Noether's Symmetry Theorem for Variational and Optimal Control Problems with Time Delay

We extend the DuBois-Reymond necessary optimality condition and Noether's symmetry theorem to the time delay variational setting. Both Lagrangian and Hamiltonian versions of Noether's theorem are proved, covering problems of the calculus of variations and optimal control with delays.Comment: This is a preprint of a paper whose final and definite form will appear in the international journal Numerical Algebra, Control and Optimization (NACO). Paper accepted for publication 15-March-201

Inhibition of the formation in vitro of putatively carcinogenic metabolites derived from S. Haematobium and O. Viverrini by Combination of Drugs with Antioxidants

Infections caused by Schistosoma haematobium and Opisthorchis viverrini are classified as carcinogenic. Although carcinogenesis might be a multifactorial process, it has been postulated that these helminth produce/excrete oxysterols and estrogen-like metabolites that might act as initiators of their infection-associated carcinogenesis. Current treatment and control of these infections rely on a single drug, praziquantel, that mainly targets the parasites and not the pathologies related to the infection including cancer. Thus, there is a need to search for novel therapeutic alternatives that might include combinations of drugs and drug repurposing. Based on these concepts, we propose a novel therapeutic strategy that combines drugs with molecule antioxidants. We evaluate the efficacy of a novel therapeutic strategy to prevent the formation of putative carcinogenic metabolites precursors and DNA adducts. Firstly, we used a methodology previously established to synthesize metabolites precursors and DNA adducts in the presence of CYP450. Then, we evaluated the inhibition of their formation induced by drugs and antioxidants alone or in combination. Drugs and resveratrol alone did not show a significant inhibitory effect while N-acetylcysteine inhibited the formation of most metabolite precursors and DNA adducts. Moreover, the combinations of classical drugs with antioxidants were more effective rather than compounds alone. This strategy might be a valuable tool to prevent the initiation of helminth infection-associated carcinogenesis.This work was financed by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia, in the framework of the projects "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274). N.V. also acknowledges support from FCT and FEDER (European Union), award number IF/00092/2014/CP1255/CT0004. FUNDING TEXT 2: Funding: This work was financed by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia, in the framework of the projects “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). N.V. also acknowledges support from FCT and FEDER (European Union), award number IF/00092/2014/CP1255/CT0004

Colite pseudomembranosa : uma casuística de internamentos

Introduction: pseudomembranous colitis (PMC) is an infectious disease that generally begins after antibiotic treatment. Objectives: Characterize the patients with PMC in two Services of a Central Hospital. Material and Methods: we considered the patients admitted in a Medicine (MS) and in a Gastroenterology (GES) Service with primary or secondary diagnosis of PMC, between January/1995 and July/2003 and registered the age, gender, clinical presentation, antibiotics (AB) and other risk factors, diagnostic procedures, complications and treatment. Results: we considered 80 patients (43 - GES and 37 - MS); Mean age - 68,6 ± 17,7 years; 52,5% were male; Antibiotic treatment in the previous 3 months - 85%; Mean time of antibiotic treatment - 10,5 ± 6,1 days. Most Commonly Involved Antibiotics: cephalosporins, amoxicillin/clavulanic acid and quinolones. Associated risk factors: renal insufficiency (22,5%); cardiac insufficiency (22,5%); previously dependent patient ( 36,3%). Diagnostic procedures: toxin search-58 patients ( in 36 ), colonoscopy - 62 ( in 53); culture - 23 (in 17 ). The mortality rate was 18,8% (n = 15); recurrence rate - 10% (n = 8). Therapeutics: metronidazol - 37 patients (46,3%); vancomycin - 24 (30%); metronidazol + vancomycin – 12 (15%). Differences Between Services: mean age (MS - 72,9 and GES - 64,9); admission criteria (GES - intestinal disorders, MS – respiratory infections); diagnostic procedures (colonoscopy more frequent in GES); therapeutic options (MS - metronidazol; GES - vancomycin and metronidazol + vancomycin). Conclusions: PMC is more common in older patients that were generally submitted to previous antibiotic treatment, especially with ß-lactamics. Considering two distinct Services we observed differences concerning age, co-morbility and risk factors that implied distinct diagnostic and therapeutic approaches

The antioxidants resveratrol and N-acetylcysteine enhance anthelmintic activity of praziquantel and artesunate against Schistosoma mansoni

Background: Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. Despite its celebrated performance for treatment and control of schistosomiasis and other platyhelminth infections, praziquantel has some shortcomings and the inability of this drug to counteract disease sequelae prompts the need for novel therapeutic strategies. Methods: Using a host-parasite model involving Biomphalaria glabrata and Schistosoma mansoni we established mechanical transformation of S. mansoni cercariae into newly transformed schistosomula (NTS) and characterized optimal culture conditions. Thereafter, we investigated the antischistosomal activity and ability of the antioxidants N-acetylcysteine (NAC) and resveratrol (RESV) to augment the performance of praziquantel and/or artesunate (AS) against larval stages of the parasite. Drug effects were evaluated by using an automated microscopical system to study live and fixed parasites and by transmission electron microscopy (TEM). Results: Transformation rates of cercariae to schistosomula reached ~ 70% when the manipulation process was optimized. Several culture media were tested, with M199 supplemented with HEPES found to be suitable for S. mansoni NTS. Among the antioxidants studied, RESV alone or combined with anthelminthic drugs achieved better results rather N-acetylcysteine (NAC). TEM observations demonstrated that the combination of AS + RESV induced severe, extensive alterations to the tegument and subtegument of NTS when compared to the constituent compounds alone. Two anthelmintic-antioxidant combinations, praziquantel-resveratrol [combination index (CI) = 0.74] and artesunate-resveratrol (CI = 0.34) displayed moderate and strong synergy, respectively. Conclusions: The use of viability markers including staining with propidium iodide increased the accuracy of drug screening assays against S. mansoni NTS. The synergies observed might be the consequence of increased action by RESV on targets of AS and PZQ and/or they may act through concomitantly on discrete targets to enhance overall antischistosomal action. Combinations of active agents, preferably with discrete modes of action including activity against developmental stages and/or the potential to ameliorate infection-associated pathology, might be pursued in order to identify novel therapeutic interventions.We express our deepest appreciation to Mrs. Maria Lurdes Delgado for expert maintenance of the schistosome life-cycle and her technical support NV acknowledges support from the Fundação para a Ciência e Tecnologia (FCT, Portugal) and FEDER (European Union) through Project Number IF/00092/2014/CP1255/CT0004. NV thanks FCT by IF position, Fundação Manuel António da Mota (FMAM, Portugal) and Pfizer Portugal for research group support. JMCC thanks FCT for UID/Multi/00211/2019 and Strategic Project UI211. PJB acknowledges support from award RO1CA164719 from the National Cancer Institute (NCI), National Institutes of Health (NIH), USA. The contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of the FCT, FMAM, the NCI, or the NIH

Numerical simulation of thin steel fiber self-compacting concrete structures

Steel Fiber Reinforced Self Compacting Concrete (SFRSCC) was developed and applied on the manufacture of structural façade panels composed of a grid ribbed system covered by a layer of 30 mm thickness. Panel prototypes of this structural system were tested using loading configurations that promote the flexural and the punching failure modes in order to assess the benefits of fiber reinforcement to the flexural and shear resistance of thin SFRSCC structural systems. A smeared multi-fixed crack model, implemented into a FEM-based computer program, was used to simulate the deformational behavior of the tested panel prototypes up to their failure. The fracture parameters characterizing the SFRSCC post-cracking behavior were obtained from inverse analysis, using the data derived from three point notched beam tests. The punching failure mode was well captured by adopting a softening diagram for both out-of-plane shear components.Fundação para a Ciência e a Tecnologia (FCT) - POCTI/ECM/57518/2004 “FICOFIRE - High performance fiber reinforced concrete of enhanced fire resistance”, bolsa de doutouramento SFRH/BD/23326/2005

Numerical Modeling of Eta Carinae Bipolar Outflows

In this paper, we present two-dimensional gas dynamic simulations of the formation and evolution of the eta-Car bipolar outflows. Adopting the interacting nonspherical winds model, we have carried out high-resolution numerical simulations, which include explicitly computed time-dependent radiative cooling, for different possible scenarios of the colliding winds. In our simulations, we consider different degrees of non-spherical symmetry for the pre-outburst wind and the great eruption of the 1840s presented by the eta-Car wind. From these models, we obtain important differences in the shape and kinematical properties of the Homunculus structure. In particular, we find an appropriate combination of the wind parameters (that control the degree of non-spherical symmetry) and obtain numerical experiments that best match both the observed morphology and the expansion velocity of the eta-Car bipolar shell. In addition, our numerical simulations show the formation of a bipolar nebula embedded within the Homunculus (the little Homunculus) developed from a secondary eruptive event suffered by the star in the 1890s, and also the development of tenuous, high velocity ejections in the equatorial region that result from the impact of the eruptive wind of the 1840s with the pre-outburst wind and that could explain some of the high speed features observed in the equatorial ejecta. The models were, however, unable to produce equatorial ejections associated to the second eruptive event.Comment: 33 pages, 9 figures, accepted by the Astrophysical Journa

Valores como predictores de satisfacción con la vida en los jóvenes

Numa perspectiva funcionalista, os valores são uma expressão cognitiva das necessidades humanas, princípios que orientam o comportamento para metas mais pessoais, sociais ou gerais de vida, cujo impacto psicossocial merece mais investigação. Neste estudo, analisou-se em que medida o tipo de orientação dos valores prediz a satisfação com a vida de 562 jovens portugueses (n = 303, 53,9% mulheres), com idades entre 14 e 22 anos (M = 16,9, DP = 1,71), que frequentam o ensino médio: via profissionalizante (63,7%) e regular (36,3%). Os jovens completaram o Questionário de Valores Básicos e a Escala de Satisfação com a Vida. Os resultados da análise de regressão linear indicam que a orientação dos valores explica menos de um quarto da variabilidade da satisfação com a vida, o que suscita a necessidade de se analisar o seu poder explicativo em conjunto com outras variáveis, por exemplo, de personalidade e sociocognitivas.In a functionalist perspective, values are a cognitive expression of human needs as well as principles that guide behaviors to personal, social or general life goals, whose psychosocial impact deserves more investigation. This study aimed to analyze whether the type of values orientation predicts life satisfaction in 562 Portuguese youths (n = 303, 53.9% women) aged 14 to 22 years (M = 16.9; SD = 1.71), attending high school studies, being 63.7% technical and (36.3%) regular high school.Students completed the Basic Values Survey and the Satisfaction With Life Scale. The results of the linear regression analyzes indicate that the values orientation explains less than a quarter of life satisfaction variability, which indicated the need to further analyze its explanatory power together with other variables, such as, personality and socio-cognitive.Desde el punto de vista funcional, los valores son una expresión cognitiva de las necesidades humanas, principios que orientan el comportamiento hacia metas más personales, sociales o generales de vida, cuyo impacto psicosocial necesita más investigación. En este estudio se analizó en qué medida el tipo de orientación de los valores predice la satisfacción con la vida de 562 jóvenes portugueses (n = 303, 53.9% mujeres), con edades entre 14 y 22 años ( = 16.9, P = 1.71) que frecuentan Enseñanza Secundaria: profesional (63.7%) y normal (36.3%). Los jóvenes completaron el Cuestionario de Valores Básicos y la Escala de Satisfacción con la Vida. Los resultados del análisis de regresión lineal indican que la orientación de los valores explica menos de una cuarta parte de la variabilidad de satisfacción con la vida, lo que plantea la necesidad de analizar su poder explicativo, junto con otras variables, por ejemplo, de personalidad y socio-cognitivas.(undefined)info:eu-repo/semantics/publishedVersio

Capsule endoscopy in inflammatory bowel disease type unclassified and indeterminate colitis serologically negative

BACKGROUND: The value of capsule endoscopy in the setting of inflammatory bowel disease type unclassified (IBDU) and indeterminate colitis (IC) remains obscure. The aim was to evaluate the clinical impact of capsule endoscopy on IBDU/IC patients with negative serology. METHODS: Eighteen patients with long-standing IBDU (n = 14) and IC (n = 4) were enrolled to undergo a capsule endoscopy and then followed prospectively. Lesions considered diagnostic of Crohn's disease (CD) were 4 or more erosions/ulcers and/or a stricture. The median follow-up time after capsule endoscopy was 32 ± 11 months (23-54 months). RESULTS: Total enteroscopy was possible in all patients. In 2 patients the examination was normal (Group 1). In 9 patients subtle findings were observed (Group 2): focal villi denudation (n = 1) and fewer than 4 erosions/ulcers (n = 8). In 7 patients, 4 or more erosions/ulcers were detected (Group 3), leading to a diagnosis of CD. However, their treatment was not reassessed on the basis of the capsule findings. Until now, a definitive diagnosis has been achieved in 2 additional patients: 1 from Group 1 (ulcerative colitis) and another patient from Group 2 (CD), who began infliximab infusions. Nine patients remained indeterminate at follow-up. CONCLUSIONS: Although capsule endoscopy enabled the diagnosis of CD in 7 patients, in none of them was the clinical management changed. Moreover, a change in therapy due to a diagnosis of CD was made for only 1 patient, who presented nonspecific findings. Our results suggest that capsule findings are not helpful in the work-up of these patient

Endoscopic treatment of bleeding gastric varices with histoacryl (N-butyl-2-cyanoacrylate): a South European single center experience

BACKGROUND: Endoscopic injection of N-butyl-2-cyanoacrylate is the current recommended treatment for gastric variceal bleeding. Despite the extensive worldwide use, there are still differences related to the technique, safety, and long term-results. We retrospectively evaluated the efficacy and safety of cyanoacrylate in patients with gastric variceal bleeding. PATIENTS AND METHODS: Between January 1998 and January 2010, 97 patients with gastric variceal bleeding underwent endoscopic treatment with a mixture of N-butyl-2-cyanoacrylate and Lipiodol(TM). Ninety-one patients had cirrhosis and 6 had non-cirrhotic portal hypertension. Child-Pugh score at presentation for cirrhotic patients was A-12.1 %; B-53.8 %; C-34.1 % and median MELD score at admission was 13 (3-26). Successful hemostasis, rebleeding rate and complications were reviewed. Median time of follow up was 19 months (0.5-126). RESULTS: A median mixture volume of 1.5 mL (0.6 to 5 mL), in 1 to 8 injections, was used, with immediate hemostasis rate of 95.9 % and early rebleeding rate of 14.4 %. One or more complications occurred in 17.5 % and were associated with the use of Sengstaken-Blakemore tube before cyanoacrylate and very early rebleeding (p < 0.05). Hospital mortality rate during initial bleeding episode was 9.3 %. Very early rebleeding was a strong and independent predictor for in-hospital mortality (p < 0.001). Long-term mortality rate was 58.8 %, in most of the cases secondary to hepatic failure. CONCLUSION: N-butyl-2-cyanoacrylate is a rapid, easy and highly effective modality for immediate hemostasis of gastric variceal bleeding with an acceptable rebleeding rate. Patients with very early rebleeding are at higher risk of death