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

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

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

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

Laryngeal neuroendocrine tumor with elevated serum calcitonin: a diagnostic and therapeutic challenge. Case report and review of literature

Introduction: Laryngeal neuroendocrine neoplasms (NENs) are a rare group of NENs of the neck, which commonly show immunostaining for calcitonin. Laryngeal NENs with calcitonin hypersecretion and lymph node metastases represent a diagnostic and therapeutic challenge, which should be included in the differential diagnosis of medullary thyroid carcinoma (MTC). We report a complex case of laryngeal NEN with calcitonin hypersecretion and a review of the literature. Case Presentation: A 59-year-old man presented with dysphagia, dyspnea, and lateral cervical mass; he was a smoker. At first imaging, a laryngeal lesion with lateral cervical lymphadenopathies was found, and it resulted as a moderately differentiated neuroendocrine tumor (G2), Ki67 = 5%, positive for calcitonin. Increased levels of serum calcitonin (50 pg/ml) were found. The patient started somatostatin analogs for lesions positivity to somatostatin receptor-based imaging. After 5 months, the disease progressed at 18F-fluorodeoxyglucose (18F-FDG) PET-CT, and also new painful cutaneous lesions occurred. Considering high serum levels of calcitonin, differential diagnosis with MTC was required. Patient performed a thyroid color Doppler ultrasound, nodule fine needle aspiration, calcitonin dosage in fine needle washout fluid, and a calcium gluconate stimulation test. After multidisciplinary evaluation, we decided to perform a total thyroidectomy associated with lateral cervical lymphadenectomy and resection of skin metastases. No MTC was found. Two of the five resected lymph nodes, left upper parathyroid, and skin lesions were metastases of NEN G2, positive for calcitonin. After 2 months, new painful skin lesions occurred, and a target therapy with everolimus 10 mg/day was started. After 6 months of therapy, partial metabolic response with a reduction of 53.7% of radiotracer uptake at primary tumor was detected together with an improvement of patient's quality of life. Conclusions: The present case is the seventh described in the literature of laryngeal NEN associated with elevated serum calcitonin levels and the first case with parathyroid metastasis, suggesting the importance of a correct differential diagnosis between MTC and calcitonin-secreting laryngeal NEN, using an integrated approach of biochemistry and advanced imaging. This is also the first time that somatostatin analogs and then everolimus were used in this setting, resulting in clinical and partial metabolic response

Temporal variation in cave bear (Ursus spelaeus) dentition: The stratigraphic sequence of Scladina Cave, Belgium

© 2018 Elsevier Ltd The supposed herbivorous cave bear (Ursus spelaeus) occupied Europe throughout the Quaternary. Being subject to large spatial variation has led to the intensive study on its geographical polymorphism, generating debates on sub-speciation. However, temporal morphological information on the species is somewhat lacking. Here, we apply geometric morphometrics (GMM) technique to investigate temporal morphological variation in molar size and shape of Ursus spelaeus from different chronostratigraphic sediment units in a geographically confined site (Scladina Cave, Belgium), covering approximately 100,000 years. Our findings show significant morphological variation between groups analysed in both size and shape. M2 shows a chronological size increase with PCA plots visually expressing differences in all groups, relating to a buccolingual expansion and an increase of the talon masticatory platform through time. Reduction in the M1 is also shown, possibly to maintain biomechanical performance of dentition for effective mastication, more so in groups relating to the latter stages of the Quaternary. Findings suggest a rapid response to climatic factors constraining consumable food sources, with GMM offering a promising analytical approach in understanding the palaeobiology, palaeoecology and morphological variation in extinct and extant fossil mammals

Health-related quality of life in patients with neuroendocrine neoplasms: a two-wave longitudinal study

Purpose: Scientific knowledge on health-related quality of life (HRQoL) in patients with neuroendocrine neoplasm (NEN) is still limited and longitudinal assessment of HRQoL over the time in NEN patients are scarce. The current study aimed to assess the role of clinical severity and heterogeneity of NEN, as well as resilience, in the HRQoL of NEN patients over the course of a year. Methods: 39 consecutive NEN patients (25 men and 14 women) aged from 29 to 73 years participated in a longitudinal Italian multicentric study. The main outcome measure concerned the severity and heterogeneity of NEN, HRQoL, and resilience. Results: Over the course of a year, higher levels of the global health (GH) were associated to the absence of distant metastases, while the presence of metastases with higher levels of fatigue, diarrhea, and financial difficulties. Higher levels of resilience are still associated with better GH and lower levels of fatigue, diarrhea, and financial difficulties, but no longer with constipation. Furthermore, patients with gastroenteropancreatic NEN still have higher scores on constipation, but not on GH, fatigue, diarrhea, and financial difficulties. Patients with hereditary NEN continue to have greater GH than those with a sporadic NEN and lower fatigue, diarrhea, and financial difficulties. Conclusion: These findings showed that the effects of severity and clinical heterogeneity of the NEN on HRQoL may change over time. This evidence should lead clinicians to monitor the HRQoL of NEN patients throughout the course of the disease and psychologists to implement evidence-based resilience interventions

Targeting epigenetic alterations in cancer stem cells

Oncogenes or tumor suppressor genes are rarely mutated in several pediatric tumors and some early stage adult cancers. This suggests that an aberrant epigenetic reprogramming may crucially affect the tumorigenesis of these tumors. Compelling evidence support the hypothesis that cancer stem cells (CSCs), a cell subpopulation within the tumor bulk characterized by selfrenewal capacity, metastatic potential and chemo-resistance, may derive from normal stem cells (NSCs) upon an epigenetic deregulation. Thus, a better understanding of the specific epigenetic alterations driving the transformation from NSCs into CSCs may help to identify efficacious treatments to target this aggressive subpopulation. Moreover, deepening the knowledge about these alterations may represent the framework to design novel therapeutic approaches also in the field of regenerative medicine in which bioengineering of NSCs has been evaluated. Here, we provide a broad overview about: 1) the role of aberrant epigenetic modifications contributing to CSC initiation, formation and maintenance, 2) the epigenetic inhibitors in clinical trial able to specifically target the CSC subpopulation, and 3) epigenetic drugs and stem cells used in regenerative medicine for cancer and diseases

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