A principle-based approach to AI: the case for European Union and Italy

As Artificial Intelligence (AI) becomes more and more pervasive in our everyday life, new questions arise about its ethical and social impacts. Such issues concern all stakeholders involved in or committed to the design, implementation, deployment, and use of the technology. The present document addresses these preoccupations by introducing and discussing a set of practical obligations and recommendations for the development of applications and systems based on AI techniques. With this work we hope to contribute to spreading awareness on the many social challenges posed by AI and encouraging the establishment of good practices throughout the relevant social areas. As points of novelty, the paper elaborates on an integrated view that combines both human rights and ethical concepts to reap the benefits of the two approaches. Moreover, it proposes innovative recommendations, such as those on redress and governance, which add further insight to the debate. Finally, it incorporates a specific focus on the Italian Constitution, thus offering an example of how core legislations of Member States might contribute to further specify and enrich the EU normative framework on AI

Risk of cancer in relatives of testicular cancer patients.

The incidence of cancer at sites other than the testis has been investigated in the families of 797 Norwegian and 178 Swedish patients diagnosed with testicular cancer during 1981-91. In the families of the Norwegian patients, the total number of cancers in the relatives was significantly lower than the expected number derived from national incidence rates [observed number of cancers 250, expected number of cancers 281.92, standardised incidence ratio (SIR) 0.89, 95% confidence interval (CI) 0.78-1.00]. This finding can be accounted for almost entirely by the finding of fewer than expected prostate and gastrointestinal cancers in the parents of cases. The other common cancers were found at slightly lower than or near the expected levels in the relatives. In the Swedish cohort, which accounts for less than 20% of cases, the observed number of cancers was very close to the expected number. Fourteen fathers of cases had prostate cancer compared with 27.57 prostate cancers expected, giving a SIR of 0.51 (P=0.006). Mothers had more lung cancers (ten cases observed, SIR=2.11, P=0.04) and cancers of the endometrium than expected (13 cases observed, SIR=1.73, P=0.09). These findings may be interpreted as support for theories proposing hormonal dysfunction as causing testicular cancer. Fifty-four gastrointestinal cancers were observed in the parents compared with 68.48 expected (SIR=0.78, P=0.082). Furthermore, testicular cancer was not found to be associated with the known dominantly inherited cancer syndromes [Familial breast (-ovarian) cancer, hereditary no-polyposis colon cancer]. However, one patient belonged to a Li-Fraumeni family, raising the possibility that testicular cancer may be an infrequent component of this rare cancer syndrome. This study supports the hypothesis that families of testicular cancer patients are not prone to cancer

Exhaustive CoMFA and CoMSIA analyses around different chemical entities: a ligand-based study exploring the affinity and selectivity profiles of 5-HT1A ligands

The 5-hydroxytryptamine (5-HT1A) receptors represent an attractive target in drug discovery. In particular, 5-HT1A agonists and partial agonists are deeply investigated for their potential role in the treatment of anxiety, depression, ischaemic brain disorder and more recently, of pain. On the other hand, 5-HT1A antagonists have been revealed promising compounds in cognition disorders and, lately, in cancer. Thus, the discovery of 5HT1A ligands is nowadays an appealing research activity in medicinal chemistry. In this work, Comparative Molecular Fields Analysis (CoMFA) and Comparative Molecular Similarity Index Analysis (CoMSIA) were applied on an in-house library of 5-HT1A ligands bearing different chemical scaffolds in order to elucidate their affinity and selectivity for the target. Following this procedure, a number of structural modifications have been drawn for the development of much more effective 5-HT1AR ligands

Familial testicular cancer in Norway and southern Sweden.

Information about occurrence of testicular cancer (TC) in relatives of TC patients has been collected using questionnaires from 797 out of 922 consecutive Norwegian and 178 out of 237 Swedish patients with TC seen at the Norwegian Radium Hospital and the University Hospital Lund in Sweden during 1981-91. Fifty-one Norwegian and five Swedish patients had a relative with confirmed TC. Thus, 51/922 (5.5%) of the Norwegian and 5/237 (2.1%) of the Swedish patients treated during the time interval investigated were considered to have familial TC. Thirty-two of the patients had an affected first-degree relative. Expected numbers of cancers in the relatives were computed from data in the Norwegian and Swedish Cancer Registries. Standardised incidence ratios (SIRs) were taken as observed numbers of TC/expected numbers of TC in the relatives. The SIR for brothers was 10.2 (95% confidence interval 6.22-15.77). SIR for fathers was 4.3 (1.6-9.3) and for sons 5.7 (0.7-23.2). The point estimate for the risk to brothers in the Norwegian part of the sample to develop TC by the age of 60 was 4.1% (95% CI 1.7-6.6%). This study indicates that genetic factors may be of greater importance in TC than previously assumed. Patients with familial testicular cancer had bilateral tumours more often than sporadic cases (9.8% bilaterality in familial vs 2.8% in sporadic cases, P=0.02). For patients with seminoma age of onset was lower in familial than in sporadic cases (32.9 vs 37.6 years, P=0.06). In father-son pairs, there was a statistically significant earlier age of diagnosis in the generation of sons (28.8 years vs 44.9 years, P=0.04). The prevalence of undescended testis (UDT) did not seem to be higher in familial than in sporadic TC (8.2% in familial TC and 13.3% in sporadic cases). This may indicate that different factors are of importance for the development of familial TC and UDT

Combining functional metagenomics and glycoanalytics to identify enzymes that facilitate structural characterization of sulfated N-glycans

Abstract Background Sulfate modification of N-glycans is important for several biological functions such as clearance of pituitary hormones or immunoregulation. Yet, the prevalence of this N-glycan modification and its functions remain largely unexplored. Characterization of N-glycans bearing sulfate modifications is hampered in part by a lack of enzymes that enable site-specific detection of N-glycan sulfation. In this study, we used functional metagenomic screening to identify enzymes that act upon sulfated N-acetylglucosamine (GlcNAc). Using multiplexed capillary gel electrophoresis with laser-induced fluorescence detection (xCGE-LIF) -based glycoanalysis we proved their ability to act upon GlcNAc-6-SO4 on N-glycans. Results Our screen identified a sugar-specific sulfatase that specifically removes sulfate from GlcNAc-6-SO4 when it is in a terminal position on an N-glycan. Additionally, in the absence of calcium, this sulfatase binds to the sulfated glycan but does not remove the sulfate group, suggesting it could be used for selective isolation of sulfated N-glycans. Further, we describe isolation of a sulfate-dependent hexosaminidase that removes intact GlcNAc-6-SO4 (but not asulfated GlcNAc) from a terminal position on N-glycans. Finally, the use of these enzymes to detect the presence of sulfated N-glycans by xCGE-LIF is demonstrated. Conclusion The present study demonstrates the feasibility of using functional metagenomic screening combined with glycoanalytics to discover enzymes that act upon chemical modifications of glycans. The discovered enzymes represent new specificities that can help resolve the presence of GlcNAc-6-SO4 in N-glycan structural analyses

Second cancer risk and mortality in men treated with radiotherapy for stage I seminoma

BACKGROUND: Patients with stage I testicular seminoma are typically diagnosed at a young age and treatment is associated with low relapse and mortality rates. The long-term risks of adjuvant radiotherapy in this patient group are therefore particularly relevant. METHODS: We identified patients and obtained treatment details from 12 cancer centres (11 United Kingdom, 1 Norway) and ascertained second cancers and mortality through national registries. Data from 2629 seminoma patients treated with radiotherapy between 1960 and 1992 were available, contributing 51,151 person-years of follow-up. RESULTS: Four hundred and sixty-eight second cancers (excluding non-melanoma skin cancers) were identified. The standardised incidence ratio (SIR) was 1.61 (95% confidence interval (CI): 1.47-1.76, P<0.0001). The SIR was 1.53 (95% CI: 1.39-1.68, P<0.0001) when the 32 second testicular cancers were also excluded. This increase was largely due to an excess risk to organs in the radiation field; for pelvic-abdominal sites the SIR was 1.62 (95% CI: 1.43-1.83), with no significant elevated risk of cancers in organs elsewhere. There was no overall increase in mortality with a standardised mortality ratio (SMR) of 1.06 (95% CI: 0.98-1.14), despite an increase in the cancer-specific mortality (excluding testicular cancer deaths) SMR of 1.46 (95% CI: 1.30-1.65, P<0.0001). CONCLUSION: The prognosis of stage I seminoma is excellent and it is important to avoid conferring long-term increased risk of iatrogenic disease such as radiation-associated second cancers

PO-0803: Validation of a pre-treatment delivery quality assurance method for the CyberKnife Synchrony System

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Three-times daily radiotherapy after chemotherapy in stage III non-small cell lung cancer. Single-institution prospective study

Aim: A prospective study for stage IIIA-B non-small cell lung cancer (NSCLC), with three-times daily (3td) radiotherapy (RT), after induction chemotherapy (iCT), with or without surgery. Patients and Methods: Induction cisplatin and gemcitabine chemotherapy was delivered. Surgery and postoperative (post-op) radiotherapy were planned for responsive stage IIIA patients; definitive irradiation was performed in unresectable III A and IIIB patients. Doses of 54.4 and 64.6 Gy were delivered for the post-op and definitive treatments, respectively. Results: Out of 52 patients (pts), 37 received 3tdRT as definitive (18 pts) or post-op treatment (19 pts). Overall, the failures were similar between post-op and definitive 3tdRT (78.9% vs. 77.8%). In the post-op treatment, metastases and local failures were 52.6% and 10.5%, respectively and in the definitive radiotherapy, the incidence was similar (local 33.3% vs. systemic 44.4%). The five-year overall survival (OS) was 25% for the post-op and 21% for the definitive patients (p=0.87). Conclusion: Three-times daily postoperative radiotherapy did not improve the outcome in NSCLC, but for unresectable patients, this approach may have a role in selected cases