Role of brachytherapy in the treatment of cancers of the anal canal. Long-term follow-up and multivariate analysis of a large monocentric retrospective series.

BACKGROUND AND PURPOSE: There are few data on long-term clinical results and tolerance of brachytherapy in anal canal cancer. We present one of the largest retrospective analyses of anal canal cancers treated with external beam radiotherapy with/without (±) chemotherapy followed by a brachytherapy boost. MATERIALS AND METHODS: We performed a retrospective analysis of clinical results in terms of efficacy and toxicity. The impact of different clinical and therapeutic variables on these outcomes was studied. RESULTS: From May 1992 to December 2009, 209 patients received brachytherapy after external beam radiotherapy ± chemotherapy. Of these patients, 163 were stage II or stage IIIA (UICC 2002) and 58 were N1-3. According to age, ECOG performance status (PS), and comorbidities, patients received either radiotherapy alone (58/209) or radiochemotherapy (151/209). The median follow-up was 72.8 months. The 5- and 10-year local control rates were 78.6 and 73.9 %, respectively. Globally, severe acute and late G3-4 reactions (NCI-CTC scale v. 4.0) occurred in 11.2 and 6.3 % of patients, respectively. Univariate analysis showed the statistical impact of the pelvic treatment volume (p = 0.046) and of the total dose (p = 0.02) on the risk of severe acute and late toxicities, respectively. Only six patients required permanent colostomy because of severe late anorectal toxicities. CONCLUSION: After a long follow-up time, brachytherapy showed an acceptable toxicity profile and high local control rates in patients with anal canal cancer.

The Impact of EU Membership on the Economic Governance of Spain

[spa] España no fue admitida en la Comunidad Económica Europea durante el régimen de Franco por razones políticas. Integrarse a la Comunidad Europea en enero de 1986 fue el último peldaño hacia la consolidación definitiva de la democracia en España y de la apertura de su economía.. Los resultados de los veinticinco años como miembro de la UE se han traducido en un impulso sin precedentes de modernización y progreso. España adoptó el “Acervo Comunitario” y recibió considerables beneficios de su integración a la Comunidad, eliminando barreras, siguiendo las políticas comunes, recibiendo fondos europeos y adoptando la moneda europea común. A partir de un nivel del 60% del promedio europeo de renta per capita en 1986, el nivel actual –incluso con la crisis que estalló en 2008- se sitúa en torno al 105 por ciento. Los últimos tres años han sido diferentes y difíciles como consecuencia de la severa crisis económica y financiera.En este contexto este trabajo analiza como los sucesivos gobiernos de España han organizado la gobernanza económica para adaptarla a los cambios cuantitativos y cualitativos que se han ido produciendo en la integración europea.

The Impact of EU Membership on the Economic Governance of Spain

[spa] España no fue admitida en la Comunidad Económica Europea durante el régimen de Franco por razones políticas. Integrarse a la Comunidad Europea en enero de 1986 fue el último peldaño hacia la consolidación definitiva de la democracia en España y de la apertura de su economía.. Los resultados de los veinticinco años como miembro de la UE se han traducido en un impulso sin precedentes de modernización y progreso. España adoptó el “Acervo Comunitario” y recibió considerables beneficios de su integración a la Comunidad, eliminando barreras, siguiendo las políticas comunes, recibiendo fondos europeos y adoptando la moneda europea común. A partir de un nivel del 60% del promedio europeo de renta per capita en 1986, el nivel actual –incluso con la crisis que estalló en 2008- se sitúa en torno al 105 por ciento. Los últimos tres años han sido diferentes y difíciles como consecuencia de la severa crisis económica y financiera.En este contexto este trabajo analiza como los sucesivos gobiernos de España han organizado la gobernanza económica para adaptarla a los cambios cuantitativos y cualitativos que se han ido produciendo en la integración europea.

Self-Organising Maps and Correlation Analysis as a Tool to Explore Patterns in Excitation-Emission Matrix Data Sets and to Discriminate Dissolved Organic Matter Fluorescence Components

Dissolved organic matter (DOM) is a complex mixture of organic compounds, ubiquitous in marine and freshwater systems. Fluorescence spectroscopy, by means of Excitation-Emission Matrices (EEM), has become an indispensable tool to study DOM sources, transport and fate in aquatic ecosystems. However the statistical treatment of large and heterogeneous EEM data sets still represents an important challenge for biogeochemists. Recently, Self-Organising Maps (SOM) has been proposed as a tool to explore patterns in large EEM data sets. SOM is a pattern recognition method which clusterizes and reduces the dimensionality of input EEMs without relying on any assumption about the data structure. In this paper, we show how SOM, coupled with a correlation analysis of the component planes, can be used both to explore patterns among samples, as well as to identify individual fluorescence components. We analysed a large and heterogeneous EEM data set, including samples from a river catchment collected under a range of hydrological conditions, along a 60-km downstream gradient, and under the influence of different degrees of anthropogenic impact. According to our results, chemical industry effluents appeared to have unique and distinctive spectral characteristics. On the other hand, river samples collected under flash flood conditions showed homogeneous EEM shapes. The correlation analysis of the component planes suggested the presence of four fluorescence components, consistent with DOM components previously described in the literature. A remarkable strength of this methodology was that outlier samples appeared naturally integrated in the analysis. We conclude that SOM coupled with a correlation analysis procedure is a promising tool for studying large and heterogeneous EEM data sets.

Heterosis in papaya: inter and intragroup analysis

Papaya (Carica papaya L.) is a typical crop of tropical areas, and Brazil is one of the leading world producers. In recent decades, papaya culture has expanded to different regions of the country, but the number of cultivars available is still limited. In the present study, a complete diallel cross was carried out using eight accessions of papaya from the UENF/Caliman germplasm bank. Four genotypes belong to the Formosa heterotic group and four, to the Solo group. This study aimed to evaluate the occurrence and viability of exploring heterosis in heterotic intragroup hybrids. Fifty-six hybrid progenies were generated and evaluated. Among the Formosa intragroup hybrids, two hybrid combinations (MR x J4 and MR x SK) showed heterosis for all traits, as well as good average total fruit production. Among the Solo intragroup hybrids, three hybrid combinations (WM x GG, WM x SS and WM x SM) stand out for fruit production and high content of soluble solids. In Formosa x Solo hybrids, all hybrid combinations with the parent JS (JS x WM, JS x GG, JS x SS and JS x SM) showed high fruit quality and good average for fruit production. The heterotic profile of the hybrids tested allowed the identification of promising hybrids within Formosa and Solo heterotic groups. The analysis of the canonical variables also allowed the visualization of distinct groups of hybrids, depending on the provenance of the parents.

Repeatability, correlation and path analysis of physical and chemical characteristics of peach fruits

This study aimed to determine the number of measurements necessary to evaluate physical and chemical characteristics of peach fruits, study the relationships between them and their direct and indirect effects on the content of ascorbic acid and total carotenoids. The characteristics skin and pulp color, fruit weight, suture, equatorial and polar diameters, firmness, soluble solids (SS), titratable acidity (TA), SS/TA ratio, ascorbic acid and total carotenoids were evaluated in 39 cultivars of peach and 3 cultivars of nectarine from the orchard of the Universidade Federal de Viçosa. The repeatability coefficient was estimated by ANOVA and CPCOR. Phenotypic correlation coefficients (rf) were estimated and, after the multicollinearity diagnostics, they were unfolded to direct and indirect effects of the explanatory variables on the response variable using path analysis. There was agreement on the magnitude of repeatability coefficients obtained by the two methods; however, they varied among the 14 characteristics. The highest correlations were found between FW, SD, ED and PD. Seven fruits are sufficient to evaluate the physical and chemical characteristics of peach with a correlation coefficient of 90%. The characteristics considered in the path diagrams (b* skin, hº skin, b* pulp, hº pulp, ED, PD, FIR, SS, SS/AT and TC) are not the main determinants of the ascorbic acid. The yellow hue of the pulp (hº pulp) has the potential to be used in indirect selection for total carotenoids.

A systematic review and meta-analysis of lithium augmentation of tricyclic and second generation antidepressants in major depression.

BACKGROUND: Lithium augmentation of antidepressants for treatment of unipolar major depression was one of the first adjunctive strategies based on a neuropharmacologic rationale. Randomized controlled trials supported its efficacy but most trials added lithium to tricyclic antidepressants (TCAs). Despite its efficacy, use of lithium augmentation remains infrequent. The current systematic review and meta-analysis examines the efficacy of lithium augmentation as an adjunct to second generation antidepressants as well as to TCAs and considers reasons for its infrequent use. METHOD: A systematic search of Medline and the Cochrane Clinical Trials database was performed. Randomized, placebo-controlled trials of lithium augmentation were selected. A fixed-effects meta-analysis was performed. Odds ratios for response were calculated for each treatment-control contrast, for the trials grouped by type of initial antidepressant (TCA or second generation antidepressant), and as a meta-analytic summary for all treatments combined. RESULTS: Nine trials that included 237 patients were selected. The odds ratio for response to lithium vs. placebo in all contrasts combined was 2.89 (95% CI 1.65, 5.05, z=3.72, p=0.0002). Heterogeneity was very low, I(2)=0%. Adjunctive lithium was effective with TCAs (7 contrasts) and with second generation agents (3 contrasts). Discontinuation due to adverse events was infrequent and did not differ between lithium and placebo. LIMITATIONS: The meta-analysis is limited by the small size and number of trials and limited data for treatment resistant patients. CONCLUSIONS: Adjunctive lithium appears to be as effective for second generation antidepressants as it was for the tricyclics.

Early transjugular intrahepatic portosystemic shunt in cirrhotic patients with acute variceal bleeding: a systematic review and meta-analysis of controlled trials.

INTRODUCTION: There is conflicting evidence on the benefit of early transjugular intrahepatic portosystemic shunt (TIPSS) on the survival of patients with acute variceal bleeding (AVB). AIM: To assess the effect of early TIPSS on patient prognosis. MATERIALS AND METHODS: We carried out a meta-analysis of trials evaluating early TIPSS in cirrhotic patients with AVB. RESULTS: Four studies were included. Early TIPSS was associated with fewer deaths [odds ratio (OR)=0.38, 95% confidence interval (CI)=0.17-0.83, P=0.02], with moderate heterogeneity between studies (P=0.15, I=44%). Early TIPSS was not significantly associated with fewer deaths among Child-Pugh B patients (OR=0.35, 95% CI=0.10-1.17, P=0.087) nor among Child-Pugh C patients (OR=0.34, 95% CI=0.10-1.11, P=0.074). There was no heterogeneity between studies in the Child-Pugh B analysis (P=0.6, I=0%), but there was a high heterogeneity in the Child-Pugh C analysis (P=0.06, I=60%). Early TIPSS was associated with lower rates of bleeding within 1 year (OR=0.08, 95% CI=0.04-0.17, P<0.001) both among Child-Pugh B patients, (OR=0.15, 95% CI=0.05-0.47, P=0.001) and among Child-Pugh C patients (OR=0.05, 95% CI=0.02-0.15, P<0.001), with no heterogeneity between studies. Early TIPSS was not associated with higher rates of encephalopathy (OR=0.84, 95% CI=0.50-1.42, P=0.5). CONCLUSION: Cirrhotic patients with AVB treated with early TIPSS had lower death rates and lower rates of clinically significant bleeding within 1 year compared with patients treated without early TIPSS. Additional studies are required to identify the potential risk factors leading to a poor prognosis after early TIPSS in patients with AVB and to determine the impact of the degree of liver failure on the patient's prognosis.

HETEROTIC GROUP FORMATION IN PSIDIUM GUAJAVA L. BY ARTIFICIAL NEURAL NETWORK AND DISCRIMINANT ANALYSIS

ABSTRACT The present study aimed at evaluating the heterotic group formation in guava based on quantitative descriptors and using artificial neural network (ANN). For such, we evaluated eight quantitative descriptors. Large genetic variability was found for the eight quantitative traits in the 138 genotypes of guava. The artificial neural network technique determined that the optimal number of groups was three. The grouping consistency was determined by linear discriminant analysis, which obtained classification percentage of the groups, with a value of 86 %. It was concluded that the artificial neural network method is effective to detect genetic divergence and heterotic group formation.

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

An outcome and cost analysis of anal fistula plug insertion vs endorectal advancement flap for complex anal fistulae.

AIM: The study aimed to compare the rate of success and cost of anal fistula plug (AFP) insertion and endorectal advancement flap (ERAF) for anal fistula. METHOD: Patients receiving an AFP or ERAF for a complex single fistula tract, defined as involving more than a third of the longitudinal length of of the anal sphincter, were registered in a prospective database. A regression analysis was performed of factors predicting recurrence and contributing to cost. RESULTS: Seventy-one patients (AFP 31, ERAF 40) were analysed. Twelve (39%) recurrences occurred in the AFP and 17 (43%) in the ERAF group (P = 1.00). The median length of stay was 1.23 and 2.0 days (P < 0.001), respectively, and the mean cost of treatment was euro5439 ± euro2629 and euro7957 ± euro5905 (P = 0.021), respectively. On multivariable analysis, postoperative complications, underlying inflammatory bowel disease and fistula recurring after previous treatment were independent predictors of de novo recurrence. It also showed that length of hospital stay ≤ 1 day to be the most significant independent contributor to lower cost (P = 0.023). CONCLUSION: Anal fistula plug and ERAF were equally effective in treating fistula-in-ano, but AFP has a mean cost saving of euro2518 per procedure compared with ERAF. The higher cost for ERAF is due to a longer median length of stay.

The Effect of Cigarette Smoking on Diabetic Peripheral Neuropathy: A Systematic Review and Meta-Analysis.

OBJECTIVE: Studies suggest that smoking may be a risk factor for the development of microvascular complications such as diabetic peripheral neuropathy (DPN). The objective of this study was to assess the relationship between smoking and DPN in persons with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS: A systematic review of the PubMed, Embase, and Cochrane clinical trials databases was conducted for the period from January 1966 to November 2014 for cohort, cross-sectional and case-control studies that assessed the relationship between smoking and DPN. Separate meta-analyses for prospective cohort studies and case-control or cross-sectional studies were performed using random effects models. RESULTS: Thirty-eight studies (10 prospective cohort and 28 cross-sectional) were included. The prospective cohort studies included 5558 participants without DPN at baseline. During follow-up ranging from 2 to 10 years, 1550 cases of DPN occurred. The pooled unadjusted odds ratio (OR) of developing DPN associated with smoking was 1.26 (95% CI 0.86-1.85; I(2) = 74%; evidence grade: low strength). Stratified analyses of the prospective studies revealed that studies of higher quality and with better levels of adjustment and longer follow-up showed a significant positive association between smoking and DPN, with less heterogeneity. The cross-sectional studies included 27,594 participants. The pooled OR of DPN associated with smoking was 1.42 (95% CI 1.21-1.65; I(2) = 65%; evidence grade: low strength). There was no evidence of publication bias. CONCLUSIONS: Smoking may be associated with an increased risk of DPN in persons with diabetes. Further studies are needed to test whether this association is causal and whether smoking cessation reduces the risk of DPN in adults with diabetes.

Distribution, Abundance and Molecular Analysis of Genus Barbadocladius Cranston & Krosch (Diptera, Chironomidae) in Tropical, High Altitude Andean Streams and Rivers

The distribution of the genus Barbadocladius Cranston & Krosch (Diptera: Chironomidae), previously reported from Chile to Bolivia, has extended northwards. Larvae, pupae and pupal exuviae of this genus have been found in the high mountain tropical streams of Peru to 9°22′56″, but are restricted to very high altitude streams (altitudes over 3,278 m asl) compared to the lower altitude streams (below 1,100 m asl) in which the genus is reported in Chile and Argentina. Based on morphological studies, both described species in the genus, Barbadocladius andinus Cranston & Krosch and Barbadocladius limay Cranston & Krosch, have been found in Peru as pupae or pupal exuviae. Morphological analysis of the larvae and pupae revealed no differences between the two described species from Patagonia and Peru, which are of similar size and with a similar armament of hooklets and spines in pupal tergites and sternites. However, molecular analysis of larvae and pupae revealed that in Peru, there are at least two different evolutionary lines, one distributed widely and another restricted to one site. Phylogenetic analysis (using cox1 mitochondrial sequences) of all available sequences of Barbadocladius shows that the Chilean and Argentinean material differs from that of Peru. Therefore, a total of four molecular segregates are identified, although morphologically, neither larvae nor the pupae may be differentiated.

Chest CT at a dose below 0.3 mSv : impact of iterative reconstruction on image quality and lung analysis

Le nombre d'examens tomodensitométriques (Computed Tomography, CT) effectués chaque année étant en constante augmentation, différentes techniques d'optimisation, dont les algorithmes de reconstruction itérative permettant de réduire le bruit tout en maintenant la résolution spatiale, ont étés développées afin de réduire les doses délivrées. Le but de cette étude était d'évaluer l'impact des algorithmes de reconstruction itérative sur la qualité image à des doses effectives inférieures à 0.3 mSv, comparables à celle d'une radiographie thoracique. Vingt CT thoraciques effectués à cette dose effective ont été reconstruits en variant trois paramètres: l'algorithme de reconstruction, rétroprojection filtrée versus reconstruction itérative iDose4; la matrice, 5122 versus 7682; et le filtre de résolution en densité (mou) versus spatiale (dur). Ainsi, 8 séries ont été reconstruites pour chacun des 20 CT thoraciques. La qualité d'image de ces 8 séries a d'abord été évaluée qualitativement par deux radiologues expérimentés en aveugle en se basant sur la netteté des parois bronchiques et de l'interface entre le parenchyme pulmonaire et les vaisseaux, puis quantitativement en utilisant une formule de merit, fréquemment utilisée dans le développement de nouveaux algorithmes et filtres de reconstruction. La performance diagnostique de la meilleure série acquise à une dose effective inférieure à 0.3 mSv a été comparée à celle d'un CT de référence effectué à doses standards en relevant les anomalies du parenchyme pulmonaire. Les résultats montrent que la meilleure qualité d'image, tant qualitativement que quantitativement a été obtenue en utilisant iDose4, la matrice 5122 et le filtre mou, avec une concordance parfaite entre les classements quantitatif et qualitatif des 8 séries. D'autre part, la détection des nodules pulmonaires de plus de 4mm étaient similaire sur la meilleure série acquise à une dose effective inférieure à 0.3 mSv et le CT de référence. En conclusion, les CT thoraciques effectués à une dose effective inférieure à 0.3 mSv reconstruits avec iDose4, la matrice 5122 et le filtre mou peuvent être utilisés avec confiance pour diagnostiquer les nodules pulmonaires de plus de 4mm.