Joint analysis of longitudinal and survival AIDS data with a spatial fraction of long-term survivors: A Bayesian approach.

A typical survival analysis with time-dependent covariates usually does not take into account the possible random fluctuations or the contamination by measurement errors of the variables. Ignoring these sources of randomness may cause bias in the estimates of the model parameters. One possible way for overcoming that limitation is to consider a longitudinal model for the time-varying covariates jointly with a survival model for the time to the event of interest, thereby taking advantage of the complementary information flowing between these two-model outcomes. We employ here a Bayesian hierarchical approach to jointly model spatial-clustered survival data with a fraction of long-term survivors along with the repeated measurements of CD4+ T lymphocyte counts for a random sample of 500 HIV/AIDS individuals collected in all the 27 states of Brazil during the period 2002-2006. The proposed Bayesian joint model comprises two parts: on the one hand, a flexible model using Penalized Splines to better capture the nonlinear behavior of the different CD4 profiles over time; on the other hand, a spatial cure model to cope with the set of long-term survivor individuals. Our findings show that joint models considering this set of patients were the ones with the best performance comparatively to the more traditional survival approach. Moreover, the use of spatial frailties allowed us to map the heterogeneity in the disease risk among the Brazilian states.

Bayesian joint modeling of longitudinal and spatial survival AIDS data.

Joint analysis of longitudinal and survival data has received increasing attention in the recent years, especially for analyzing cancer and AIDS data. As both repeated measurements (longitudinal) and time-to-event (survival) outcomes are observed in an individual, a joint modeling is more appropriate because it takes into account the dependence between the two types of responses, which are often analyzed separately. We propose a Bayesian hierarchical model for jointly modeling longitudinal and survival data considering functional time and spatial frailty effects, respectively. That is, the proposed model deals with non-linear longitudinal effects and spatial survival effects accounting for the unobserved heterogeneity among individuals living in the same region. This joint approach is applied to a cohort study of patients with HIV/AIDS in Brazil during the years 2002-2006. Our Bayesian joint model presents considerable improvements in the estimation of survival times of the Brazilian HIV/AIDS patients when compared with those obtained through a separate survival model and shows that the spatial risk of death is the same across the different Brazilian states. Copyright © 2016 John Wiley & Sons, Ltd.

DNA ploidy is an independent predictor of survival in breast invasive ductal carcinoma: a long-term multivariate analysis of 393 patients.

PURPOSE: To evaluate "classic" prognostic parameters, as well as DNA ploidy and S-phase fraction (SPF), in relation to disease-free (DFS) and disease-specific (DSS) survival in breast invasive ductal carcinoma (IDC) with long-term follow-up study. METHODS: The study involved 393 patients with IDC and median follow-up of 134 months (50-240). Histological grading, tumor size, axillary nodal involvement, pathological staging and hormone receptor status were considered as established prognostic markers. Ploidy and SPF were determined prospectively by DNA flow cytometry using fresh/frozen tissue. A Cox regression model was used for statistical analysis of the prognostic variables. RESULTS: There were 105 (26.7 %) deaths and 140 (35.6 %) disease recurrences during follow-up. Two hundred thirty-one (58.8 %) tumors were aneuploid. High SPF and aneuploidy were associated with tumors with higher grade of differentiation, greater size and negative hormone receptors. Higher SPF and advanced disease stage are correlated. In univariate analysis, all the clinicopathological and cytometric features, including patients <40 years and a subgroup presenting hypertetraploid/multiploid tumors, are significantly correlated with clinical outcome, apart from SPF and estrogen receptors for DFS. In multivariate analysis, nodal involvement, DNA aneuploidy and lack of progesterone receptors (for DSS) retained statistically significant association with shorter survival. In node-negative patients, ploidy (for DFS) and estrogen receptors (for DSS) significantly predicted survival. In both subgroups of node-positive patients and those (n = 195) with intermediate differentiation tumors (G2), aneuploidy was an indicator of worse prognosis. CONCLUSIONS: Along with nodal status and hormone receptor expression, DNA ploidy is an independent predictor of long-term survival in IDC.

DNA aneuploidy identifies a subset of Luminal subtype breast carcinoma patients with worse clinical outcome.

AIM: In breast carcinoma (BC), the relationship between the ploidy pattern and molecular subtyping is still unknown. We aim to investigate the prognostic impact of DNA ploidy within molecular subtypes of a large cohort of BC patients. METHODS: The series involved 520 BC patients with no neoadjuvant therapy and a median follow-up of 115.5 months. Immunohistochemical assessment of hormonal receptors, ERBB2 (HER2) status and Ki67 proliferative activity was the basis of the surrogate molecular subtyping. Ploidy was evaluated by DNA flow cytometry in fresh/frozen tumour samples. Kaplan-Meier (K-M) survival estimation was used for prognostic statistical analysis. RESULTS: Luminal A subtype had the lowest prevalence of disease recurrences (23.6 %) and deaths from disease (18.3 %), while Luminal B (42.2 %/37.9 %), Triple-negative (46.4 %/40.6 %), and HER2-positive (55.9 %/50.0 %) subtypes had the highest. The Triple-positive subtype shows an intermediate/low frequency of adverse events (29.4 % of disease recurrences and 17.6 % of deaths from disease). Luminal A tumours were mostly diploid (55.3 %), while Triple-negative and HER2-positive tumours showed a high incidence of aneuploidy (82.6 % and 88.2 %, respectively). Luminal B and Triple-positive tumours had an intermediate percentage of aneuploidy (63.8 % and 70.6 %, respectively). K-M survival curves showed that DNA aneuploidy is significantly associated with shorter disease-free survival and overall survival in Luminal A and Luminal B molecular subtypes. CONCLUSION: DNA aneuploidy identifies a subset of Luminal BC patients with worse clinical outcome, potentially eligible for more aggressive adjuvant therapy.

S-phase fraction and ploidy as predictive markers in primary disease and recurrence of papillary thyroid carcinoma.

OBJECTIVE: To investigate the prognostic influence of DNA ploidy and S-phase fraction (SPF) on disease-free (DFS) and overall survival (OS) of patients with primary disease and loco-regional lymph node recurrence of papillary thyroid carcinoma (PTC). DESIGN: A large prospective study with long-term follow-up (median, 117 months). PATIENTS: Two series of patients with primary PTC (n = 305) and lymph node recurrence metastasis (LNM) (n = 39) were involved in the study. MEASUREMENTS: Patient's age and gender, histological variant, pathological tumour-node-metastasis (pTNM) staging, extrathyroidal extension, vascular and lymphatic invasion and tumour bilateral growth were the clinical and pathological characteristics evaluated. DNA flow cytometry was performed on fresh/frozen surgical tumour samples. Cox regression models were estimated for prognostic analyses. RESULTS: Seventeen (5·6%) primary tumours and five (12·8%) LNMs were aneuploid, while mean SPF was 2·7% and 3·7%, respectively (P = 0·022). High SPF was significantly associated with lymphatic invasion and tall cell and diffuse sclerosing variants. In univariate analysis, all the clinico-pathological variables, but tumour bilateral growth and gender, were significantly correlated with survival. SPF showed borderline significance (P = 0·051) in relation to OS. In multivariate analysis, older age (≥48 years), lymph node spread and high SPF were significantly adverse prognostic factors. Extrathyroidal extension and distant metastasis for OS, as well as tumour size for DFS, were also found as unfavourable prognostic features. In LNM, the Kaplan-Meier curves showed significant differences for older age and DNA aneuploidy (recurrence; P = 0·011). CONCLUSION: The results indicate that SPF and ploidy can provide additional predictive information in patients with PTC.

S-phase fraction, lymph node status and disease staging as the main prognostic factors to differentiate between young and older patients with invasive breast carcinoma.

The influence of age on the outcome of patients with invasive breast carcinoma (IBC) has not yet been fully established. The present study investigated two subgroups of patients either side of the age spectrum, and evaluated cytometric, histopathological and molecular characteristics. The series involved 219 patients with IBC that had long-term follow-up, which were divided into two subgroups: Young (≤45 years; n=103) and old patients (≥75 years; n=116). Immunohistochemical evaluation of hormonal receptors, Ki67 index and HER2 status (plus HER2 silver in situ hybridization in equivocal cases) were used as the basis for surrogate molecular subtyping. Ploidy and S-phase fraction (SPF) were analysed by DNA flow cytometry. Differences between the subgroups' characteristics were assessed by the two proportion Z test. Kaplan-Meier estimation and log-rank test were applied for survival analyses. The median age in the subgroups were 40 years (range, 19-45 years) in the young group and 78 years (range, 75-91 years) in the older subgroup. Young patients exhibited higher lymph node involvement, more advanced disease staging, higher SPF tumour proliferative activity, and a trend of lower incidence of Luminal A and higher incidence of Luminal B tumours. The median SPF value was significantly higher in young patients [7.1% (range, 1.5-23.7%) vs. 4.5% (range, 0.7-26.4%)], whereas the ploidy pattern showed no significant difference. In the whole series, as within IBC of no special type, young patients had a higher rate of recurrence (46.6 vs. 22.4%; P<0.001) and deaths from disease (35.9 vs. 20.7%; P=0.030), with a statistically significant difference for disease-free survival. In conclusion, the present study indicated that young patients with IBC exhibited more aggressive disease, with an increased risk of recurrence and shorter disease-free survival. SPF, lymph node status and staging appeared to be the main prognostic factors to differentiate young from older patients with IBC.

Wasting, Stunting, and Anemia in Angolan Children after Deworming with Albendazole or a Test-and-Treat Approach for Intestinal Parasites: Binary Longitudinal Models with Temporal Structure in a Four-Arm Randomized Trial.

Undernutrition, anemia, and intestinal parasitic infections are public health problems in Angola, especially in pre-school children. We analyzed binary data from a longitudinal four-arm randomized parallel trial conducted in Bengo Province, northern Angola, over the course of two years, with seven follow-up assessments to explore the effects of four interventions (deworming and a test-and-treat approach for intestinal parasites, at both the individual and household levels) on wasting and stunting, and to understand their indirect benefits for anemia, malaria, diarrhea, and vomiting. A total of 121 children with intestinal parasitic infections received baseline treatment, and were allocated to the four arms (1:1:1:1). Using continuous outcome variables of height-for-age (HAZ) and weight-for-height (WHZ) statistical approaches did not reveal a clear benefit of any particular arm (Pathogens 2021, 10, 309). Next, HAZ and WHZ were transformed into binary variables of stunting and wasting, respectively, considering their mild-to-severe (Z-score < −1) and moderate-to-severe degrees (Z-score < −2). Original clinical data (on anemia, diarrhea, vomiting, and malaria) were also analyzed. From a binary longitudinal analysis with different dependence structures, using the R package bild, fitted models revealed the potential benefit of a test-and-treat approach at the individual level for wasting compared with annual albendazole at the individual level, especially considering mild-to-severe forms (ORadj = 0.27; p = 0.007). All arms showed similar effects on stunting, compared with annual albendazole, at a 5% significance level. Time and age at baseline presented favorable effects in the percentage of stunting using both severity degrees. Results showed a decreased chance of having anemia and diarrhea over time, although with no significant differences between arms. Data from longitudinal studies are essential to study the direct and indirect effects of interventions, such as deworming, and to explore additional approaches aiming at better understanding the temporal structure of nutrition and health outcomes in children.

Male Breast Cancer-Immunohistochemical Patterns and Clinical Relevance of FASN, ATF3, and Collagen IV.

BACKGROUND: Male breast carcinoma (male BC) is an uncommon neoplasia without individualized strategies for diagnosis and therapeutics. Low overall survival (OS) rates have been reported, mostly associated with patients' advanced stage and older age. Intratumoral heterogeneity versus homogeneity of malignant epithelial cells seems to be an important factor to consider for the development of combination therapies with curative intention. OBJECTIVE: In this preliminary study, we aim to provide valuable insight into the distinct clinicopathologic features of male BC. MATERIAL AND METHODS: In a series of 40 male BC patients, we evaluated by immunohistochemistry androgen receptor; activating transcription factor 3 (ATF3); p16; cyclin D1; fatty acid synthase (FASN); fatty acid transport protein 1 (FATP1); ß1, ß3, ß4, and ß6 integrins; collagen I and collagen IV; and their interactions. Kaplan-Meier survival curves and log-rank tests were assessed for statistical analysis. RESULTS: Homogeneous epithelial staining of p16, ATF3, ß6 integrin, FASN, and FATP1 was found to be significantly intercorrelated, and associated with high Ki67. These markers also stained tumor stromal fibroblasts. The prognostic analysis showed statistically significant associations of FASN with disease-free survival (DFS) and OS, as well as of ATF3 with OS and collagen IV with DFS. CONCLUSIONS: This study highlights, as a novel finding, the relevance of FASN, ATF3, and collagen IV immunophenotypes, which may have innovative application in the clinical management of male BC.

Random changepoint segmented regression with smooth transition.

We consider random changepoint segmented regression models to analyse data from a study conducted to verify whether treatment with stem cells may delay the onset of a symptom of amyotrophic lateral sclerosis in genetically modified mice. The proposed models capture the biological aspects of the data, accommodating a smooth transition between the periods with and without symptoms. An additional changepoint is considered to avoid negative predicted responses. Given the nonlinear nature of the model, we propose an algorithm to estimate the fixed parameters and to predict the random effects by fitting linear mixed models iteratively via standard software. We compare the variances obtained in the final step with bootstrapped and robust ones.

Suicide and apparent temperature in the two capitals cities in the iberian peninsula.

Different authors have identified geographic variations in the rates of suicide. This study aims to discuss the limitations of the officially recorded suicide data and to evaluate the statistical relationship between a biometeorological index, Apparent Temperature (AT), and suicide in Madrid and Lisbon. We performed a time-series study. The association was analyzed using a quasi-Poisson regression model. To assess potential delayed and non-linear effects of AT on suicides, a lag non-linear model was fitted in a generalized additive model. There was an average rate of 3.30 suicides/100,000 inhabitants in Madrid and of 7.92 suicides/100,000 inhabitants in Lisbon, and a downward trend was found throughout the period. In Madrid, there is no statistically significant association between AT and suicide. However, in Lisbon, under higher AT, there was a higher risk of suicide. The highest accumulated statistically significant Relative Risk (RR) of suicide was detected at 7 days after the exposure, when at 38 °C, the risk of suicide is 2.7 times that existing at the median AT, 20.62°. The average mortality rate recorded in Lisbon was 41.6% higher than that registered in Madrid. However, the limitations of suicide record databases in Spain and Portugal have to be taken into account when analyzing incidence and especially when comparing data from different countries. It is necessary to improve the filing systems of violent deaths in order to perform reliable epidemiological studies.

Male breast cancer: Specific biological characteristics and survival in a Portuguese cohort.

Male breast cancer (BC) represents an individual subtype of BC, with therapeutic procedures based on female BC therapy results. The present study evaluated the parameters currently used for the characterization and therapy of male BC, and their association with disease-free (DFS) and overall survival (OS), aiming to obtain a comprehensive basis to improve the personalized care of male BC. A total of 196 patients from March 1970 to March 2018 (mean follow-up, 84.9 months) were profiled, using clinicopathological review, molecular assessment [BRCA1/2, DNA repair associated (BRCA1/2) status, immunohistochemistry, fluorescence in situ hybridization and DNA flow cytometry] and Cox regression statistical analysis. The median age of patients was 66.5 years. At presentation, 39.2% of patients with invasive carcinomas were in anatomic stage (AS) I. Patients exhibited primarily invasive carcinomas of no special type, histological grade 2, estrogen receptor α-(ERα) and progesterone receptor (PR)-positive, receptor tyrosine kinase erbB-2-negative, high Ki-67, Luminal B-like and aneuploid tumors. A total of 13 of the 44 (29.5%) BRCA-evaluated patients exhibited BRCA2 mutations, significantly associated with family history (FH), bilaterality, high Ki-67 expression, absence of PR and Luminal B-like tumors. Bilaterality was associated with the occurrence of non-breast primary neoplasms (NBPN). The 5 and 10-year DFS rates, excluding patients with distant metastasis, NBPN and in situ carcinomas (n=145) were 65.9 and 58.2%, respectively, and the 5 and 10-year OS rates were 77.5 and 59.2%, respectively. In the univariate analysis, Luminal B-like subtype, BRCA2 mutations, high Ki-67 expression, and AS II and III were significantly associated with shorter DFS and OS. In addition, age >70 years was associated with low OS. In the multivariate analysis, FH, AS II and III, and Luminal B-like subtypes were associated with poorer OS. In conclusion, the data from the present study emphasize the high incidence of BRCA2 mutation in male BC, and its association with FH, bilaterality, high Ki-67 expression, negative PR expression and Luminal B-like subtypes, and with shorter DFS and OS in univariate analysis.

Prognostic relevance of DNA flow cytometry in breast cancer revisited: The 25-year experience of the Portuguese Institute of Oncology of Lisbon.

The potential prognostic significance of DNA flow cytometric measurements (DNA ploidy and S-phase fraction) in breast cancer remains in dispute. Inconclusive data, primarily due to the lack of consistent standardization and quality control programs, have limited its translation into clinical practice. The aim of the present review, based on the 25-year experience of the Portuguese Institute of Oncology of Lisbon, is to assess the clinical relevance and application of DNA flow cytometry for the prognosis of breast cancer. Overall, data from Portuguese Institute of Oncology of Lisbon indicate that DNA flow cytometry provides significant prognostic information that is biologically relevant and clinically useful for the management of patients with breast cancer. Furthermore, this data has demonstrated the independent value of DNA aneuploidy as a prognostic indicator of poor clinical outcome in various subgroups of patients with early or locally advanced breast cancer at short- and long-term follow-up. Notably, aneuploidy identifies subsets of patients with grade (G)1 or G2 tumours who exhibit a poor clinical outcome. These patients may benefit from adjuvant chemotherapy, particularly those with luminal A and luminal B/human epidermal growth factor-2-negative endocrine-responsive breast cancer. In conclusion, data from Portuguese Institute of Oncology of Lisbon reinforces the clinical importance and utility of DNA flow cytometric analysis, particularly DNA ploidy, in the prognostic assessment and therapeutic planning for patients with breast cancer.

Aneuploidy identifies subsets of patients with poor clinical outcome in grade 1 and grade 2 breast cancer.

OBJECTIVE: Histological grade is a well-established prognostic/predictive factor in breast cancer. However, mainly within intermediate categories, patients may have unpredictable outcome. We hypothesised whether ploidy status can distinguish different prognostic groups among breast cancer patients with similar tumour grade. MATERIAL AND METHODS: The study involved 684 patients with invasive breast carcinoma, and median follow-up of 134.5 months. Pathological staging was evaluated according to WHO classification. Tumour differentiation was assessed using the Nottingham grading system. Ploidy was determined prospectively by DNA flow cytometry. Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method. RESULTS: There were 179 (26.2%) deaths and 239 (33.3%) disease recurrences. For grading, tumours were classified as follows: 163 (23.8%) G1, 356 (52.1%) G2 and 165 (24.1%) G3, while 389 (56.9%) tumours presented aneuploidy. Ploidy and grading are strongly associated (P < 0.001). Patients with aneuploid G2 tumours showed worse DFS (P = 0.001) and OS (P < 0.001), as well as those with aneuploid G1 tumours in relation to OS (P = 0.013). When a subset analysis was performed in early breast cancer patients (n = 451) with Stage I/IIA of disease, it remained the same significant associations of aneuploid G1 (to OS) and G2 tumours (to DFS and OS) with unfavourable prognosis. CONCLUSIONS: Aneuploidy identifies subsets of breast cancer patients with G1 and G2 tumours who showed poor clinical outcome. The finding has therapeutic implications, as these patients are potential candidates to risk-adapted adjuvant therapy.

Familial vs sporadic papillary thyroid carcinoma: a matched-case comparative study showing similar clinical/prognostic behaviour.

OBJECTIVE: Familial non-medullary thyroid cancer has been proposed as an aggressive clinical entity. Our aim in this study is to investigate potential distinguishing features as well as the biological and clinical aggressiveness of familial vs sporadic papillary thyroid carcinoma (PTC). We assessed clinicopathological characteristics, outcome measures and DNA ploidy. DESIGN: A matched-case comparative study. METHODS: A series of patients with familial PTC (n=107) and two subgroups, one with three or more affected elements (n=32) and another including index cases only (n=61), were compared with patients with sporadic PTC (n=107), matched by age, gender, pTNM disease extension and approximate follow-up duration. Histological variant, extrathyroidal extension, vascular invasion, tumour multifocality and bilateral growth were evaluated. Ploidy pattern was analysed in available samples by DNA flow cytometry. The probabilities of disease-free survival (DFS) and overall survival (OS) were estimated according to the Kaplan-Meier (K-M) method. RESULTS: No patient with familial PTC died of disease during follow-up (median, 72 months), contrarily to five patients (4.7%) (P=0.06) with sporadic PTC (median, 90 months). There was a significantly higher tumour multifocality in familial PTC (index cases subgroup) vs sporadic PTC (P=0.035), and a trend, in the familial PTC cohort with three or more affected elements, to show extrathyroidal extension (P=0.054) more frequently. No difference was observed in DNA ploidy status. The K-M analyses showed no significant differences between both entities in relation to DFS or OS. CONCLUSION: Apart from multifocality, familial PTC appears to have similar clinical/prognostic behaviour when compared with sporadic forms of the disease.

The impact of winter cold weather on acute myocardial infarctions in Portugal.

Mortality due to cardiovascular diseases shows a seasonal trend that can be associated with cold weather. Portugal is the European country with the highest excess winter mortality, but nevertheless, the relationship between cold weather and health is yet to be assessed. The main aim of this study is to identify the contribution of cold weather to cardiovascular diseases within Portugal. Poisson regression analysis based on generalized additive models was applied to estimate the influence of a human-biometeorological index (PET) on daily hospitalizations for myocardial infarction. The main results revealed a negative effect of cold weather on acute myocardial infarctions in Portugal. For every degree fall in PET during winter, there was an increase of up to 2.2% (95% CI = 0.9%; 3.3%) in daily hospital admissions. This paper shows the need for public policies that will help minimize or, indeed, prevent exposure to cold.

Clinical relevance of the reappraisal of negative hormone receptor expression in breast cancer.

BACKGROUND: Accurate assessment of estrogen (ER) and progesterone (PR) receptors is critical in predicting the response to endocrine therapies in breast cancer. MATERIAL AND METHODS: From a series of 360 patients with breast invasive carcinoma assessed for hormone receptors by immunohistochemistry (IHC) in the 90's, we re-analysed, on the same tumour material, the cases considered negative (n = 164), i.e., ER-/PR- (n = 95), ER+/PR- (n = 63) and ER-/PR+ (n=6), and 16 of 196 ER+/PR+ tumours with unfavourable outcome. Concordance between the previous IHC (Streptavidin-Biotin-Peroxidase) method and the current one (Peroxidase-Indirect-Polymer) was determined by the McNemar's test. Relapse-free (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method. RESULTS: From 101 ER- and 158 PR- cases, 38 (37.6%) and 58 (36.7%) became positive, increasing ER and PR expression from 71.9% and 56.1% to 82.5% and 72.2%, respectively (P<0.001). All 16 ER+/PR+ cases maintained their co-positivity, while all ER-/PR+ tumours changed to ER positive. Kaplan-Meier survival curves showed significant differences related to RFS and OS for PR, either in the whole series or in the subset (n = 151) submitted to hormonal treatment. The patients' subgroup with ER+/PR- tumours exhibited the worst prognosis. CONCLUSION: The current IHC method improves the clinical usefulness of ER/PR assessment by decreasing the rate of false negative results.

[DNA ploidy is an independent prognostic biomarker in breast invasive ductal carcinoma]. / A ploidia de ADN é um biomarcador prognóstico independente no carcinoma ductal invasivo da mama.

OBJECTIVE: To evaluate 'classic' prognostic parameters, as well as DNA ploidy and S-phase fraction, in relation to disease-free and overall survival in breast invasive ductal carcinoma with long-term follow-up. MATERIAL AND METHODS: The study involved 400 patients with breast invasive ductal carcinoma and median follow-up of 134 months (50-240). Histological grading, tumour size, axillary nodal involvement, pathological staging and hormone-receptor status were assessed as established prognostic markers. Ploidy and S-phase fraction were determined prospectively by DNA flow cytometry using fresh/frozen tissue. A Cox regression model was used for statistical analysis of the prognostic variables. RESULTS: There were 106 deaths (26.5%) and 141 disease recurrences (35.2%) during follow-up. Two hundred thirty-five (58.7%) tumours were aneuploid. High S-phase fraction and aneuploidy were associated with tumours with higher grade of differentiation, greater size and negative hormonal receptors. In univariate analysis, all the clinicopathological and cytometric features (including patients < 40 years and a subgroup presenting hipertetraploid/multiploid tumours), but S-phase fraction and estrogen receptors for disease free survival, significantly correlated with clinical outcome. In multivariate analysis, advanced disease stage, DNA aneuploidy and lack of progesterone receptors retained statistically significant association with shorter survival. In the subgroup of patients with intermediate differentiation tumours (G2), aneuploidy associated with worse prognosis. In the subset of node-negative patients, only estrogen receptors showed significant correlation with disease evolution. In node-positive patients, greater size tumours and aneuploidy (in relation to overall survival) were indicators of worse prognosis. CONCLUSION: Along with disease staging and hormone-receptor expression, DNA ploidy is an independent prognostic biomarker of long-term survival in breast invasive ductal carcinoma.

Hierarchical Bayesian spatiotemporal analysis of revascularization odds using smoothing splines.

Hierarchical Bayesian models are proposed for over-dispersed longitudinal spatially correlated binomial data. This class of models accounts for correlation among regions by using random effects and allows a flexible modelling of spatiotemporal odds by using smoothing splines. The aim is (i) to develop models which will identify temporal trends of odds and produce smoothed maps including regional effects, (ii) to specify Markov chain Monte Carlo (MCMC) inference for fitting such models, (iii) to study the sensitivity of such Bayesian binomial spline spatiotemporal analyses to prior assumptions, and (iv) to compare mechanisms for assessing goodness of fit. An analysis of regional variation for revascularization odds of patients hospitalized for acute coronary syndrome in Quebec motivates and illustrates the methods developed.