Therapeutic sequences in patients with grade 1−2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group

Purpose: Many different treatments are suggested by guidelines to treat grade 1−2 (G1−G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1−G2 NET. Methods: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation. Results: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1–G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03). Conclusions: SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1−G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy

Cloud resource orchestration in the multi-cloud landscape: a systematic review of existing frameworks

The number of both service providers operating in the cloud market and customers consuming cloud-based services is constantly increasing, proving that the cloud computing paradigm has successfully delivered its potential. Nevertheless, the unceasing growth of the cloud market is posing hard challenges on its participants. On the provider side, the capability of orchestrating resources in order to maximise profits without failing customers’ expectations is a matter of concern. On the customer side, the efficient resource selection from a plethora of similar services advertised by a multitude of providers is an open question. In such a multi-cloud landscape, several research initiatives advocate the employment of software frameworks (namely, cloud resource orchestration frameworks - CROFs) capable of orchestrating the heterogeneous resources offered by a multitude of cloud providers in a way that best suits the customer’s need. The objective of this paper is to provide the reader with a systematic review and comparison of the most relevant CROFs found in the literature, as well as to highlight the multi-cloud computing open issues that need to be addressed by the research community in the near future

DigiArt: towards a virtualization of Cultural Heritage

DigiArt is a Europe-wide project aimed at providing a new, cost efficient solution to the capture, processing and display of cultural artefacts. The project will change the ways in which the public interact with cultural objects and spaces in a dramatic way. This project is unique in its collaborative approach: cultural heritage professionals working directly with electrical, mechanical, optical and software engineers to develop a solution to current issues faced by the museum sector. The innovations created by the engineers are driven by the demand of the cultural heritage sector. The diversity of the objects and spaces of the three test museums are challenging the engineers to provide a tool useful for a broad variety of indoor and outdoor museums in the future. This goes from using Unmanned Aerial Vehicle (UAVs or drones) to fly and record large sites, to using scanners to record fine jewellery. As a case study, we present here the use-case of Scladina Cave. At the end of the project, the Scladina Cave Archaeological Centre will offer two different visitor experiences. The first uses virtual reality, which will be available anytime, anywhere, to anyone with an internet connected device. The second will use augmented reality technologies within the cave site. The augmented reality visit of the cave will enhance the tour of Scladina by offering visits that would not be possible where it not for the augmented reality, where 3D objects and animations will contribute to offer a new 3D-immersive experience

Optimal Placement of Micro-services Chains in a Fog Infrastructure

Fog computing emerged as a novel approach to deliver micro-services that support innovative applications. This paradigm is consistent with the modern approach to application development, that leverages the composition of small micro-services that can be combined to create value-added applications. These applications typically require the access from distributed data sources, such as sensors located in multiple geographic locations or mobile users. In such scenarios, the traditional cloud approach is not suitable because latency constraints may not be compatible with having time-critical computations occurring on a far away data-center; furthermore, the amount of data to exchange may cause high costs imposed by the cloud pricing model. A layer of fog nodes close to application consumers can host pre-processing and data aggregation tasks that can reduce the response time of latency-sensitive elaboration as well as the traffic to the cloud data-centers. However, the problem of smartly placing micro-services over fog nodes that can fulfill Service Level Agreements is far more complex than in the more controlled scenario of cloud computing, due to the heterogeneity of fog infrastructures in terms of performance of both the computing nodes and inter-node connectivity. In this paper, we tackle such problem proposing a mathematical model for the performance of complex applications deployed on a fog infrastructure. We adapt the proposed model to be used in a genetic algorithm to achieve optimized deployment decisions about the placement of micro-services chains. Our experiments prove the viability of our proposal with respect to meeting the SLA requirements in a wide set of operating conditions

Spatio-temporal analysis of the urban–rural gradient structure: an application in a Mediterranean mountainous landscape (Serra San Bruno, Italy)

Abstract. The most recent and significant transformations of European landscapes have occurred as a consequence of a series of diffused, varied and often connected phenomena: urban growth and sprawl, agricultural intensification in the most suitable areas and agricultural abandonment in marginal areas. These phenomena can affect dramatically ecosystems' structure and functioning, since certain modifications cause landscape fragmentation while others tend to increase homogeneity. Thus, a thorough comprehension of the evolution trends of landscapes, in particular those linked to urban-rural relations, is crucial for a sustainable landscape planning. In this framework, the main objectives of the present paper are: (a) to investigate Land Use/Land Cover (LULC) transformations and dynamics that occurred over the period 1955–2006 in the municipality of Serra San Bruno (Calabria, Italy), an area particularly representative of the Mediterranean mountainous landscape; (b) to compare the settlement growth with the urban planning tools in charge in the study area; (c) to examine the relationship between urban–rural gradient, landscape metrics, demographic and physical variables; (d) to investigate the evolution of urban–rural gradient composition and configuration along significant axes of landscape changes. Data with a high level of detail (minimum mapping unit 0.2 ha) were obtained through the digitisation of historical aerial photographs and digital orthophotos identifying LULC classes according to the Corine Land Cover legend. The investigated period was divided into four significant time intervals, which were specifically analysed to detect LULC changes. Differently from previous studies, in the present research the spatio-temporal analysis of urban–rural gradient was performed through three subsequent steps: (1) kernel density analysis of settlements; (2) analysis of landscape structure by means of metrics calculated using a moving window method; (3) analysis of composition and configuration of the urban–rural gradient within three landscape profiles located along significant axes of LULC change. The use of thematic overlays and transition matrices enabled a precise identification of the LULC changes that had taken place over the examined period. As a result, a detailed description and mapping of the landscape dynamics were obtained. Furthermore, landscape profiling technique, using continuous data, allowed an innovative and valuable approach for analysing and interpreting urban–rural gradient structure over space and time

The Middle Palaeolithic from Belgium: Chronostratigraphy, territorial management and culture on a mosaic of contrasting environments

peer reviewedThe Lower and Middle Palaeolithic in Belgium are represented in 442 find-sites dispersed across a small territory with contrasting geographical and geological characteristics. The close proximity of caves and open-air sites, as well as the variable access to good sources of flint between regions are of special interest. The dataset is composed primarily of lithic assemblages, rich palaeontological and archaeozoological documentation as well as Neandertal remains from 8 cave sites. This large amount of data facilitates the development of a chronostratigraphic framework from the very beginning of the Middle Palaeolithic (onset of MIS 8) to the end (within the MIS 3, around 36 ka uncal BP). This archaeological documentation also reveals that lithic production variability is multifactorial and includes site function, cultural perspectives, and mobility patterns related to the exploitation of natural resources in contrasting environments

Vitamin D deficiency and tumor aggressiveness in gastroenteropancreatic neuroendocrine tumors

Purpose: Data regarding vitamin D status in patients affected by gastroenteropancreatic (GEP) neuroendocrine tumor (NET) are limited and often showing contrasting results. The aim of the study was to evaluate the incidence of vitamin D deficiency (<20 ng/mL) in GEP-NET patients and compare the 25-hydroxyvitamin D (25(OH)D) levels with clinicopathological parameters and clinical outcome. Methods: A retrospective cross-sectional study including 75 low grade (G1-G2) GEP-NETs and 123 healthy controls matched for age, sex, and body mass index, was performed. Results: GEP-NET patients had significantly lower 25(OH)D levels compared to controls (17.9 ± 7.8 vs 24.2 ± 7.7 ng/mL, p < 0.0001). Ileal NETs were associated to lower 25(OH)D levels compared to other primary tumor sites (p = 0.049) and small bowel resection posed a significant increased risk of severe vitamin D deficiency (OR = 2.81, 95% CI = 1.25–3.37, p = 0.018). No correlation with somatostatin analogs treatment was found. 25(OH)D levels were significantly lower in G2 compared to G1 GEP-NETs (15.6 ± 7.8 vs 19.9 ± 7.4 ng/mL, p = 0.016) and in patients with progressive disease (12.6 ± 5.7 ng/mL) compared to those with stable disease (mean 21.5 ± 8.2 ng/mL, p = 0.001) or tumor free after surgery (19.6 ± 7.3 ng/mL, p = 0.002). Patients with vitamin D deficiency and insufficiency had shorter progression-free survival compared to those with sufficiency (p = 0.014), whereas no correlation was found with disease-specific survival. Conclusions: Vitamin D deficiency is highly prevalent among GEP-NETs and could be associated with high tumor grade and disease progression. Therefore, the monitoring of 25(OH)D levels is relevant in these patients and vitamin D supplementation should be considered in the management of GEP-NET patients with vitamin D deficiency or insufficiency

Spatio-temporal analysis of the urban–rural gradient structure: an application in a Mediterranean mountainous landscape (Serra San Bruno, Italy)

The most recent and significant transformations of European landscapes have occurred as a consequence of a series of diffused, varied and often connected phenomena: urban growth and sprawl, agricultural intensification in the most suitable areas and agricultural abandonment in marginal areas. These phenomena can affect dramatically ecosystems' structure and functioning, since certain modifications cause landscape fragmentation while others tend to increase homogeneity. Thus, a thorough comprehension of the evolution trends of landscapes, in particular those linked to urban-rural relations, is crucial for a sustainable landscape planning. In this framework, the main objectives of the present paper are: (a) to investigate Land Use/Land Cover (LULC) transformations and dynamics that occurred over the period 1955–2006 in the municipality of Serra San Bruno (Calabria, Italy), an area particularly representative of the Mediterranean mountainous landscape; (b) to compare the settlement growth with the urban planning tools in charge in the study area; (c) to examine the relationship between urban–rural gradient, landscape metrics, demographic and physical variables; (d) to investigate the evolution of urban–rural gradient composition and configuration along significant axes of landscape changes. Data with a high level of detail (minimum mapping unit 0.2 ha) were obtained through the digitisation of historical aerial photographs and digital orthophotos identifying LULC classes according to the Corine Land Cover legend. The investigated period was divided into four significant time intervals, which were specifically analysed to detect LULC changes. Differently from previous studies, in the present research the spatio-temporal analysis of urban–rural gradient was performed through three subsequent steps: (1) kernel density analysis of settlements; (2) analysis of landscape structure by means of metrics calculated using a moving window method; (3) analysis of composition and configuration of the urban–rural gradient within three landscape profiles located along significant axes of LULC change. The use of thematic overlays and transition matrices enabled a precise identification of the LULC changes that had taken place over the examined period. As a result, a detailed description and mapping of the landscape dynamics were obtained. Furthermore, landscape profiling technique, using continuous data, allowed an innovative and valuable approach for analysing and interpreting urban–rural gradient structure over space and time