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The wood mouse Apodemus sylvaticus is common in woodlands and open areas of the Western Palearctic. Despite extensive research, little is known about its population ecology in fields in the Mediterranean area, where the climate involves great seasonal changes in environmental features. Here, we investigated wood mice seasonal fluctuations in the number of captures and population structure by sampling long-fallow fields and woodlands, i.e., oak forest and conifer plantation, in a heterogeneous landscape of central Italy. Mice were live-trapped every two months for three years (23.814 trap-days). The number of captures, mice body weight, and proportion of adult, residents and breeding individuals were analyzed. Mice dynamics changed across seasons and habitats. In fields, we recorded more captures, more reproductive individuals, and fewer non-adults and resident individuals in the warmer months compared to the colder months; mice were heavier in warmer months. During the cold season, the captures and adult proportion in fields were lower than in resource-rich woodlands. Breeding and non-resident mice were more abundant in fields than in woodlands in warmer months. Overall, the seasonal demographic variations we recorded provide evidence that fields can represent a suboptimal habitat in Mediterranean heterogeneous landscapes, acting nonetheless as a source of food resources, cover, and mates for mice in spring–summer.

The wood mouse Apodemus sylvaticus is common in woodlands and open areas of Western Palearctic. Despite extensive research, little is known about its population ecology in fields in the Mediterranean area, where climate involves great seasonal changes in environmental features. Here, we investigated wood mice seasonal fluctuations in abundance and population structure by sampling long-fallow fields and two woodland types, i.e. oak forest and conifer plantation, in a heterogeneous landscape of central Italy. Mice were live-trapped in three sites per habitat type, every other month for three years (23.814 trap-days). Population abundance, age structure, mice body weight and proportion of residents and breeding individuals were analysed. Sampling effort resulted in 350 captures of 245 individuals. Mice dynamics changed across seasons and habitats. In fields, we recorded more captures, more reproductive individuals, and fewer immature and resident individuals in warmer than in colder months; mice were heavier in warmer months. These results suggest that fields may better suit the species ecological requirements (i.e. food and cover resources) in spring-summer, representing a seasonally suboptimal habitat for mice. Population abundance in fields was lower than in woodlands during the cold season, when immatures were more frequent in fields than in resource-rich woodlands. Conversely, breeding and non-resident mice were more abundant in fields than in woodlands in warmer months. Overall, the seasonal demographic variations we recorded evidence that fields can represent a suboptimal habitat in Mediterranean heterogeneous landscapes and can nonetheless act as a source of resources, mates and space for mice in spring-summer.

Strong mutual relationships exist between rodents and ecosystems. By modifying the structure and functioning of ecosystems, human activity can affect rodent behaviour and ecology. The yellow-necked mouse Apodemus flavicollis is widespread in Europe, and its spatial ecology has been studied in various habitats, but studies are lacking for Mediterranean forests often altered by forest management practices. We investigated the spatial behaviour of A. flavicollis in a sub-Mediterranean deciduous oak forest of central Italy subject to forest management. We radio-tracked 27 individuals in two different coppice stands, i.e. a recently cut area and a high forest, differing in terms of species-specific habitat quality and rodent population density. We analysed the size of home ranges in relation to habitat type and sex. Our results revealed that home range and core area size did not differ between habitat types or sexes. The spatial behaviour of A. flavicollis thus did not appear to be influenced by population density and habitat quality. The lack of sex-related differences confirms the current knowledge on the species’ spatial ecology. Our findings provide the first useful information on the spatial behaviour of A. flavicollis in sub-Mediterranean deciduous oak forests, whose ecological processes may be markedly influenced by this key species at several trophic levels.

The assessment of well-being remains an important topic for many disciplines including medical, psychological, social, educational, and economic fields. The present study assesses the reliability and validity of a five-item instrument for evaluating physical, psychological, spiritual, relational, and general well-being. This measure uniquely utilizes a segmented numeric version of the visual analog scale in which a respondent selects a whole number that best reflects the intensity of the investigated characteristic. In study one, 939 clinical (i.e., diagnosed with cancer and liver disease with cirrhosis) and non-clinical (i.e., undergraduate students and their family and acquaintances) participants between the ages of 18 to 87 years (M= 47.20 years,SD= 19.62, 54% males) were recruited. Results showed items have strong discriminant ability and the spread of threshold parameters attests to the appropriateness of the response categories. Moreover, convergent and discriminant validity were found with other self-report measures (e.g., depression, anxiety, optimism, well-being) and the measure showed responsiveness to two separate interventions for clinical populations. In study two, 287 Canadian (ages ranged from 18 to 30 years;M= 20.78,SD= 3.32; 23% males) and 342 Italian undergraduate psychology students (age ranged from 18 to 29 years,M= 21.21 years,SD= 1.73, 38% males) were recruited to complete self-report questionnaires. IRT-based differential item functioning analyses provided evidence that the item properties were similar for the Italian and English versions of the scale. Additionally, the validity results obtained in study one were replicated and similar relationships between criterion variables were found when comparing the Italian- and the English-speaking samples. Overall, the current study provides evidence that the Italian and English versions of the WB-NRSs offer added value in research focused on well-being and in assessing well-being changes prompted by intervention programs.

Information on intra- and inter-specific social tolerance is useful to evaluate the role of social interactions at shaping population dynamics. This is particularly interesting for sympatric species with similar ecological requirements that can be potential competitors. In this light, we investigated multiple captures of Apodemus flavicollis, A. sylvaticus and Myodes glareolus constituting a guild of forest- and ground-dwelling rodents in central Italy. Small mammals were live-trapped every other month for four years. Multiple captures made up 3% of total captures, with a very similar occurrence in all three species. In each species the number of multiple captures increased with both population density and amount of caught con-specifics. Individuals of the same species were caught together in 85% of multiple captures. In all three species, sexually active individuals were also involved in homosexual and interspecific multiple captures, suggesting that multiple captures are not primarily caused by reproductive behaviour. The occurrence of intra- and inter-specific captures and the absence of injury signs in individuals trapped together suggest social tolerance and support the hypothesis of weak competitive interactions between these species constituting a guild of rodents in this sub-Mediterranean deciduous oak forest. As multiple capture events can occur during live trapping, we stress the importance of utilising this secondary data to gain useful information on social factors influencing small mammal populations.

Abstract. The present study aimed at evaluating if the three-item sense of coherence (SOC) scale developed by Lundberg and Nystrom Peck (1995) can be effectively used for research purpose in both nonclinical and clinical samples. To provide evidence that it represents adequately the measured construct we tested its validity in a nonclinical (N = 658) and clinical sample (N = 764 patients with cancer). Results obtained in the nonclinical sample attested a positive relation of SOC – as measured by the three-item SOC scale – with Antonovsky’s 13-item and 29-item SOC scales (convergent validity), and with dispositional optimism, sense of mastery, anxiety, and depression symptoms (concurrent validity). Results obtained in the clinical sample confirmed the criterion validity of the scale attesting the positive role of SOC – as measured by the three-item SOC scale – on the person’s capacity to respond to illness and treatment. The current study provides evidence that the three-item SOC scale is a valid, low-loading, and time-saving instrument for research purposes on large sample.

The present study aims at quantifying the error in visual sexing of live-trapped bank voles and evaluating if animal body weight and experience of field workers affected the ability to determine the sex of voles. The error in sex attribution involved 25.6% of non-reproductive individuals, pointing out the need to validate the field sex identification. Body weight of voles did not affect the ability of trappers to visually discriminate the sex of animals. Field workers had similar percentages of error independently of their expertise in vole sexing but they also showed a sex-bias in wrongly sexed individuals.

Having a thorough understanding of animal feeding behaviour is a basic aim in ecology. Food represents a crucial resource that can strongly rule animal populations, especially where food supplies are seasonal, such as in temperate areas. In Italy, sub-Mediterranean forests dominated by deciduous oaks are commonly inhabited by the yellow-necked mouse Apodemus flavicollis, the wood mouse A. sylvaticus and the bank vole Myodes glareolus. Despite the rich literature regarding their diet composition in northern Europe, to our knowledge no studies have been published on food preferences of these rodents in syntopy in sub-Mediterranean deciduous forests. Feeding preferences of 33 A. flavicollis, 10 A. sylvaticus and 18 M. glareolus on reproductive parts (flowers, unripe and ripe fruits) of 26 representative plant species in a deciduous oak forest of central Italy were investigated through seasonal cafeteria-style experiments. Our findings evidence that A. flavicollis exhibited distinct preferences in all seasons...

“In the mirror of the Wonder of Luca Giordano” was a multi-sensorial experience created in the gallery frescoed by Luca Giordano in Palazzo Medici Riccardi, in Florence; the project involved different disciplines and researchers. The entire experience was subjected to an impact analysis, combining principally psycho-physiological, qualitative psychological and neuro-physiological aspects. In most of the visitors who participated in the study the experience evoked a sense of pleasure, enjoyment, relaxation, lightness, space-time suspension, involvement and immersiveness. In many of the visitors, the devices detected changes in heartbeat with a stastically significant decrease in blood pressure and heart rate, demontrating that the impact of artwork in a multi-sensorial experience and in an augmented perception environment is a psycho-somatic impact. Our experience suggests that projects such as "In the mirror of the Wonder of Luca Giordano" could be a very useful tool for cultivating emotional intelligence and could be developed in museums alongside the more classical paths of fruition.

Purpose: Although an optimal goal remains the routine assessment of unmet needs of all patients with cancer, particular attention should be paid to those groups of patients with characteristics known to be more frequently associated with unmet needs in general or with specific areas of need. This report aims to describe the sociodemographic, clinical, and psychological characteristics associated with higher unmet needs in Italian cancer patients. Methods: A total of 835 cancer patients from different care settings (ward, day hospital, follow-up ambulatory, rehabilitation unit, and palliative care) filled out the Needs Evaluation Questionnaire (NEQ), the Psychological Distress Inventory, and the Sense of Coherence Scale. Association of NEQ scores with the clinical and demographic variables were tested using analysis of variance. Results: Higher NEQ total score was associated with lower educational level, inpatient care setting, radiotherapy treatment, psychological distress, and lower resilience trait sense of coherence. Different predictors were identified for different areas of unmet needs. Care setting, psychological distress, and resilience trait were the strongest indicators of unmet needs in every area: information/communication, assistance/care, material needs, relational needs, and psychoemotional support. Conclusions: Clinicians should consider that inpatients with a high distress and a low resilience trait sense of coherence represent a group of cancer patients to be investigated with particular attention regarding unmet needs.

Several studies regarding acorn choice by granivorous rodents have been conducted in dry Mediterranean oak forests, mainly composed by evergreen oaks. However, a lack of knowledge still persists about this subject in sub-Mediterranean forests dominated by deciduous oaks. We investigated the choice between Quercus cerris and Q. pubescens acorns by terrestrial small mammals in a deciduous oak forest of Central Italy, dominated by Q. cerris. Using a cafeteria-style feeding experiment, we tested 14 Apodemus flavicollis, and 10 Myodes glareolus. Animals were kept in outdoor experimental enclosures and given simultaneously a sample of acorns of the two oak species collected in situ. All seeds were sound and of the same size, shape and weight. Seed consumption was checked regularly, to record the percentage of consumed acorn sample. To evaluate a possible influence of pericarp on choice, acorns were presented both whole and shelled. Biochemical composition of seeds was analysed. Acorns of both oaks were similar ...

Objective Although many studies indicate that the use of complementary and alternative medicine by cancer patients is common and widespread, few studies have focused on unmet needs of patients using complementary therapies (CTs). The aim of the present study was to evaluate, through a quantitative approach, possible associations between the use of CTs and the presence of specific unmet needs in cancer patients. Methods In six Italian oncology departments, 783 patients were interviewed about CTs use and completed the Needs Evaluation Questionnaire. Patients included in the study had different primary tumor sites and were in different phases of the disease and care process. Results At the time of the survey, 38.3% of patients were using one or more types of CTs. According to Needs Evaluation Questionnaire, the use of CTs was associated (p

Purpose: Assessing patients’ unmet supportive care needs is essential in order to prioritize areas of cancer care that require improvement. The aim of the present cross-sectional study was to compare the unmet needs of cancer patients in different stages of the disease and care process (diagnosis, treatments following diagnosis, follow-up and/or rehabilitation, relapse/recurrence, progression of the disease, and palliative care). Methods: The research focused on patients from 7 oncology units of the same geographic region (Tuscany, a region of central Italy) in the same period of time regardless of primary tumor site. A total of 752 patients filled in the Needs Evaluation Questionnaire and the Psychological Distress Inventory. Results: We observed high rates of cancer patients who expressed unmet needs, especially in the areas of information and relational and material needs. The multiple regression models showed a direct correlation between psychological distress and extent of unmet needs. Individual unmet needs had significantly different entities at diverse phases. Conclusions: The present study confirmed the dynamic nature of needs of cancer patients, highlighting some critical aspects in different stages of the care process on which to concentrate attention and resources and suggesting the usefulness of periodic and repeated assessments of principal needs.

Objective:The present study intended to evaluate the impact of a standardized format—called the “Music Givers,” based on a single session of music intervention followed by a buffet—on the psychological burden and well-being of hospitalized cancer patients.Method:The Distress Thermometer (DT), the Hospital Anxiety and Depression Scale (HADS), and self-reported visual analogue scales (score range = 1–10) to assess pain, fatigue, and five areas of well-being (i.e., physical, psychological, relational, spiritual, and overall well-being) were administered to 242 cancer patients upon admission to and at discharge from the hospital. Among them, 103 were hospitalized during which time a live concert took place (intervention group), whereas 139 patients were hospitalized when it did not (control group).Results:Compared to the control group, patients in the intervention group demonstrated less distress at discharge according to the DT (adjusted estimate of difference = –0.8,p = 0.001), lower HADS–Anxiety (–1.7,p p = 0.001), and higher scores on all the well-being scales, with the exception of spiritual well-being. In addition, no between-group differences were found in terms of pain and fatigue scores at discharge.Significance of results:The one-session format of the Music Givers intervention is an effective, standardized, easy-to-replicate, and low-cost intervention that reduces psychological burden and improves the well-being of hospitalized cancer patients. Listening to live music and the opportunity to establish better relationships between patients and staff could explain these results.

The Needs Evaluation Questionnaire (NEQ) is a self-administered instrument used in oncology clinical practice and research. Objective The main aim of this study was to provide evidence of the broad employability of the NEQ with patients of different gender and age with cancer in different phases of the disease and care process, using an Item Response Theory (IRT) approach and investigating Differential Item Functioning (DIF). Methods The NEQ was completed by 762 patients visiting, consecutively, outpatient clinics or admitted to oncology wards. Patients included in the study had different primary tumor sites and were in different phases of the disease and care process. The properties of the questionnaire were analyzed by applying IRT to test how well each item of the scale concurs in measuring unmet needs, how reliable the whole scale is, and whether the scale was metrically invariant across gender, age, and phase of the disease. Results Results showed that the NEQ performed well in measuring unmet needs and measurement equivalence of the scale across gender, age, and phase of the disease was verified. Conclusions The current study supports the utility and broad employability of the NEQ, thus providing empirical evidence that it is psychometrically sound and metrically equivalent across different groups of cancer patients. As such, the scale could be an effective tool when planning psychosocial interventions to improve the care process and patients’ quality of life.

Context In Italy, data regarding the use of complementary therapies (CTs) among patients with cancer are sparse and discordant. Objectives The present study aimed to investigate the demographic and psychological characteristics of Italian cancer patients who use CTs and the perceived benefit of users. Methods Eight hundred three patients from six Italian oncology departments were interviewed about CT use and completed two questionnaires to explore psychological distress and the resilience trait called sense of coherence (SOC). Patients included in the study had different primary tumor sites and were in different phases of the disease and care process. Results At the time of measurement, 37.9% of patients were using one or more types of CTs. The most commonly used CTs were diets and dietary supplements (27.5%), herbs (10.8%), homeopathy (6.4%), and mind-body therapies (5.5%). The Italian context is characterized by a high percentage of patients who informed their physicians about CT use (66.3%) and who experienced benefits (89.6%); 75.2% of the patients had used CTs in the past. Multivariate analysis revealed that young, female patients, who previously used complementary and alternative medicine in the past, appear more likely to use at least one type of CT in the present. Predictors of the use of CTs varied according to the type of CT. Among psychological factors, SOC was positively associated with both past and present CT use. Conclusion Overall prevalence of CTs among Italian cancer patients is high and is in accordance with the European average. In addition to clinical and sociodemographic factors, the resilience trait SOC also was associated with CT use.

In Italy a new experience of music medicine called “The Music Givers” is spreading among Oncology Units; it aims to organise weekly live concerts (length 45–60 min) followed by a buffet. Purpose of the present study is to evaluate the effect of the format of The Music Givers on cancer in-patients' anxiety. State-Trait Anxiety Inventory (STAI-Y) was administered to 111 in-patients before and after the concerts. After the concerts we observed a 3.87 point decrease in state anxiety (p

An interlocking system monitors the status of the objects in a railway yard, allowing or denying the movement of trains, in accordance with safety rules. The high number of complex interlocking rules that guarantee the safe movements of independent trains in a large station makes the verification of such systems a complex task, which needs to be addressed in conformance with EN50128 safety guidelines. In this paper we show how the problem has been addressed by a manufacturer at the final validation stage of production interlocking systems, by means of a model extraction procedure that creates a model of the internal behaviour, to be exercised with the planned test suites, in order to reduce the high costs of direct validation of the target system. The same extracted model is then subject to formal verification experiments, employing an iterative verification process implementing slicing and CEGAR-like techniques, defined to address the typical complexity of this application domain.

Objective: The evaluation of psychological distress in cancer patients recently entered oncologic clinical practice. The objective of this study was to evaluate the role of clinical interview within psycho-oncologic assessment. Methods: Questionnaires assessing distress (PDI), psychopathology (MHQ, HADS) and needs (NEQ) and a subsequent clinical interview were proposed to 320 consecutive inpatients from the Oncology Department of Careggi Hospital in Florence. Results: The clinical interview made it possible to evaluate a significant percentage of patients (30%) who did not fill in questionnaires and to detect the presence of distress in 39 (13.7%) patients who would not have received a diagnosis in a protocol for the assessment of distress based only on questionnaires. It also provided the possibility to ask for help or to receive clinical support to a high percentage of patients (44.1%) who had not requested to speak to a psychologist through the questionnaires (NEQ). Moreover, 25% of patients who received prolonged clinical support had a low score in tests detecting distress, indicating that the opportunity for therapeutic support can emerge during a clinical interview, also in the absence of relevant symptoms detected by questionnaires. Conclusions: The use of more than one questionnaire in the assessment of distress and psychopathology is associated with reduced compliance and redundant information. On the other hand, clinical interview has a pivotal role in clinical evaluation and access to psychological support. We conclude that optimal efficacy of programs assessing distress in cancer patients is reached when a single questionnaire evaluating distress is associated with a clinical interview. Copyright © 2010 John Wiley & Sons, Ltd.

Hepatic stellate cells (HSC) coordinate the liver wound-healing response through secretion of several cytokines and chemokines, including CCL2 (formerly known as monocyte chemoattractant protein-1). In this study, we evaluated the role of different proteins of the MAPK family (ERK, p38MAPK, and JNK) in the regulation of CCL2 expression by HSC, as an index of their proinflammatory activity. Several mediators activated all three MAPK, including TNF, IL-1, and PDGF. To assess the relative role of the different MAPKs, specific pharmacological inhibitors were used; namely, SB203580 (p38MAPK), SP600125 (JNK), and PD98059 (MEK/ERK). The efficacy and specificity of the different inhibitors in our cellular system were verified analyzing the enzymatic activity of the different MAPKs using in vitro kinase assays and/or testing the inhibition of phosphorylation of downstream substrates. SB203580 and SP600125 dose-dependently inhibited CCL2 secretion and gene expression induced by IL-1 or TNF. In contrast, inhibition of ERK did not affect the upregulation of CCL2 induced by the two cytokines. Finally, activin A was also found to stimulate CCL2 expression and to activate ERK, JNK, p38, and their downstream targets. Unlike in cells exposed to proinflammatory cytokines, all three MAPKs were required to induce CCL2 secretion in response to activin. We conclude that members of the MAPK family differentially regulate cytokine-induced chemokine expression in human HSC.

Background & aims: The chemokines CCL19 and CCL21 bind CCR7, which is involved in the organization of secondary lymphoid tissue and is expressed during chronic tissue inflammation. We investigated the expression of CCL21 and CCR7 in chronic hepatitis C. The effects of CCL21 on hepatic stellate cells (HSCs) were also studied. Methods: Expression of CCL21 was assessed by in situ hybridization and immunohistochemistry. CCR7 on T cells was analyzed by flow cytometry. Cultured human HSCs were studied in their activated phenotype. Results: In patients with chronic hepatitis C, expression of CCL21 and CCR7 was up-regulated. CCL21 was detected in the portal tracts and around inflammatory lymphoid follicles, in proximity to T lymphocytes and dendritic cells, which contributed to expression of this chemokine. Expression of CCR7 was also increased in patients with primary biliary cirrhosis. Intrahepatic CD8 + T lymphocytes isolated from patients with chronic hepatitis C had a significantly higher percentage of positivity for CCR7 than those from healthy controls, and the expression of CCR7 was associated with that of CXCR3. Cultured HSCs expressed functional CCR7, the activation of which stimulated cell migration and accelerated wound healing in an in vitro model. Exposure of HSCs to CCL21 triggered several signaling pathways, including extracellular signal-regulated kinase, Akt, and nuclear factor κB, resulting in induction of proinflammatory genes. Conclusions: Expression of CCL21 during chronic hepatitis C is implicated in the recruitment of T lymphocytes and the organization of inflammatory lymphoid tissue and may promote fibrogenesis in the inflamed areas via activation of CCR7 on HSCs.

The first private chapel for which the Pope granted permission in the middle of the fifteenth century, in Palazzo Medici in Florence, frescoed with the Procession of the Magi by Benozzo Gozzoli, has recently become the setting for an experience of guided perception with the support of multimedia technologies and augmented reality in the workshop “Procession in time through to the splendour of the interior epiphany”. The research detects the psychophysiological responses induced by immersion in an enriched environment.

An interlocking system monitors the status of the objects in a railway yard, allowing or denying the movement of trains, in accordance with safety rules. These rules depend on the topology of the station and hence every single delivered system obeys a particular set of rules. On the other hand, being safety critical systems, interlocking are subject to expensive certification processes. Part of these costs are due to the fact that testing has to be repeated for each delivered product, moreover, due to the complexity of such topologies, the test suites may be very large, and different for each product. In this paper we show how the problem has been addressed at the final validation stage of production interlocking systems, by extracting a model of the implemented interlocking logic from the on-target description of the topology. This model is exercised with the planned test suite. Since simulation appears to be more than an order of magnitude faster than testing the target, early discovery of bugs in the description of rules or of inaccuracies in the test suite can spare hours of rework on the target.

BackgroundDying at home and dying at the preferred place of death are advocated to be desirable outcomes of palliative care. More insight is needed in their usefulness as quality indicators. Our objective is to describe whether "the percentage of patients dying at home" and "the percentage of patients who died in their place of preference" are feasible and informative quality indicators.Methods and findingsA mortality follow-back study was conducted, based on data recorded by representative GP networks regarding home-dwelling patients who died non-suddenly in Belgium (n = 1036), The Netherlands (n = 512), Italy (n = 1639) or Spain (n = 565). "The percentage of patients dying at home" ranged between 35.3% (Belgium) and 50.6% (The Netherlands) in the four countries, while "the percentage of patients dying at their preferred place of death" ranged between 67.8% (Italy) and 86.0% (Spain). Both indicators were strongly associated with palliative care provision by the GP (odds ratios of 1.55-13.23 and 2.30-6.63, respectively). The quality indicator concerning the preferred place of death offers a broader view than the indicator concerning home deaths, as it takes into account all preferences met in all locations. However, GPs did not know the preferences for place of death in 39.6% (The Netherlands) to 70.3% (Italy), whereas the actual place of death was known in almost all cases.ConclusionGPs know their patients' actual place of death, making the percentage of home deaths a feasible indicator for collection by GPs. However, patients' preferred place of death was often unknown to the GP. We therefore recommend using information from relatives as long as information from GPs on the preferred place of death is lacking. Timely communication about the place where patients want to be cared for at the end of life remains a challenge for GPs.

Railway interlocking systems still represent a challenge for formal verification by model checking: the high number of complex interlocking rules that guarantee the safe movements of independent trains in a large station makes the verification of such systems typically incur state space explosion problems. In this paper we describe a study aimed to define a verification process based on commercial modelling and verification tools, for industrially produced interlocking systems, that exploits an appropriate mix of environment abstraction, slicing and CEGAR-like techniques, driven by the low-level knowledge of the interlocking product under verification, in order to support the final validation phase of the implemented products. © 2014 Springer International Publishing.

Notwithstanding the large amount of attempts to formally verify them, railway interlocking systems still represent a challenging problem for automatic verification. Interlocking systems controlling sufficiently large stations, due to their inherent complexity related to the high number of variables involved, are not readily amenable to automatic verification, typically incurring in state space explosion problems. The study described in this paper aims at evaluating and experimenting the industrial application of verification by model checking for this class of systems. The choices made at the beginning of the study, also on the basis of specific requirements from the industrial partner, are presented, together with the advancement status of the project and the plans for its completion.

Hepatic stellate cells (HSC) and glomerular mesangial cells (MC) are tissue-specific pericytes involved in tissue repair, a process that is regulated by members of the chemokine family. In this study, we explored the signal transduction pathways activated by the chemokine receptor CXCR3 in vascular pericytes. In HSC, interaction of CXCR3 with its ligands resulted in increased chemotaxis and activation of the Ras/ERK cascade. Activation of CXCR3 also stimulated Src phosphorylation and kinase activity and increased the activity of phosphatidylinositol 3-kinase and its downstream pathway, Akt. The increase in ERK activity was inhibited by genistein and PP1, but not by wortmannin, indicating that Src activation is necessary for the activation of the Ras/ERK pathway by CXCR3. Inhibition of ERK activation resulted in a decreased chemotactic and mitogenic effect of CXCR3 ligands. In MC, which respond to CXCR3 ligands with increased DNA synthesis, CXCR3 activation resulted in a biphasic stimulation of ERK activation, a pattern similar to the one observed in HSC exposed to platelet-derived growth factor, indicating that this type of response is related to the stimulation of cell proliferation. These data characterize CXCR3 signaling in pericytes and clarify the relevance of downstream pathways in the modulation of different biologic responses.

We report the experience of the validation team of a railway signalling company when addressing the problem of testing an equipment configuration tool. The two contrasting issues that add to the complexity of the task are: the tool includes a Graphical User Interface built on standard windowing systems, and the configuration produced by the tool, when loaded on the equipment, has a potential impact on the safety of the overall signalling system. This has required a particular care in the choice of testing techniques and of test case selection strategies, however confronting with actual cost and feasibility constraints.

Background and Aim Spiritual life can be defined as the search for personal contact with the transcendent. Careful assessment of spiritual life can help to value its importance to cancer patients from the moment of their diagnosis. Methods This is a cross-sectional study. Two hundred fifty-seven patients undergoing cancer treatment filled in the validated Italian version of the Systems of Belief Inventory (SBI-15R). Patients were also asked to attribute themselves to one of the following, mutually exclusive categories: believer and churchgoer, believer but no churchgoer, and non-believer. Results Five patients did not report their religious stance and were therefore excluded from the analysis. Of the remaining 252 patients, 49% declared to be believers and churchgoers, 43% believers but not churchgoers, and 8% non-believers. Of the 20 cancer patients who declared not to have a religious faith, 7 patients agreed with the statement that they felt certain that God exists in some form, and 4 had experienced peace of mind through prayer and meditation. Almost all of the patients who declared to have a religious faith and to be churchgoers explicitly affirmed to have been helped by prayer and meditation in coping with their illness. Among believer churchgoers, only 30% declared to seek out the religious or spiritual community when they needed help. Conclusions A large proportion of cancer patients find themselves involved with the search for a personal contact with the transcendent, also beyond any specific religious affiliation. These spiritual issues may be important even when they are not expressed as participation in religious rituals or adherence to specific religious beliefs. On the other hand, participation in religious rituals often implies the need for a personal spiritual life, both through those rituals and beyond them, as through personal prayer and meditation. These results ask for more attention on the part of professionals towards spiritual resources among cancer patients. It might be appropriate to look systematically for these resources from the moment of the diagnosis, through the sensitive administration of an easy and valid assessment tool like the SBI-15R.

Background There is an increase in the attention to factors influencing the quality of life of cancer patients. The aim of the present study was to evaluate temperament and character traits related to health-related quality of life (HRQoL) in patients with cancer. Methods Two hundred and three inpatients from three Italian oncology departments filled in the Temperament Character Inventory (TCI-140) based on Cloninger's personality model, the SF-36 questionnaire assessing HRQoL, and the Hospital Anxiety and Depression Scale (HADS). Eighty percent of patients were undergoing chemotherapy. Results Lower levels of harm avoidance and higher levels of self-directedness were significantly correlated with a better HRQoL. Regression analysis controlling for psychopathology (anxiety and depression symptoms) showed that the influence of temperament and character traits on quality of life seemed to add little to the influence of psychopathology. Conclusions The present study demonstrates the existence of some relations between HRQoL and temperament and character traits assessed using the TCI-140 questionnaire. However, among the psychological factors, psychopathology seems to retain more influence on HRQoL of cancer patients.

The liver represents a site of expression of neurotrophins and their receptors. We have characterized the expression and intracellular localization of the nerve growth factor (NGF) receptor, Trk-A, in liver cells in vivo and in vitro. In both normal and fibrotic liver tissue, Trk-A immunostaining was present in different cell types, including parenchymal cells and cells of the inflammatory infiltrate. In hepatocytes and activated stellate cells (HSC), Trk-A showed a predominant nuclear localization, both in the presence and absence of injury. In cultured HSC, Trk-A was found to be functional, because exposure of the cells to recombinant NGF resulted in stimulation of cell migration and activation of intracellular signaling pathways, including Ras-ERK and PI3K/Akt. Remarkably, in cultured HSC, Trk-A staining was found constitutively in the nucleus. In these cells, Trk-A could be stained only by antibodies directed against the intracellular domain but not by those recognizing the extracellular portion of Trk-A suggesting that the intracellular portion of the receptor is the major determinant of nuclear Trk-A staining. In contrast to HSC, freshly isolated hepatocytes did not show any nuclear localization of the intracellular portion of Trk-A. In pheocromocytoma cells, nuclear staining for Trk-A was not present in conditions of serum deprivation, but could be induced by exposure to NGF or to a mixture of soluble mediators. We conclude that nuclear localization of the intracellular domain of Trk-A is observed constitutively in liver cells such as HSC, while in other cell types it could be induced in response to soluble factors.

Thrombopoietin (TPO), a cytokine that participates in the differentiation and maturation of megakaryocytes, is produced in the liver, but only limited information is available on the biological response of liver-derived cells to TPO. In this study, we investigated whether HepG2 cells express c-Mpl, the receptor for TPO, and whether TPO elicits biological responses and intracellular signaling in this cell type. Specific transcripts for c-Mpl were detected in HepG2 cells by RT-PCR, and expression of the protein was demonstrated by Western blot analysis and immunofluorescence. Exposure of HepG2 cells to TPO was associated with a dose-dependent increase in cell migration and chemoinvasion through Matrigel-coated filters. A checkerboard analysis showed that the effects of TPO on cell migration were dependent on both chemotaxis and chemokinesis. Exposure of HepG2 cells to TPO resulted in the activation of different members of the MAPK family, including ERK and JNK, as assessed using phosphorylation-specific antibodies and immune complex kinase assays. TPO also activated phosphatidylinositol 3-kinase (PI3K) and the downstream kinase Akt in a time-dependent manner. Finally, activation of c-Mpl was associated with increased activation of nuclear factor-κB. With the use of specific inhibitors, tyrosine phosphorylation and activation of PI3K were found to be required for the induction of migration in response to TPO. We conclude that TPO exerts biological actions on cultured hepatoblastoma cells via activation of c-Mpl and its downstream signaling.

The chemokines CCL19 and CCL21 bind CCR7, which is involved in the organization of secondary lymphoid tissue and is expressed during chronic tissue inflammation. We investigated the expression of CCL21 and CCR7 in chronic hepatitis C. The effects of CCL21 on hepatic stellate cells (HSCs) were also studied.Expression of CCL21 was assessed by in situ hybridization and immunohistochemistry. CCR7 on T cells was analyzed by flow cytometry. Cultured human HSCs were studied in their activated phenotype.In patients with chronic hepatitis C, expression of CCL21 and CCR7 was up-regulated. CCL21 was detected in the portal tracts and around inflammatory lymphoid follicles, in proximity to T lymphocytes and dendritic cells, which contributed to expression of this chemokine. Expression of CCR7 was also increased in patients with primary biliary cirrhosis. Intrahepatic CD8(+) T lymphocytes isolated from patients with chronic hepatitis C had a significantly higher percentage of positivity for CCR7 than those from healthy controls, and the expression of CCR7 was associated with that of CXCR3. Cultured HSCs expressed functional CCR7, the activation of which stimulated cell migration and accelerated wound healing in an in vitro model. Exposure of HSCs to CCL21 triggered several signaling pathways, including extracellular signal-regulated kinase, Akt, and nuclear factor kappaB, resulting in induction of proinflammatory genes.Expression of CCL21 during chronic hepatitis C is implicated in the recruitment of T lymphocytes and the organization of inflammatory lymphoid tissue and may promote fibrogenesis in the inflamed areas via activation of CCR7 on HSCs.

Activated hepatic stellate cells (HSC) regulate the liver "wound-healing" response through expression of chemokines, including monocyte chemoattractant protein-1 (MCP-1), which participate in the formation of the inflammatory infiltrate during liver injury. Cyclooxygenase (COX) catalyzes the conversion of arachidonic acid into prostaglandins, which may contribute to the inflammatory response. In this study, we investigated the effects of COX inhibitors on the expression of MCP-1 in cultured HSC. Pretreatment of HSC with nonspecific COX inhibitors such as indomethacin or ibuprofen markedly reduced the expression of MCP-1 caused by exposure to tumor necrosis factor alpha (TNF-alpha) or interleukin-1alpha (IL-1alpha). NS-398, a specific COX-2 inhibitor, also resulted in a dose-dependent inhibition of MCP-1 gene and protein expression. These effects were dependent on reduced MCP-1 transcription, as established using a reporter plasmid. In contrast, the up-regulation of MCP-1 expression caused by interferon gamma (IFN-gamma) was not sensitive to COX inhibitors. Quiescent HSC did not show detectable expression of COX-2, which became evident after activation in culture, and while TNF-alpha and IL-1alpha markedly increased the expression of COX-2, IFN-gamma did not have any effects. Pretreatment of HSC with the stable cyclic adenosine monophosphate (cAMP) analog, 8-bromo cAMP, reverted the effects of the COX-2 inhibitor, but not of a nuclear factor-kappaB (NF-kappaB) inhibitor, demonstrating that prostaglandins modulate MCP-1 expression via production of cAMP. On the other hand, the action of NF-kappaB inhibitors was negligible in IFN-gamma-stimulated cells. These findings indicate that cross-talk between cytokines and a prostaglandin-cAMP pathway differentially regulates the proinflammatory potential of HSC, contributing to the modulation of liver tissue inflammation.