Finite-size scaling considerations on the ground state microcanonical temperature in entropic sampling simulations

In this work we discuss the behavior of the microcanonical temperature $\frac{\partial S(E)}{\partial E}$ obtained by means of numerical entropic sampling studies. It is observed that in almost all cases the slope of the logarithm of the density of states $S(E)$ is not infinite in the ground state, since as expected it should be directly related to the inverse temperature $\frac{1}{T}$. Here we show that these finite slopes are in fact due to finite-size effects and we propose an analytic expression $a\ln(bL)$ for the behavior of $\frac{\varDelta S}{\varDelta E}$ when $L\rightarrow\infty$. To test this idea we use three distinct two-dimensional square lattice models presenting second-order phase transitions. We calculated by exact means the parameters $a$ and $b$ for the two-states Ising model and for the $q=3$ and $4$ states Potts model and compared with the results obtained by entropic sampling simulations. We found an excellent agreement between exact and numerical values. We argue that this new set of parameters $a$ and $b$ represents an interesting novel issue of investigation in entropic sampling studies for different models

Wang-Landau sampling in three-dimensional polymers

Monte Carlo simulations using Wang-Landau sampling are performed to study three-dimensional chains of homopolymers on a lattice. We confirm the accuracy of the method by calculating the thermodynamic properties of this system. Our results are in good agreement with those obtained using Metropolis importance sampling. This algorithm enables one to accurately simulate the usually hardly accessible low-temperature regions since it determines the density of states in a single simulation.Comment: 5 pages, 9 figures arch-ive/Brazilian Journal of Physic

Xanthinuria secondary to allopurinolt therapy in dogs with canine leishmaniosis : current perspectives of the Iberian Veterinary Community

Dissertação de Mestrado Integrado em Medicina VeterináriaA xantinúria é o maior efeito adverso urinário em cães com leishmaniose tratados com alopurinol. Apesar das medidas preventivas e de maneio serem essenciais aquando desta terapêutica, a informação atualizada acerca do maneio da xantinúria é escassa. Este estudo visou investigar a abordagem médica da comunidade médico veterinária ibérica (IVC) na prevenção e maneio da xantinúria secundária ao tratamento com alopurinol na leishmaniose canina (CanLeish). Foi realizado um estudo transversal que teve como base o desenvolvimento de um questionário online e anónimo o qual foi difundido nas redes sociais da IVC. Este questionário detalhou as características gerais dos inquiridos; os regimes de prescrição do alopurinol; a interrupção do alopurinol e os seus efeitos adversos; a deteção, complicações e diagnóstico da xantinúria, assim como as medidas preventivas e reativas da xantinúria. Foram obtidas 230 respostas (131 de Portugal e 99 de Espanha). A maioria dos inquiridos segue as recomendações internacionais quando usa o alopurinol no tratamento da CanLeish. Um total de 54.6% destes afirmou já ter interrompido a terapêutica antes da sua duração ideal devido ao aparecimento de efeitos adversos além da xantinúria. Cerca de 71.6% dos inquiridos já detetou xantinúria, sendo o aparecimento de sinais clínicos urinários, a complicação mais comum. O método de diagnóstico mais usado para xantinúria é a urianálise. Considerando a prevenção da xantinúria, 75.1% dos clínicos informam os donos sobre a possibilidade de surgirem efeitos adversos associados ao alopurinol, mas apenas 28.4% consideram fazer a transição para uma dieta com baixo teor em purinas. A realização de urianálise e controlos imagiológicos é considerada por 71.2% e 31% dos inquiridos, respetivamente, para monitorizar o tratamento com alopurinol. Após ser detetada xantinúria, a abordagem terapêutica dos inquiridos consiste na interrupção do alopurinol, na diminuição da sua dose, no aumento da frequência de administração ou na sua substituição. Cerca de 72.1% tomam outras medidas, destacando-se a transição para uma dieta com baixo teor de purinas. A frequência estimada de xantinúria na prática clínica diária foi considerada inferior a 25% por 91.7% dos veterinários. Estes resultados revelam que a IVC está consciente da xantinúria como uma complicação comum do tratamento com alopurinol na CanLeish. Apesar das medidas preventivas serem por vezes negligenciadas, os Médicos Veterinários Ibéricos aparentam conhecer as diversas opções que podem ser usadas no maneio da xantinúria.ABSTRACT - Xanthinuria secondary to allopurinolt therapy in dogs with canine leishmaniosis : current perspectives of the Iberian Veterinary Community - Xanthinuria is the major urinary adverse effect in dogs with leishmaniosis under allopurinol therapy. Although preventive and management measures are essential for its treatment, updated information about xanthinuria management in clinical practice is lacking. This study aimed to investigate the current medical approach of the Iberian Veterinary Community (IVC) on prevention and management of xanthinuria secondary to allopurinol therapy in canine leishmaniosis (CanLeish). A cross-sectional study was conducted based on an online anonymous survey which was diffused via Iberian social network veterinary groups. This questionnaire detailed: general characteristics of the respondents; allopurinol prescription regimens; allopurinol withdrawal and adverse effects; xanthinuria detection, complications, and diagnosis; xanthinuria preventive and reactive measures. A total of 230 answers were obtained from the IVC (131 from Portugal and 99 from Spain). Most clinicians follow international recommendations when using allopurinol in CanLeish therapies. A total of 54.6% of clinicians stated that they had stopped the therapy before its ideal duration due to the appearance of adverse effects other than xanthinuria. About 71.6% of clinicians have detected xanthinuria, being the appearance of urinary clinical signs, the most common complication detected. Urinalysis was the preferred diagnostic method to detect xanthinuria. Considering its prevention, 75.1% of clinicians inform owners about possible adverse effects of allopurinol therapies, although only 28.4% consider an appropriate dietary change to a low purine diet. Urinalysis and imaging controls are used by 71.2% and 31% of clinicians, respectively, to monitor allopurinol therapies. When facing xanthinuria, measures concerning allopurinol therapy are considered, such as discontinuing it, reducing its dosage, increasing its administration frequency, or replacing it. Also, 72.1% of clinicians take other measures, with emphasis on the transition to a low-purine diet. Finally, the estimated frequency of xanthinuria in their daily practice was considered less than 25%, by 91.7% of veterinary surgeons. These findings show that the IVC is aware that xanthinuria is a common complication in CanLeish allopurinol therapies. Although preventive measures are often neglected, clinicians seem to be conscious about the different options that can be used to manage xanthinuria.N/

Synthesis and characterization of ionic Liquids and evaluation of their applicability in new pharmaceutical formulations

Los líquidos iónicos (LIs) han ido despertando interés hacia el estudio de su aplicabilidad en diferentes campos, especialmente debido a su gran versatilidad. La posibilidad de diseñar correctamente LIs para mostrar diferentes funcionalidades puede ser una estrategia prometedora para optimizar su aplicabilidad y resolver una variedad de desafíos en el área farmacéutica. La baja solubilidad en agua se ha señalado como una de las dificultades más comunes y, por lo tanto, una de las principales preocupaciones de la industria farmacéutica, ya que la baja solubilidad puede comprometer la biodisponibilidad, la eficacia terapéutica y la incorporación de fármacos en los sistemas de administración. A la luz de esto, esta tesis aborda cómo diferentes combinaciones de LIs catión-anión pueden influir en la capacidad de los LIs para mejorar la solubilidad y la carga de compuestos poco solubles en agua con interés farmacológico, considerando su seguridad y evaluando si el uso de LIs permite la mantenimiento de los efectos biológicos de esos compuestos. En este contexto, en primer lugar, se sintetizaron ocho LIs combinando diferentes cationes (colinio o imidazolio) y aniones (bromuro o aminoácidos). Teniendo en cuenta su aplicabilidad potencial como potenciadores de la solubilidad para la administración tópica, la citotoxicidad de los LIs sintetizadas en las células HaCaT y el impacto de sus diferentes combinaciones de cationes y aniones en la solubilidad de cuatro compuestos fenólicos poco solubles en agua (ácidos ferúlico, cafeico y p-cumárico y rutina) fueron evaluados. El grupo de cabeza catiónica, la longitud de la cadena lateral catiónica y el anión influyeron en la toxicidad de los LIs. Por otro lado, en términos de solubilidad del fármaco, parecían ser los aniones los que tenían el mayor impacto en esta propiedad, con todos los LIs basados en aminoácidos aumentando la solubilidad de los compuestos estudiados. Posteriormente se estudió la capacidad de los LIs basados en aminoácidos de colina para permitir una mayor carga de fármaco en formulaciones tópicas y su influencia en la toxicidad potencial para las células MDA-MB-231 y la actividad de eliminación de radicales del ácido ferúlico y la rutina. La exposición al ácido ferúlico y la rutina no causó efectos citotóxicos en las células de cáncer de mama. Los LIs basados en aminoácidos de colina, en concentraciones no tóxicas, mejoraron considerablemente la carga del fármaco en las emulsiones O/W desarrolladas combinadas con LIs, sin influir en la actividad de eliminación de radicales de los compuestos estudiados, la viabilidad celular o la estabilidad de las formulaciones desarrolladas. Luego, dado que no se observaron efectos citotóxicos en células MDA-MB-231, se estudió la citotoxicidad de los ácidos ferúlico, cafeico y p-cumárico en células 786-O. El tratamiento con ácidos cafeico y p-cumárico indujo, a mayores concentraciones, una disminución significativa de la viabilidad celular. También se evaluaron los posibles efectos citotóxicos de la rutina en las células 786-O, considerando su seguridad en las células Vero normales. La rutina provocó una disminución dependiente de la concentración de la viabilidad celular en ambas líneas celulares, sin embargo, se observó un efecto más significativo en las células de cáncer renal. Estos resultados prometedores llevaron a explorar más a fondo el impacto de la rutina, individualmente y en combinación, con LIs a base de aminoácidos de colina en la viabilidad celular y la progresión del ciclo celular de las células renales, así como la aplicabilidad de estos LIs para mejorar el suministro de rutina. La exposición a la rutina provocó un aumento significativo en la población sub-G1 de células 786-O. Los dos LIs basados en aminoácidos de colina no afectaron los efectos de la rutina y, en concentraciones no tóxicas, permitieron mejorar la solubilidad del fármaco de la rutina y la carga en los nanosistemas de LI, sin afectar la estabilidad y el rendimiento de los sistemas de administración preparados. Este estudio enfatizó la importancia de diseñar correctamente los LIs para una aplicación en particular. El ajuste de las propiedades de los LIs, a través de diferentes combinaciones de aniones y cationes, puede influir en su citotoxicidad y capacidad para mejorar la solubilidad del fármaco. Estos son dos factores extremadamente importantes cuando se pretende utilizar LIs como potenciadores de la solubilidad en concentraciones no tóxicas. Además, este trabajo reveló que la rutina podría usarse potencialmente en el cáncer renal humano. Además, la combinación de rutina con los LIs demostró ser crucial al permitir mejorar la solubilidad e incorporación de este compuesto en los sistemas de administración sin tener un impacto en su efectividad. En general, los LIs demostraron ser una herramienta versátil y valiosa para el área farmacéutica, ya que pueden mejorar la aplicabilidad de compuestos poco solubles en agua con interés farmacológico. Palabras clave: Síntesis, líquidos iónicos, compuestos fenólicos, aplicabilidad segura, solubilidad, citotoxicidad, formulaciones farmacéuticas

Short-time behavior of a classical ferromagnet with double-exchange interaction

We investigate the critical dynamics of a classical ferromagnet on the simple cubic lattice with double-exchange interaction. Estimates for the dynamic critical exponents $z$ and $\theta$ are obtained using short-time Monte Carlo simulations. We also estimate the static critical exponents $\nu$ and $\beta$ studying the behavior of the samples at an early time. Our results are in good agreement with available estimates and support the assertion that this model and the classical Heisenberg model belong to the same universality class

How I treat metastatic triple-negative breast cancer

Triple-negative breast cancer (TNBC) is associated with a high risk of recurrence and generally a bad prognosis. More than one-third of patients with TNBC will present distant metastases during the course of their disease. Although chemotherapy has been the main treatment option for metastatic TNBC for a long time, this scenario has changed recently with the advent of the polyadenosine diphosphate-ribose polymerase inhibitors (PARPis) for patients harbouring a mutation in the BRCA genes (BRCAmut) and also with the results of immunotherapy in patients with PD-L1-positive tumours. The present manuscript proposes a treatment algorithm for patients with metastatic TNBC based on the currently available, most relevant literature on the topic. For patients with a BRCAmut and able to tolerate chemotherapy, we recommend initiating treatment with platins (carboplatin/cisplatin) and to start PARPis at disease progression. For patients with PD-L1-positive tumours (PD-L1 expression on tumour-infiltrating immune cells >= 1%), we recommend first-line treatment with nab-paclitaxel and atezolizumab, when available. In patients without a BRCA mutation and with PD-L1-negative tumours, we recommend single-agent chemotherapy with taxanes (paclitaxel or docetaxel) as a first-line treatment. In patients with a high disease burden or who are very symptomatic, combinations such as anthracyclines plus cyclophosphamide or platins with taxanes are valid options. Chemotherapy should be maintained until the occurrence of disease progression or limiting toxicities. After progression to first-line chemotherapy, anthracyclines are an option for patients who received taxanes and vice versa. For patients who progressed to taxanes and anthracyclines, or who present contraindications to these agents, fluorouracil/capecitabine, eribulin, gemcitabine, cisplatin/carboplatin, vinorelbine and ixabepilone are alternatives. The treatment of TNBC is constantly evolving, and the inclusion of patients in ongoing trials evaluating new targeted agents, immunotherapy and predictive biomarkers should be encouraged, in an attempt to improve metastatic TNBC treatment outcomes

Recursos educacionais abertos para a dinamização da leitura no 1º ciclo do ensino básico

Num contexto de um mundo cada vez mais digital, pautado por um desenvolvimento tecnológico extremamente acelerado, assistimos a profundas mudanças nos mais variados setores da sociedade. A informação veicula a uma velocidade estonteante pela internet, favorecendo a partilha e a colaboração na criação de conhecimento. Conceitos como Educação Aberta e em Rede surgem por todo o mundo, efetivando-se com a criação e disponibilização de Recursos Educacionais Abertos, demonstrando em conjunto com as Tecnologias Digitais disponíveis uma nova forma de estar na Educação e a abertura para a inclusão de novos modelos e práticas pedagógicas. O projeto apresentado neste documento constitui a criação e desenvolvimento de um Recurso Educacional Aberto (REA) dirigido a professores do 1º Ciclo do Ensino Básico, apresentando um programa de dinamização da leitura recreativa assente nas Tecnologias Digitais e nas ferramentas da web, para ser aplicado dentro e fora da sala de aula. Desenvolvido através duma abordagem metodológica da design-based research, o referido Projeto encontra-se integrado no projeto de investigação Web Social e Educação Online no Laboratório de Educação a Distância e Elearning (LE@D). Numa primeira parte deste documento, efetua-se a revisão bibliográfica dedicada a conceitos como Educação Aberta e Recursos Educacionais Abertos. Analisa-se ainda Tecnologias Digitais Abertas assim como a sua aplicação em sala de aula, referindo-se também o modelo TPACK que inspirou a criação do REA. Sustentando-se metodologicamente na design-based research (DBR), todo o processo de criação do REA desenvolveu-se em ciclos interativos na tentativa de aperfeiçoamento do mesmo. Ao longo do processo, desenhou-se o programa e todos os materiais, guiões e tutoriais explicativos, efetuando-se a sua validação junto de duas escolas do 1º Ciclo do Ensino Básico, numa perspetiva de análise da implementação e correção do programa. Da análise e avaliação de todo o processo resultaram recomendações e definiram-se caminhos a seguir, que são apresentados neste documento.In the context of an increasingly digital world, marked by an extremely accelerated technological development, we are seeing great changes on the most different areas of society. Information runs on an overwhelming speed over the internet, favoring the sharing and collaboration on knowledge creation. Concepts such as Open Education or Networked emerge all over the world, taking effect with the creation and availability of Open Educational Resources, demonstrating together within the available Digital Technologies a new way of approaching Education and the willing to include new models and pedagogic practices. The project presented in this document constitutes the creation and development of an Open Educational Resource (OER) aimed at teachers of the first cycle of basic education, presenting a project to boost recreational reading built on digital technologies and on web tools to be used inside and outside of the classroom. Developed through the Design Based Research methodological approach, the aforementioned project finds itself integrated into the investigation project called “Web Social e Educação Online” at Laboratório de Educação a Distância e Elearning (LE@D). The first part of this document contains a bibliographical review dedicated to concepts such as Open Education and Open Educational Resources. Open Digital Technologies are also analyzed, as well as their application on the classroom, referring the TPACK model too, which inspired the creation of OER. Based methodologically on the Design Based Research (DBR), all the creation process of REA developed in interactive cycles trying to improve itself. Throughout the process, the program and all the scriptwriting materials and explaining tutorials were designed and its validation was carried out at two schools of the first cycle of basic education from the perspective of analyzing the implementation and correction of the program. From the analysis and validation of all the process, resulted recommendations and were defined the paths to follow, which are presented in this document

FOLFIRI as second-line treatment of metastatic biliary tract cancer patients

The combination of cisplatin and gemcitabine is the standard first-line treatment of metastatic biliary tract cancer (BTC) patients. The benefit of second-line chemotherapy in these patients is controversial. This study aims to evaluate the activity of FOLFIRI (fluorouracil and irinotecan) after failure to the first-line platinum and gemcitabine-based chemotherapy in metastatic BTC patients. We present a single-institution, retrospective cohort study. Patients with locally advanced or metastatic BTC who progressed after at least one line of chemotherapy, consecutively treated at our Institution between 2007 and 2017 were included. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), clinical benefit rate (CBR) and safety profile of FOLFIRI. Twelve patients were included in the analysis, with a median follow up of 5 months (95% CI 2.77-7.20). The median number of cycles received was 3 (range 1 to 9). Four grade 3 toxicities were recorded; no grade 4 toxicities and no treatment-related deaths occurred. The median PFS was 1.7 months (95% CI; 0.66-2.67), and median OS was 5 months (95% CI; 2.77-7.20). Two patients presented stable disease, providing a CBR of 17%. We concluded that FOLFIRI presented a favorable toxicity profile and a modest activity in metastatic BTC patients who had progressed to platinum and gemcitabine and may be considered in patients who are able to tolerate additional lines of chemotherapy. Immunotherapy and targeted therapies selected according to the tumoral genomic profile are promising alternatives to improve the outcomes of second-line treatment in BTC