically ill cancer patients: a prospective study of predictive factors

Hypomagnesemia is the most common electrolyte disturbance seen upon admission to the intensive care unit (ICU). Reliable predictors of its occurrence are not described. The objective of this prospective study was to determine factors predictive of hypomagnesemia upon admission to the ICU. In a single tertiary cancer center, 226 patients with different diagnoses upon entering were studied. Hypomagnesemia was defined by serum levels <1.5 mg/dl. Demographic data, type of cancer, cause of admission, previous history of arrhythmia, cardiovascular disease, renal failure, drug administration (particularly diuretics, antiarrhythmics, chemotherapy and platinum compounds), previous nutrition intake and presence of hypovolemia were recorded for each patient. Blood was collected for determination of serum magnesium, potassium, sodium, calcium, phosphorus, blood urea nitrogen and creatinine levels. Upon admission, 103 (45.6%) patients had hypomagnesemia and 123 (54.4%) had normomagnesemia. A normal dietary habit prior to ICU admission was associated with normal Mg levels (P = 0.007) and higher average levels of serum Mg (P = 0.002). Postoperative patients (N = 182) had lower levels of serum Mg (0.60 ± 0.14 mmol/l compared with 0.66 ± 0.17 mmol/l, P = 0.006). A stepwise multiple linear regression disclosed that only normal dietary habits (OR = 0.45; CI = 0.26-0.79) and the fact of being a postoperative patient (OR = 2.42; CI = 1.17-4.98) were significantly correlated with serum Mg levels (overall model probability = 0.001). These findings should be used to identify patients at risk for such disturbance, even in other critically ill populations.

Serum antigliadin antibody levels as a screening criterion before jejunal biopsy indication for celiac disease in a developing country

The objective of the present study was to determine the efficacy of detection of antigliadin immunoglobulins G and A (IgG and IgA) for the diagnosis of celiac disease in a developing country, since other enteropathies might alter the levels of these antibodies. Three groups were studied: 22 patients with celiac disease (mean age: 30.6 months), 61 patients with other enteropathies (mean age: 43.3 months), and 46 patients without enteropathies (mean age: 96.9 months). Antigliadin IgG and IgA ELISA showed sensitivity of 90.9 and 95.5%, respectively. With the hypothetical values of prevalence ranging from 1:500 to 1:2000 liveborns, the positive predictive value varied from 8.5 to 2.3% for IgG and from 4.8 to 1.1% for IgA. Considering the patients without enteropathies, specificity was 97.8 and 95.7% for IgG and IgA, respectively. In patients with other enteropathies, specificity was 82.0 and 84.1%, respectively. When patients with and without other enteropathies were considered as a whole, specificity was 88.8 and 91.6%, respectively. The specificity of positive IgG or IgA was 93.5% in children without enteropathies and 78.7% in the presence of other enteropathies. The negative predictive value for hypothetical prevalences varying from 1:500 to 1:2000 liveborns was 99.9%. Thus, even in developing countries where the prevalence of non-celiac enteropathies is high, the determination of serum antigliadin antibody levels is a useful screening test prior to the jejunal biopsy in the investigation of intestinal malabsorption.

Relationship between microalbuminuria and cardiac structural changes in mild hypertensive patients

The aim of this study was to determine the relationship between urinary albumin excretion (UAE), cardiac structural changes upon echocardiography and 24-h ambulatory blood pressure (ABPM) levels. Twenty mild hypertensive patients (mean age 56.8 ± 9.6 years) were evaluated. After 2 weeks of a washout period of all antihypertensive drugs, all patients underwent an echocardiographic evaluation, a 24-h ABPM and an overnight urine collection. Systolic and diastolic blood pressure during 24-h ABPM was 145 ± 14/91 ± 10 mmHg (daytime) and 130 ± 14/76 ± 8 mmHg (nighttime), respectively. Seven (35%) patients presented UAE > or = 15 µg/min, and for the whole group, the geometric mean value for UAE was 10.2 x/÷ 3.86 µg/min. Cardiac measurements showed mean values of interventricular septum thickness (IVS) of 11 ± 2.3 mm, left ventricular posterior wall thickness (PWT) of 10 ± 2.0 mm, left ventricular mass (LVM) of 165 ± 52 g, and left ventricular mass index (LVMI) of 99 ± 31 g/m². A forward stepwise regression model indicated that blood pressure levels did not influence UAE. Significant correlations were observed between UAE and cardiac structural parameters such as IVS (r = 0.71, P<0.001), PWT (r = 0.64, P<0.005), LVM (r = 0.65, P<0.005) and LVMI (r = 0.57, P<0.01). Compared with normoalbuminuric patients, those who had microalbuminuria presented higher values of all cardiac parameters measured. The predictive positive and negative values of UAE > or = 15 µg/min for the presence of geometric cardiac abnormalities were 75 and 91.6%. These data indicate that microalbuminuria in essential hypertension represents an early marker of cardiac structural damage.