Multiscale Bone Remodelling with Spatial P Systems

Many biological phenomena are inherently multiscale, i.e. they are characterized by interactions involving different spatial and temporal scales simultaneously. Though several approaches have been proposed to provide "multilayer" models, only Complex Automata, derived from Cellular Automata, naturally embed spatial information and realize multiscaling with well-established inter-scale integration schemas. Spatial P systems, a variant of P systems in which a more geometric concept of space has been added, have several characteristics in common with Cellular Automata. We propose such a formalism as a basis to rephrase the Complex Automata multiscaling approach and, in this perspective, provide a 2-scale Spatial P system describing bone remodelling. The proposed model not only results to be highly faithful and expressive in a multiscale scenario, but also highlights the need of a deep and formal expressiveness study involving Complex Automata, Spatial P systems and other promising multiscale approaches, such as our shape-based one already resulted to be highly faithful.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005

Modelling of Multi-Agent Systems: Experiences with Membrane Computing and Future Challenges

Formal modelling of Multi-Agent Systems (MAS) is a challenging task due to high complexity, interaction, parallelism and continuous change of roles and organisation between agents. In this paper we record our research experience on formal modelling of MAS. We review our research throughout the last decade, by describing the problems we have encountered and the decisions we have made towards resolving them and providing solutions. Much of this work involved membrane computing and classes of P Systems, such as Tissue and Population P Systems, targeted to the modelling of MAS whose dynamic structure is a prominent characteristic. More particularly, social insects (such as colonies of ants, bees, etc.), biology inspired swarms and systems with emergent behaviour are indicative examples for which we developed formal MAS models. Here, we aim to review our work and disseminate our findings to fellow researchers who might face similar challenges and, furthermore, to discuss important issues for advancing research on the application of membrane computing in MAS modelling.Comment: In Proceedings AMCA-POP 2010, arXiv:1008.314

Influência de diferentes agentes auxiliares do preparo biomecânico na obturação de canais laterais artificiais

The purpose of the present study was to evaluate the influence of some auxiliary agents of biomechanical preparation of the root canal on the filling of artificial lateral canals in extracted human teeth. A total of eighty single-rooted teeth were employed, which were submitted to preparation of three artificial lateral canals in one of the proximal aspects at the cervical, middle and apical thirds, besides one in the buccal aspect. The main canals were prepared by Profile 0.4 rotary instruments through the crown-down technique and irrigated with the irrigants investigated, as follows: Group A - 1% sodium hypochlorite and final irrigation with trisodium EDTA for 5 minutes; Group B - Endogel (2% chlorhexidine gel); Group C - Endo PTC and Dakin's solution and final irrigation with Tergentol- Furacin; and Group D - File Eze. The root canals were obturated by the Tagger's hybrid technique and then radiographed for assessment of the penetration rate of the filling materials in the lateral canals. Analysis of the results demonstrated no statistically significant difference (pObjetivou-se avaliar a influência de alguns agentes auxiliares do preparo biomecânico do canal radicular, na obturação de canais laterais artificiais em dentes humanos extraídos. Foram utilizados oitenta dentes unirradiculados nos quais, previamente, foram confeccionados três canais laterais artificiais em uma das paredes proximais, nos terços cervical, médio e apical e um canal na parede vestibular. Os canais principais foram preparados com instrumentação rotatória, instrumentos Profile 0.4, pela técnica rotatória coroa- ápice e irrigados com a substância irrigadora estudada, sendo no grupo A - hipoclorito de sódio a 1% e irrigação final com EDTA trissódico por 5 minutos; grupo B - Endogel (gel de clorexidina a 2%); grupo C - Endo PTC e solução de Dakin e irrigação final com tergentol-furacin segundo a técnica de Paiva e Antoniazzi e no grupo D - File Eze. Os canais foram obturados pela técnica híbrida de Tagger e, então, radiografados para a análise das extensões de penetração dos materiais obturadores nos canais laterais. Após a análise dos resultados, conclui-se que não houve diferença estatística significante (

Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Validation of the TROPOspheric Monitoring Instrument (TROPOMI) surface UV radiation product

The TROPOspheric Monitoring Instrument (TROPOMI) onboard the Sentinel-5 Precursor (S5P) satellite was launched on 13 October 2017 to provide the atmospheric composition for atmosphere and climate research. The S5P is a Sun-synchronous polar-orbiting satellite providing global daily coverage. The TROPOMI swath is 2600 km wide, and the ground resolution for most data products is 7:23:5 km2 (5:63:5 km2 since 6 August 2019) at nadir. The Finnish Meteorological Institute (FMI) is responsible for the development of the TROPOMI UV algorithm and the processing of the TROPOMI surface ultraviolet (UV) radiation product which includes 36 UV parameters in total. Ground-based data from 25 sites located in arctic, subarctic, temperate, equatorial and Antarctic areas were used for validation of the TROPOMI overpass irradiance at 305, 310, 324 and 380 nm, overpass erythemally weighted dose rate/UV index, and erythemally weighted daily dose for the period from 1 January 2018 to 31 August 2019. The validation results showed that for most sites 60 % 80% of TROPOMI data was within 20% of ground-based data for snow-free surface conditions. The median relative differences to ground-based measurements of TROPOMI snow-free surface daily doses were within 10% and 5% at two-Thirds and at half of the sites, respectively. At several sites more than 90% of cloud-free TROPOMI data was within 20% of groundbased measurements. Generally median relative differences between TROPOMI data and ground-based measurements were a little biased towards negative values (i.e. satellite data ground-based measurement), but at high latitudes where non-homogeneous topography and albedo or snow conditions occurred, the negative bias was exceptionally high: from 30% to 65 %. Positive biases of 10 % 15% were also found for mountainous sites due to challenging topography. The TROPOMI surface UV radiation product includes quality flags to detect increased uncertainties in the data due to heterogeneous surface albedo and rough terrain, which can be used to filter the data retrieved under challenging conditions

Femara® and the future: tailoring treatment and combination therapies with Femara

Long-term estrogen deprivation treatment for breast cancer can, in some patients, lead to the activation of alternate cellular pathways, resulting in the re-emergence of the disease. This is a distressing scenario for oncologists and patients, but recent intensive molecular and biochemical studies are beginning to unravel these pathways, revealing opportunities for new targeted treatments. Far from making present therapies redundant, these new discoveries open the door to novel combination therapies that promise to provide enhanced efficacy or overcome treatment resistance. Letrozole, one of the most potent aromatase inhibitors, is the ideal candidate for combination therapy; indeed, it is one of the most intensively studied aromatase inhibitors in the evolving combinatorial setting. Complementary to the use of combination therapy is the development of molecular tools to identify patients who will benefit the most from these new treatments. Microarray gene profiling studies, designed to detect letrozole-responsive targets, are currently under way to understand how the use of the drug can be tailored more efficiently to specific patient needs

Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications

BACKGROUND Limited information exists about the epidemiology and outcome of surgical patients at increased risk of postoperative pulmonary complications (PPCs), and how intraoperative ventilation was managed in these patients. OBJECTIVES To determine the incidence of surgical patients at increased risk of PPCs, and to compare the intraoperative ventilation management and postoperative outcomes with patients at low risk of PPCs. DESIGN This was a prospective international 1-week observational study using the ‘Assess Respiratory Risk in Surgical Patients in Catalonia risk score’ (ARISCAT score) for PPC for risk stratification. PATIENTS AND SETTING Adult patients requiring intraoperative ventilation during general anaesthesia for surgery in 146 hospitals across 29 countries. MAIN OUTCOME MEASURES The primary outcome was the incidence of patients at increased risk of PPCs based on the ARISCAT score. Secondary outcomes included intraoperative ventilatory management and clinical outcomes. RESULTS A total of 9864 patients fulfilled the inclusion criteria. The incidence of patients at increased risk was 28.4%. The most frequently chosen tidal volume (VT) size was 500 ml, or 7 to 9 ml kg1 predicted body weight, slightly lower in patients at increased risk of PPCs. Levels of positive end-expiratory pressure (PEEP) were slightly higher in patients at increased risk of PPCs, with 14.3% receiving more than 5 cmH2O PEEP compared with 7.6% in patients at low risk of PPCs (P < 0.001). Patients with a predicted preoperative increased risk of PPCs developed PPCs more frequently: 19 versus 7%, relative risk (RR) 3.16 (95% confidence interval 2.76 to 3.61), P < 0.001) and had longer hospital stays. The only ventilatory factor associated with the occurrence of PPCs was the peak pressure. CONCLUSION The incidence of patients with a predicted increased risk of PPCs is high. A large proportion of patients receive high VT and low PEEP levels. PPCs occur frequently in patients at increased risk, with worse clinical outcome

Família: representações sociais de trabalhadores da Estratégia Saúde da Família

A família vem ocupando um lugar central nas políticas públicas, principalmente no setor saúde, através da Estratégia Saúde da Família. Essa centralidade foi fruto de um processo histórico e cultural de significações, por vezes normativas, sobre a família. Nesse processo, situam-se os trabalhadores da Estratégia Saúde da Família (ESF) enquanto atores sociais que constroem suas práticas e concepções sobre famílias dentro de uma realidade social permeada por contradições. Considerando as Representações Sociais como instrumento para identificação de uma realidade social, esse estudo se vale dessa abordagem para descrever as representações sociais de família construídas por trabalhadores da ESF. A pesquisa foi realizada em uma Unidade Básica de Saúde da Família da periferia de São Paulo, com um representante de cada categoria profissional que compõe as equipes de saúde da família. O material analisado demonstrou limitações no processo de formação dos trabalhadores no que se refere aos temas família e comunidade. As representações apontam para uma visão ampliada das configurações familiares, porém percebe-se uma desvalorização das camadas populares. São permeadas por sentimentos de angústia, principalmente quando se referem às famílias atendidas na ESF. Porém, podem-se vislumbrar possibilidades de construção de projetos de saúde eficazes, caso haja investimento na formação desses trabalhadores, visto que eles não se mostram indiferentes às necessidades de saúde das famílias atendidas na ESF.In Brazil, the family has been occupying a central place in public policies, mainly in the health sector, through Estratégia Saúde da Família (ESF - Family Health Strategy). This centralization is the result of a historical and cultural process of significations which, at times, created regulations over the family. In this process, the ESF workers exist as social actors who construct their practices and concepts about families within a social reality permeated with contradictions. Considering Social Representations as an instrument to identify a social reality, this study uses this approach to describe the social representations of family constructed by ESF workers. The study was carried out in a primary health care unit located in the periphery of São Paulo, with a representative from each of the professional categories that compose the family health care teams. The analyzed material demonstrated limitations in the training process of the workers regarding the family and community theme. The representations show a wider view of family configurations, but an underestimation of the less privileged class is noted. These representations are permeated with feelings of anxiety, principally when the families referred to are the ones followed up by the ESF. However, possibilities to construct efficient health care projects can exist if there is investment in the training of these professionals, since health care workers are not indifferent to the health needs of the families that are assisted by the ESF

Clinical trials update: endocrine and biological therapy combinations in the treatment of breast cancer

A greater understanding of the biological mechanisms responsible for de novo and acquired endocrine resistance has led to the rational design of clinical trials exploring the benefit of combining hormonal therapies with novel biological agents in an effort to enhance the efficacy of ER+ breast cancer treatment. These studies are increasingly including parallel biological analyses to elucidate the molecular characteristics of those tumors that are most likely to respond to specific targeted/endocrine combinations in an effort to develop a tailored approach to the management of individual patients. Unfortunately despite encouraging preclinical data, some of these combinations have yielded disappointing results in the clinical setting. This article will review the results of clinical trials of endocrine/biological combinations conducted in early and advanced breast cancer as well as provide an update on ongoing studies