Attack-Surface Metrics, OSSTMM and Common Criteria Based Approach to “Composable Security” in Complex Systems

In recent studies on Complex Systems and Systems-of-Systems theory, a huge effort has been put to cope with behavioral problems, i.e. the possibility of controlling a desired overall or end-to-end behavior by acting on the individual elements that constitute the system itself. This problem is particularly important in the “SMART” environments, where the huge number of devices, their significant computational capabilities as well as their tight interconnection produce a complex architecture for which it is difficult to predict (and control) a desired behavior; furthermore, if the scenario is allowed to dynamically evolve through the modification of both topology and subsystems composition, then the control problem becomes a real challenge. In this perspective, the purpose of this paper is to cope with a specific class of control problems in complex systems, the “composability of security functionalities”, recently introduced by the European Funded research through the pSHIELD and nSHIELD projects (ARTEMIS-JU programme). In a nutshell, the objective of this research is to define a control framework that, given a target security level for a specific application scenario, is able to i) discover the system elements, ii) quantify the security level of each element as well as its contribution to the security of the overall system, and iii) compute the control action to be applied on such elements to reach the security target. The main innovations proposed by the authors are: i) the definition of a comprehensive methodology to quantify the security of a generic system independently from the technology and the environment and ii) the integration of the derived metrics into a closed-loop scheme that allows real-time control of the system. The solution described in this work moves from the proof-of-concepts performed in the early phase of the pSHIELD research and enrich es it through an innovative metric with a sound foundation, able to potentially cope with any kind of pplication scenarios (railways, automotive, manufacturing, ...)

The new TNM classification of lymph node metastasis minimises stage migration problems in gastric cancer patients

The present study aimed at investigating whether in gastric cancer patients stage migration occurs with extension of lymphadenectomy, when node metastases are staged according to the new pN classification (UICC 1997). The investigation involved 921 patients, who underwent R0 gastric resection for gastric cancer between 1988 and 1998 in three different Italian centres: Verona (n=236), Forlì (n=409), Siena (n=276). The relation among lymphadenectomy and pN category was assessed by Kendall's partial rank-order correlation coefficient, controlling for depth of tumour invasion. A direct evaluation of the Will Rogers phenomenon was accomplished in the Verona series, by comparing the number of positive nodes actually observed with the number of positive nodes which would have been retrieved by a less extended lymphadenectomy (D1). The number of positive nodes increased remarkably with the enlargement of lymphadenectomy, especially in pT2 patients (from 2.2±3.9 in D1 to 3.9±5.0 in D3) and in pT3/pT4 patients (from 5.1±5.9 in D1 to 11.3±12.6 in D3). Non-parametric statistics highlighted a weak (Kendall's partial T=0.128) but significant (P<0.001) correlation between pN category and extension of lymphadenectomy. In the direct analysis of the Verona series, 22 patients out of 230 (9.6%) migrated to a lower pN tier when ignoring positive nodes retrieved from the second and third level. This percentage increased to 39.1% (90 out of 230) when adopting the TNM 87 classification. In conclusion stage migration is of minor importance in gastric cancer patients, staged according to the new pN classification

Control architecture to provide E2E security in interconnected systems: the (new) SHIELD approach

Modern Systems are usually obtained as incremental composition of proper (smaller and SMART) subsystems interacting through communication interfaces. Such flexible architecture allows the pervasive provisioning of a wide class of services, ranging from multimedia contents delivery, through monitoring data collection, to command and control functionalities. All these services requires that the adequate level of robustness and security is assured at End-to- End (E2E) level, according to user requirements that may vary depending on the specific context or the involved technologies. A flexible methodology to dynamically control the security level of the service being offered is then needed. In this perspective, the authors propose an innovative control architecture able to assure E2E security potentially in any application, by dynamically adapting to the underlying systems and using its resources to “build the security”. In particular, the main novelties of this solution are: i) the possibility of dynamically discovering and composing the available functionalities offered by the environment to satisfy the security needs and ii) the possibility of modelling and measuring the security through innovative technology-independent metrics. The results presented in this paper moves from the solutions identified in the pSHIELD project and enrich them with the innovative advances achieved through the nSHIELD research, still ongoing. Both projects have been funded by ARTEMIS-JU

Conversion gastrectomy for stage IV unresectable gastric cancer: a GIRCG retrospective cohort study

Background: The aim of this study is to report the experience with conversion surgery from six Gruppo Italiano Ricerca Cancro Gastrico (GIRCG) centers, focusing our analysis on factors affecting survival and the risk of recurrence. Methods: A retrospective, multicenter cohort study was performed in patients who had undergone conversion gastrectomy between 2005 and 2017. Data were extracted from a GIRCG database including all metastatic gastric cancer patients submitted to surgery. Only stage IV unresectable tumors/metastases which became resectable after chemotherapy were included in this analysis. Results: Forty-five resected M1 patients were included in the analysis. Reasons for being deemed unresectable at diagnosis were peritoneal involvement (PCI &gt; 6) (n = 38, 84.4%), distant metastatic nodes (n = 3, 6.6%) and extensive liver involvement (n = 4, 8.8%). Median follow-up was 25&nbsp;months (IQR 9-50). Median overall survival from surgery was 15&nbsp;months and 1-, 3- and 5-year survivals were 57.2, 36.1 and 24%, respectively. Median progression-free survival was 12&nbsp;months with 1- and 3-year survival of 46.4 and 33.9%, respectively. At cox regression analysis the only independent prognostic factor for OS was the presence of more than one type of metastasis (HR 4.41, 95% CI 1.72\u201311.3, p = 0.002). A positive microscopic resection margin was the only risk factor for recurrence (HR 5.72, 95% CI 1.04\u201331.4, p = 0.045). Conclusions: Unresectable stage IV GC patients could benefit from radical surgery after chemotherapy and achieve long survivals. The main prognostic factor for these patients was the presence of more than one type of extra-gastric metastatic involvement

Genetic and epigenetic alterations of cdh1 regulatory regions in hereditary and sporadic gastric cancer

E-cadherin is a key player in gastric cancer (GC) and germline alterations of CDH1, its encoding gene, are responsible for Hereditary Diffuse Gastric Cancer (HDGC) syndrome. This study aimed at elucidating the role of genetic variants and DNA methylation of CDH1 promoter and enhancers in the regulation of gene expression. For this purpose, we analyzed genetic variants of the CDH1 gene through Next-Generation Sequencing (NGS) in a series of GC cell lines (NCI-N87, KATO-III, SNU-1, SNU-5, GK2, AKG, KKP) and the corresponding CDH1 expression levels. By bisulfite genomic sequencing, we analyzed the methylation status of CDH1 regulatory regions in 8 GC cell lines, in a series of 13 sporadic GC tissues and in a group of 20 HDGC CDH1-negative patients and 6 healthy controls. The NGS analysis on CDH1 coding and regulatory regions detected genetic alterations in 3 out of 5 GC cell lines lacking functional E-cadherin. CDH1 regulatory regions showed different methylation patterns in patients and controls, GC cell lines and GC tissues, expressing different E-cadherin levels. Our results showed that alterations in terms of genetic variants and DNA methylation patterns of both promoter and enhancers are associated with CDH1 expression levels and have a role in its regulation.This research and its authors were funded by IRCCS IRST (G.T., C.M., R.D. V.A., M.R., F.R., M.C., S.P., G.M., D.C., P.U.) and by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020–Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT–Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) (C.S.J., R.B.-M., A.A., C.O.). This work was also financed by the project NORTE-01-0145-FEDER-000029 (CANCER)-supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF)–project POCI-01-0145-FEDER-016390 (CancelStem) and PTDC/BTM-TEC/30164/2017 (3DChroMe), funded by ERDF, POCI and FCT

Neuroanatomy and cadaver dissection in Italy: History, medicolegal issues, and neurosurgical perspectives.

Despite the significant Italian tradition of important anatomical studies, an outdated law historically influenced by the Catholic church restricts the use of cadavers for teaching and scientific purposes. The object of the present paper was to trace the historical evolution of the Italian anatomical tradition, particularly neuroanatomical studies, in relation to the juridical regulations on the use of cadavers today. Special attention was paid to the opportunities offered to neurosurgery by using cadavers and to the scientific and social issues in neurosurgical training in the twenty-first century. Considering the new Common European Constitution, the authors advocate a political solution from the European community to improve the quality of training in the disciplines with a social impact such as neurosurgery

Development and Multicenter Validation of a Novel Immune-Inflammation-Based Nomogram to Predict Survival in Western Resectable Gastric and Gastroesophageal Junction Adenocarcinoma (GEA): The NOMOGAST

Background. More than 50% of operable GEA relapse after curative-intent resection. We aimed at externally validating a nomogram to enable a more accurate estimate of individualized risk in resected GEA. Methods. Medical records of a training cohort (TC) and a validation cohort (VC) of patients undergoing radical surgery for c/uT2-T4 and/or node-positive GEA were retrieved, and potentially interesting variables were collected. Cox proportional hazards in univariate and multivariate regressions were used to assess the effects of the prognostic factors on OS. A graphical nomogram was constructed using R software’s package Regression Modeling Strategies (ver. 5.0-1). The performance of the prognostic model was evaluated and validated. Results. The TC and VC consisted of 185 and 151 patients. ECOG:PS &gt; 0 (p &lt; 0.001), angioinvasion (p &lt; 0.001), log (Neutrophil/Lymphocyte ratio) (p &lt; 0.001), and nodal status (p = 0.016) were independent prognostic values in the TC. They were used for the construction of a nomogram estimating 3- and 5-year OS. The discriminatory ability of the model was evaluated with the c-Harrell index. A 3-tier scoring system was developed through a linear predictor grouped by 25 and 75 percentiles, strengthening the model’s good discrimination (p &lt; 0.001). A calibration plot demonstrated a concordance between the predicted and actual survival in the TC and VC. A decision curve analysis was plotted that depicted the nomogram’s clinical utility. Conclusions. We externally validated a prognostic nomogram to predict OS in a joint independent cohort of resectable GEA; the NOMOGAST could represent a valuable tool in assisting decision-making. This tool incorporates readily available and inexpensive patient and disease characteristics as well as immune-inflammatory determinants. It is accurate, generalizable, and clinically effectivex

Detection of sentinel and non-sentinel lymph node micrometastases by complete serial sectioning and immunohistochemical analysis for gastric cancer

<p>Abstract</p> <p>Background</p> <p>We investigated the presence and distribution of the sentinel and the non-sentinel node micrometastases using complete serial sectioning and immunohistochemical staining (IHC), to inspect whether lymph node micrometastases spread to the sentinel lymph nodes first.</p> <p>Methods</p> <p>A total of 35 patients, who underwent gastrectomy with a sentinel lymph node biopsy for gastric cancer, were enrolled in this study. Total of 1028 lymph nodes of 35 patients having gastric cancer without metastasis of lymph node by permanent section with hematoxylin and eosin staining (H&E) were selected. There were 252 sentinel nodes and the other 776 were non-sentinel nodes. All nodes were sectioned serially and stained alternately with H&E and IHC. Lymph node micrometastases was defined as proving to be positive first either the IHC or the complete serial sectioning.</p> <p>Results</p> <p>Micrometastases were detected in 4 (11%) of the 35 patients, 6 (0.58%) of 1028 nodes. Of these 4 patients, 3 had micrometastases exclusively in sentinel nodes, and the other had micrometastasis in both sentinel and non-sentinel nodes. There was no patient who had the micrometasitases only in non-sentinel nodes.</p> <p>Conclusion</p> <p>These results support the concept that lymph node micrometastasis of gastric cancer spreads first to sentinel nodes.</p

Clinical outcomes of patients with complicated post-operative course after gastrectomy for cancer: a GIRCG study using the GASTRODATA registry

Gastrectomy for gastric cancer is still performed in Western countries with high morbidity and mortality. Post-operative complications are frequent, and effective diagnosis and treatment of complications is crucial to lower the mortality rates. In 2015, a project was launched by the EGCA with the aim of building an agreement on list and definitions of post-operative complications specific for gastrectomy. In 2018, the platform www.gastrodata.org was launched for collecting cases by utilizing this new complication list. In the present paper, the Italian Research Group for Gastric Cancer endorsed a collection of complicated cases in the period 2015–2019, with the aim of investigating the clinical pictures, diagnostic modalities, and treatment approaches, as well as outcome measures of patients experiencing almost one post-operative complication. Fifteen centers across Italy provided 386 cases with a total of 538 complications (mean 1.4 complication/patient). The most frequent complications were non-surgical infections (gastrointestinal, pulmonary, and urinary) and anastomotic leaks, accounting for 29.2% and 17.3% of complicated patients, with a median Clavien–Dindo score of II and IIIB, respectively. Overall mortality of this series was 12.4%, while mortality of patients with anastomotic leak was 25.4%. The clinical presentation with systemic septic signs, the timing of diagnosis, and the hospital volume were the most relevant factors influencing outcome