2,134 research outputs found
Sample size for recurrent events data in non randomized studies with an historical control
No full textIn some exceptional circumstances, as in very rare diseases, non randomised trials with historical controls may be the only way to demonstrate efficacy and safety of a new treatment. The design of such studies needs a sound methodological approach in order to provide a good level of scientific evidence. To our knowledge, no attention has been given to the development of methods for sample size calculation for non randomized controlled trials (one treatment arm) where the end-point deals with recurrent events. In this context, guidelines for study design, including formulas for sample size, were only proposed for the typical scenario of randomized clinical trial (Bernardo and Harrington, 2001; Cook and Wei, 2003; Matsui, 2005). Here we propose an approach to power and sample size calculation for non randomised trials with historical controls that relies on simulation studies. Non parametric tests statistics will be considered, with the rate of events of the historical control as a reference. We will also develop an extension that accounts for paired comparisons in cases where information on pre-treatment event history of patients is available. Simulations will explore different models for the underlying event generation process (i.e. homogeneous, non homogeneous, mixed Poisson process) in order to evaluate the robustness of sample size calculation. The approach will be illustrated with a non randomized trial on experimental gene therapy in a very rare immunodeficiency (ADA-SCID), where a major end-point is the history of recurrent severe infections
Application of oligosaccharidic gold nanoparticles to the vaccines for the therapy of brest cancer: synthesis of Neu5Gc-lactose antigen starting from a complex ganglioside mixture
No full text
Analysis of recurrent complications with intermittent exposure and time-varying treatment in cancer
No full textCancer treatment usually induces a depression of the immune system, that may cause neutropenic periods in which the patient is exposed to an increased risk of infections and sever complications, typically announced by fever (common symptom). A prospective observational study conducted between 2002 and 2004 at the Gaslini Hospital in Italy gathered information on neutropenic periods of 157 children affected by different types of solid tumours, receiving chemotherapy regimens (classified into two broad categories, very intensive and intensive) and, possibly, autologous hemopoietic stem cell transplantation. The aim was to asses the role of treatment in the incidence of recurrent febrile complications during neutropenic periods, accounting for the history of past events, the intermittence of exposure and the time-varying nature of treatment.
We considered a stratified Cox model for a marginal and frailty analysis, stratified by type of cancer, with age and sex as fixed covariates and treatment as a time-dependent covariate. The results suggested that patients who underwent transplantation were more likely to develop febrile episodes. Unmeasured heterogeneity between patients did not appear to be relevant and results of the frailty model were very similar to that of the marginal model. The need to evaluate how the history of previous febrile episodes impacts on the current risk of developing fever requires further developments. In particular, the approach explored in this regard is the Aalen’s Additive Hazard model, that may be useful to disentangle the role of treatment and the influence of previous events
Ceramides as possible nutraceutical compounds : characterization of the ceramides of the moro blood orange (citrus sinensis)
No full textCeramides are presented as nutraceutical compounds for protection of colon carcinoma and as important
cosmetic preparation components, increasing absorption through the skin. Therefore, the ceramide (Cer) content of Moro blood
oranges was determined by mass spectrometry. A total of 114 Cer species were identified: ∼160 mg in the peels and ∼140 mg in
the pulp per kilogram of oranges, expressed as “milligram equivalents of d18:1,17:0 Cer”. The predominant ceramides contained
4-hydroxy-8-sphingenine (t18:1Δ8) and 4-hydroxysphinganine (t18:0) as long-chain bases (LCBs) and fatty acids (FAs) with
different structures. In the pulp, t18:1Δ8- and t18:0-containing Cer species comprised 50.5 and 33.5% of the total, respectively,
11.5 and 3.5% non-hydroxylated FAs, respectively, 32.0 and 21.0% α-hydroxylated FAs, respectively, and 7.0 and 9.0% α,β-
hydroxylated FAs, respectively. In the peels, t18:1Δ8- and t18:0-containing species comprised 49.5 and 34.5% of the total,
respectively, 16.0 and 1.5% non-hydroxylated FAs, respectively, 31.5 and 29.0% α-hydroxylated FAs, respectively, and 2.0 and
4.0% α,β-hydroxylated FAs, respectively
Exploratory Data Analysis of Multiway Contingency Tables. A Regression Diagnostics Approach
No full textDante poeta-profeta, pellegrino, autore : strutturazione espessiva della Commedia e visione escatologica dantesca
No full textLo studio del profetismo dantesco e del rapporto tra esso e la "lupa" (cioè la cupidigia-volontà di potenza, è condotto attraverso l'analisi dei momenti più intensamente profetici del poema: dagli aspetti escatologici, politici e sociali dell'antefatto, attraverso le intense reminiscenze da Ezechiele e da Apocalisse ricontestualizzate in Purg. XIX e XX, alle grandiose visioni escatologico-politiche di Purg. XXXII e XXXIII, alla sommessa e dolente speranza espressa negli ultimi canti di Beatrice.Il grido profetico di Dante è inseparabile dalle diverse immagini del poeta all'interno della Commedia: il poeta-pellegrino (l'agens); il poeta-scriba, addetto a riprodurre le esperienze vissute dal pellegrino; l'autore, cioè il poeta-profeta, il quale dice "io" anch'egli e intervienedal presente della scrittura per ammaestrare il lettore ed esecrare i vizi della cristianità sviata. Si esamina quindi la posizione di Dante tra i poeti-auctores antichi e l'auctoritas che spetta ai libri sacri di AT e di NT.The study of Dantean prophetism and of its relationship with the “she-wolf” (that is greed-lust for power), is carried out through the analysis of the most intensely prophetic moments of the poem: from the eschatological, political and social aspects of the background, through the intense reminiscences from Ezekiel and Apocalypse re-contextualized in Purgatory XIX and XX, to the great eschatological-political visions of Purgatory XXXII and XXXIII, to the quiet and sorrowful hope expressed in Beatrice's last cantos. Dante's prophetic cry is inseparable from the different images of the poet inside the Comedy : the pilgrim poet (the agens); the scribe poet, assigned to reproduce the experiences lived by the pilgrim; the author, that is the prophet poet, who also says “I” and intervenes from the present of the writing to teach the reader and execrate the vices of led astray Christianity. Then Dante's position is examined between the ancient auctores- poets and the auctoritas due to the holy books of the Old and New Testament
Identification of the fenretinide metabolite 4-oxo-fenretinide present in human plasma and formed in human hovarian carcinoma cells throught induction of cytochrome PA450 26A1
No full textPURPOSE: The synthetic retinoid fenretinide (4-HPR) exhibits preventive and therapeutic activity against ovarian tumors. An unidentified polar metabolite was previously found in 4-HPR-treated subjects and in A2780 human ovarian carcinoma cells continuously treated with 4-HPR (A2780/HPR). The metabolite and the enzyme involved in its formation in tumor cells are herein identified. EXPERIMENTAL DESIGN: The metabolite was identified by mass spectrometry in A2780/HPR cell extracts and in plasma from 11 women participating in a phase III trial and treated with 200 mg/d 4-HPR for 5 years. The expression of proteins involved in retinoid metabolism and transport, cytochrome P450 26A1 (CYP26A1), cellular retinol-binding protein I (CRBP-I), and cellular retinoic acid-binding protein I and II (CRABP-I, CRABP-II) were evaluated in tumor cells by reverse transcription-PCR and Western blot analyses. Overexpression of CYP26A1 and retinoic acid receptors (RARs) in A2780 cells were obtained by cDNAs transfection. RESULTS: The polar metabolite was 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR) i.e., an oxidized form of 4-HPR with modification in position 4 of the cyclohexene ring. 4-oxo-4-HPR plasma levels were slightly lower (0.52 +/- 0.17 micromol/L) than those of the parent drug (0.84 +/- 0.53 micromol/L) and of the already identified metabolite N-(4-methoxyphenyl)retinamide (1.13 +/- 0.85 micromol/L). In A2780/HPR cells continuously treated with 4-HPR and producing 4-oxo-4-HPR, CYP26A1 and CRBP-I were markedly up-regulated compared with A2780 untreated cells. In A2780 cells, not producing 4-oxo-4-HPR, overexpression of CYP26A1 caused formation of 4-oxo-4-HPR, which was associated with no change in 4-HPR sensitivity. Moreover, the addition of 4-oxo-4-HPR to A2780 cells inhibited cell proliferation. Elevated levels of CYP26A1 protein and metabolism of 4-HPR to 4-oxo-4-HPR were found in A2780 cells transfected with RARbeta and to a lesser extent in those transfected with RARgamma. CONCLUSIONS: A new metabolite of 4-HPR, 4-oxo-4-HPR, present in human plasma and in tumor cells, has been identified. The formation of this biologically active metabolite in tumor cells was due to CYP26A1 induction and was influenced by RAR expression. Moreover evidence was provided that 4-HPR up-modulates the expression of CRBP-I transcript, which is lost during ovarian carcinogenesis
Sant'Ambrogio nella letteratura religiosa slava orientale del Sei e Settecento : per uno studio preliminare delle citazioni ambrosiane nell'omiletica rutena barocca
No full textThe aim of this study is to investigate the reception of Ambrose in the writings of three Ukrainian baroque preachers, viz. Ioannikij Galjatovs’kyj, Antonij Radyvylovs’kyj and Dimitrij Rostovskij. The method that has been adopted in the presentation of the results of our survey can be outlined as follows. First, we focused on the thematic aspects of the process of reception, which generally fall into two categories: 1. Exegetical themes, based on motives drawn from the Scriptures; 2. Philosophical-doctrinal themes. Furthermore, for all the writers which we examined we tried to determine whether an author made a direct or indirect usage of Ambrose’s oeuvre. Indirect use is generally to be ascribed to the influence of either exegetic Comments on the Bible, such as those of Cornelius A Lapide and Didacus de Baeza, or of emblematic literature produced in the West, such as Hemannus Hugo’s Pia desideria (1624).
A second question to be addressed is how the intellectual and ecclesiastical context of the Ukrainian lands, whose distinctive features were pluriconfessionalism and the close ties to Western Renaissance and Baroque, influenced our authors in the way they made use of Ambrose, especially as far as the relationship between Orthodoxy and Catholicism is concerned
Cardiovascular risk assessment in children : role of physical activity, family history and parental smoking on BMI and blood pressure
No full textOBJECTIVE: Aim of the study was to assess the role of family history, physical activity and parental smoking in the prediction of BMI, SBP and hypertension risk in children. PARTICIPANTS AND METHODS: In a paediatric primary care setting, a sample of 1310 children aged 5-14 years was systematically selected by 48 family paediatricians in northern Italy. BMI, waist circumference-to-height ratio (WtHr), SBP and DBP were measured and the information on the presence of small birth weight for gestational age (SGA) and early adiposity rebound (EAR) was collected. Data concerning exercise, video time, family history for cardiovascular diseases and parental smoking were derived from parental interview. Data were collected using an 'ad hoc designed' electronic sheet available online. RESULTS: Multiple linear regression showed that the presence of EAR, low exercise (2 h/day TV/videogames/computer) and parental smoking were associated to higher BMI (z-score; P < 0.005). Age, BMI (z-score), WtHr, presence of SGA, low exercise, high video time and family history of cardiovascular diseases were associated to SBP values (P < 0.03). Logistic regression analysis showed that factors related to risk of hypertension and prehypertension were BMI (z-score; odds ratio, OR 2.63; 95% confidence interval, CI 2.12-3.28), WtHr (OR 1.13; 95% CI 1.10-3.28) and low exercise (OR 1.58; 95% CI 1.12-2.24; P <0.01). CONCLUSION: Our study demonstrates that a simple tool like a cardiovascular multi-item sheet can provide useful information to paediatricians for child health. Physical exercise plays a pivotal role in obesity prevention and protection from hypertension risk
- …
