A novel automata-theoretic approach to timeline-based planning

Timeline-based planning is a well-established approach successfully employed in a number of application domains. A very restricted fragment, featuring only bounded temporal relations and token durations, is expressive enough to capture action-based temporal planning. As for computational complexity, it has been shown to be EXPSPACE-complete when unbounded temporal relations, but only bounded token durations, are allowed. In this paper, we present a novel automata-theoretic characterisation of timeline-based planning where the existence of a plan is shown to be equivalent to the nonemptiness of the language recognised by a nondeterministic finite-state automaton that suitably encodes all the problem constraints (timelines and synchronisation rules). Besides allowing us to restate known complexity results in a fairly natural and compact way, such an alternative characterisation makes it possible to finally establish the exact complexity of the full version of the problem with unbounded temporal relations and token durations, which was still open and turns out to be EXPSPACE-complete. Moreover, the proposed technique is general enough to cope with (infinite) recurrent goals, which received little attention so far, despite being quite common in real-word application scenarios

Chromosome 1p13 genetic variants antagonize the risk of myocardial infarction associated with high ApoB serum levels

PMCID: PMC3480949This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Robotic Monitoring of Habitats: the Natural Intelligence Approach

In this paper, we first discuss the challenges related to habitat monitoring and review possible robotic solutions. Then, we propose a framework to perform terrestrial habitat monitoring exploiting the mobility of legged robotic systems. The idea is to provide the robot with the Natural Intelligence introduced as the combination of the environment in which it moves, the intelligence embedded in the design of its body, and the algorithms composing its mind. This approach aims to solve the challenges of deploying robots in real natural environments, such as irregular and rough terrains, long-lasting operations, and unexpected collisions, with the final objective of assisting humans in assessing the habitat conservation status. Finally, we present examples of robotic monitoring of habitats in four different environments: forests, grasslands, dunes, and screes

Life course association of maternal smoking during pregnancy and offspring's height: data from the 1993 Pelotas (Brazil) birth cohort

Health from birth to adolescence: findings from the 1993 Pelotas, Brazil, Birth Cohort StudyPURPOSE: To evaluate the effect of (1) maternal smoking during pregnancy; and (2) partner smoking on offspring's height in infancy, childhood, and adolescence. METHODS: All hospital live births from 1993 (5,249) were identified, and these infants were followed up at several ages. Height for age, expressed as z-scores using the World Health Organization growth curves, was measured at all follow-up visits. Maternal smoking during pregnancy was collected retrospectively at birth and analyzed as number of cigarettes/day smoked categorized in four categories (never smoked, <10, 10-19, and ≥ 20 cigarettes/day). Partner smoking was analyzed as a dichotomous variable (No/Yes). Unadjusted and adjusted analyses were performed by use of linear regression. RESULTS: The prevalence of self-reported maternal smoking during pregnancy was 33.5%. In the crude analysis, the number of cigarettes/day smoked by the mother during pregnancy negatively affected offspring's height in infancy, childhood, and adolescence. After adjustment for confounders and mediators, this association remained statistically significant, although the magnitude of the regression coefficients was reduced. Paternal smoking was not associated with offspring's height in the adjusted analyses. CONCLUSIONS: In addition to the well-known harmful effects of smoking, maternal smoking during pregnancy negatively affects offspring's height. Public health policies aimed at continuing to reduce the prevalence of maternal smoking during pregnancy must be encouraged.Jeovany Martínez-Mesa, Ana M.B. Menezes, David A. González, Bernardo L. Horta, Alicia Matijasevich, Denise P. Gigante, Pedro C. Halla

Maternal depression and anxiety predicts the pattern of offspring symptoms during their transition to adulthood

Background. Episodes of depression and anxiety (D&A) during the transition from late adolescence to adulthood, particularly when persistent, are predictive of long-term disorders and associated public health burden. Understanding risk factors at this time is important to guide intervention. The current objective was to investigate the associations between maternal symptoms of D&A with offspring symptoms during their transition to adulthood. Method. Data from a large population-based birth cohort study, in South Brazil, were used. Prospective associations between maternal D&A and offspring risk of these symptoms during the transition to adulthood (18/19, 24 and 30 years) were estimated. Results. Maternal D&A in adolescence was associated with offspring symptoms across the transition to adulthood, associations were consistently stronger for females than for males. Daughters whose mothers reported D&A were 4.6 times (95% confidence interval 2.71–7.84) as likely to report D&A at all three time-points, than daughters of symptom-free mothers. Conclusions. Maternal D&A is associated with persistent D&A during the daughter’s transition to adulthood. Intervention strategies should consider the mother’s mental health

Selecting b-thalassemia patients for gene therapy: a decision-making algorithm

The Societ\ue0 Italiana Talassemie ed Emoglobinopatie (Italian Society of Thalassemias and Hemoglobinopathies, SITE) has developed this document based on multidisciplinary discussions of a panel of experts to provide guidance on the identification and selection of patients with transfusion-dependent beta-thalassemia (\u3b2-TDT) who could benefit from gene therapy. Currently, allogeneic transplantation of hematopoietic stem cells is the only curative and most widely used therapy treatment for \u3b2-TDT. However, recent trials of gene therapy have reported very promising results in terms of overall survival and thalassemia-free survival and are opening a new landscape of treatment. This algorithm for the selection of patients suitable for gene therapy and the supporting notes were formulated by consensus review after an evaluation of currently available scientific evidence using validated criteria. The evidence was interpreted with caution because clinical trial experience of gene therapy is currently limited, a conventional treatment is available for patients with \u3b2-TDT and the availability of gene therapy will, at least initially, be quite limited. Clinical experience of allogeneic transplantation in \u3b2-TDT, which began in 1981, immediately showed the importance of patient risk stratification in order to achieve the best results (see the Pesaro experience and their classification of patients according to risk). Published data in the literature and the recent analysis of clinical evidence by the European Registry of Hemoglobinopathies of a large number of patients (2011 and 2018 analyses) confirm that young patient age (&lt;14 years) and the availability of a human leukocyte antigen (HLA)-identical family donor are factors that offer the best outcome from allogeneic transplantation. Current knowledge of, and experience with, non-conventional treatments, such as allogeneic transplantation and gene therapy, are discussed in order to identify the best available treatment and indication for these patients according to their characteristics. At this point in time, when we can see the emergence of \u2018the age of gene therapy\u2019, it is essential to establish the optimal patient setting in which gene therapy can be applied, or better, to define the setting that represents the most suitable indication for gene therapy, identify the patients who should have clinical priority for access to the procedure, and set out requirements and recommendations for the identification of qualified treatment centers for gene therapy. When considering changes to the treatment of patients with \u3b2-TDT, including gene therapy, it is essential that a detailed consultation is held with the patient and their caregiver/family to discuss all possible risks and potential benefits from the treatment. Discussion of this aspect of care is outside of the scope of this document but remains an important element of patient care

CD90 is regulated by notch1 and hallmarks a more aggressive intrahepatic cholangiocarcinoma phenotype

Background: Intrahepatic Cholangiocarcinoma (iCCA) is characterized by a strong stromal reaction playing a role in tumor progression. Thymus cell antigen 1 (THY1), also called Cluster of Differentiation 90 (CD90), is a key regulator of cell–cell and cell–matrix interaction. In iCCA, CD90 has been reported to be associated with a poor prognosis. In an iCCA PDX model, we recently found that CD90 was downregulated in mice treated with the Notch γ-secretase inhibitor Crenigacestat. The study aims to investigate the role of CD90 in relation to the NOTCH pathway. Methods: THY1/CD90 gene and protein expression was evaluated in human iCCA tissues and xenograft models by qRT-PCR, immunohistochemistry, and immunofluorescence. Notch1 inhibition was achieved by siRNA. THY1/CD90 functions were investigated in xenograft models built with HuCCT1 and KKU-M213 cell lines, engineered to overexpress or knockdown THY1, respectively. Results: CD90 co-localized with EPCAM, showing its epithelial origin. In vitro, NOTCH1 silencing triggered HES1 and THY1 down-regulation. RBPJ, a critical transcriptional regulator of NOTCH signaling, exhibited putative binding sites on the THY1 promoter and bound to the latter, implying CD90 as a downstream NOTCH pathway effector. In vivo, Crenigacestat suppressed iCCA growth and reduced CD90 expression in the PDX model. In the xenograft model, Crenigacestat inhibited tumor growth of HuCCT1 cells transfected to overexpress CD90 and KKU-M213 cells constitutively expressing high levels of CD90, while not affecting the growth of HuCCT1 control cells and KKU-M213 depleted of CD90. In an iCCA cohort, patients with higher expression levels of NOTCH1/HES1/THY1 displayed a significantly shorter survival. Conclusions: iCCA patients with higher NOTCH1/HES1/THY1 expression have the worst prognosis, but they are more likely to benefit from Notch signaling inhibition. These findings represent the scientific rationale for testing NOTCH1 inhibitors in clinical trials, taking the first step toward precision medicine for iCCA

DESIGNING OF A RT REAL TIME PCR ASSAY BASED ON NS1 GENE FOR RAPID DETECTION OF USUTU VIRUS (USUV)

Introduction: Usutu virus belongs to the Japanese encephalitis virus group (the isolates exhibited 97% identity) within the family Flaviviridae closely related to West Nile virus (WNV). Both share in nature an enzootic infectious cycle between avian hosts and mosquito vectors (i.e. Culex spp.). The distribution areal is expanding in several European countries, including Italy; the simultaneous spatial and temporal co-circulation of new flaviviruses require a new approaches in the laboratory diagnosis for Flaviviridae infection in humans

Intervenção comunitária para prevenção de acidentes de trânsito entre trabalhadores ciclistas

OBJECTIVE: To evaluate an educational intervention designed to prevent traffic accidents among workers that use the bicycle for commuting. METHODS: A longitudinal intervention study with a stepped wedge implementation was carried out between January 2006 and May 2007. Five neighborhoods with distinct geographic characteristics were selected in the city of Pelotas, Brazil, and 42 census tracts were randomly selected from these neighborhoods. All households were screened for male bicycle commuters, resulting in a sample of 1,133 individuals. The outcomes analyzed were "traffic accidents" and "near accidents". The cyclists were interviewed monthly by phone to record traffic accidents and "near accidents". Every 15 days, from the second month of study, a group of about 60 cyclists was invited to attend the intervention meeting that included an educational component (a talk and a video presentation), distribution of a safety kit (reflective belt & sash, reflective tape and an educational booklet) and a bicycle breaks check-up (maintenance performed if necessary). Poisson regression adjusted for time effect was used to assess the intervention effect. RESULTS: Nearly 45% of the cyclists did not attend the intervention. During the study period, 9% of the study individuals reported a traffic accident and 88% reported a "near accident". In total there were 106 accidents and 1,091 near accidents. There was no effect observed from the intervention on either of the outcomes. CONCLUSIONS: The intervention tested was not capable of reducing traffic accidents among bicycle commuters. Lack of interest in safety by commuters and external factors, such as road design and motorist behavior, may have together influenced this result.OBJETIVO: Evaluar una intervención educacional de prevención de accidentes de tránsito con trabajadores que utilizan la bicicleta como modo de transporte. MÉTODOS: Estudio de intervención, longitudinal, con implementación escalonada, realizado en cinco urbanizaciones con características geográficas distintas en la ciudad de Pelotas, Sur de Brasil, de enero de 2006 a mayo de 2007. Fueron sorteados 42 sectores censados de dichas urbanizaciones. Todos los domicilios fueron visitados en búsqueda de trabajadores del sexo masculino que utilizasen la bicicleta como modo de transporte, resultando en una muestra de 1.133 individuos. Fueron analizados como resultados "accidentes de tránsito" y "casi-accidentes". Mensualmente, vía telefónica, los ciclistas eran interrogados con respecto a la ocurrencia de accidentes de tránsito y de "casi-accidentes". Quincenalmente, a partir del segundo mes de acompañamiento, un grupo de aproximadamente 60 ciclistas era convidado a participar de la intervención, que incluía un componente educativo (seminario y presentación de video educativo), distribución de un kit de seguridad (chaleco nocturno con reflexivo, cartilla educativa y cintas reflexivas) y revisión de los frenos de la bicicleta (mantenimiento realizado al ser necesario). Regresión de Poisson, con ajuste para el efecto del tiempo, fue utilizada para medir el efecto de la intervención. RESULTADOS: Aproximadamente 45% de los ciclistas no comparecieron a la intervención. Durante el período de estudio, 9% de los individuos informaron un accidente de tránsito y 88% un casi-accidente. En total, ocurrieron 106 accidentes y 1.091 casi-accidentes. No fue observado efecto de la intervención en ambos resultados. CONCLUSIONES: La intervención propuesta no fue capaz de reducir accidentes entre trabajadores ciclistas. falta de interés en seguridad por parte de los ciclistas y factores externos, tales como infra-estructura de las vías y comportamiento de los choferes, pueden haber colaborado para ese resultado.OBJETIVO: Avaliar uma intervenção educacional de prevenção de acidentes de trânsito com trabalhadores que utilizam a bicicleta como modo de transporte. MÉTODOS: Estudo de intervenção, longitudinal, com implementação escalonada, realizado em cinco bairros com características geográficas distintas na cidade de Pelotas, RS, de janeiro de 2006 a maio de 2007. Foram sorteados 42 setores censitários desses bairros. Todos os domicílios foram visitados em busca de trabalhadores do sexo masculino que utilizassem a bicicleta como modo de transporte, resultando em uma amostra de 1.133 indivíduos. Foram analisados como desfechos "acidentes de trânsito" e de "quase-acidentes". Mensalmente, via telefone, os ciclistas eram questionados a respeito da ocorrência de acidentes de trânsito e de "quase-acidentes". Quinzenalmente, a partir do segundo mês de acompanhamento, um grupo de aproximadamente 60 ciclistas era convidado a participar da intervenção, que incluía um componente educativo (palestra e apresentação de vídeo educativo), distribuição de um kit de segurança (colete noturno refletivo, cartilha educativa e fitas refletivas) e revisão dos freios da bicicleta (manutenção realizada se necessário). Regressão de Poisson, com ajuste para o efeito do tempo, foi utilizada para medir o efeito da intervenção. RESULTADOS: Aproximadamente 45% dos ciclistas não compareceram à intervenção. Durante o período do estudo, 9% dos indivíduos informaram um acidente de trânsito e 88%, um quase-acidente. No total, ocorreram 106 acidentes e 1.091 quase-acidentes. Não foi observado efeito da intervenção em ambos os desfechos. CONCLUSÕES: A intervenção proposta não foi capaz de reduzir acidentes entre trabalhadores ciclistas. Falta de interesse em segurança por parte dos ciclistas e fatores externos, tais como infra-estrutura das vias e comportamento dos motoristas, podem ter colaborado para esse resultado