Managing rare and undetectable events in risk assessment: the case of a satellite system launch project

Assessing the wide diversity of risk types in large and complex projects using the traditional hyperbolic iso-risks curves may seem a simplistic and reductive approach, and evaluating the risk factor through the multiplication of likelihood and severity parameters results in defining as dangerous those risks that are associated either with rare but devastating consequences or with probable but minor effects. In this work, the authors aimed at focusing on those risks that, despite their low occurrence probability, may significantly compromise a project result. To this extent, a different formula has been used to compute the risk factor, keeping into account risk detectability and evaluating the potential consequences in four different domains (cost, time, performance, reputation). This approach has been validated on the case of a large industrial project related to the launch of an innovative mobile telecommunications system, collecting the experts' opinions in a primary Italian firm in aerospace industry

Olfactory evaluation in obstructive sleep apnoea patients

The sense of smell has a high impact on the quality of life. The aim of the present study was to investigate olfactory dysfunction in patients with obstructive sleep apnoea syndrome (OSAS) and correlate the severity of disease with olfactory dysfunction. The relationships between nasal obstruction, nasal mucociliary cleareance and olfactory tests were also evaluated. Sixty patients with a diagnosis of OSAS were enrolled and underwent olfactory function evaluation. In all patients olfactory performance was tested with the Sniffin’ Sticks method. Mucociliary transport times and anterior rhinomanometry were performed to identify eventual nasal obstruction and deficits in nasal mucociliary clearance. Olfactory dysfunction was present in 22 (36.6%) patients of the study group: of these, hyposmia was present in 19 (86.4%) and anosmia in 3 (13.6%). The mean TDI score in the study group was 30. A strong correlation between the olfactory dysfunction and severity of sleep apnoea measured using the AHI was found. Patients with OSA would seem to have a high incidence of olfactory dysfunction. The degree of olfactory dysfunction appears to be related to the severity of disease. However, other co-factors such as nasal obstruction and reduced mucociliary clearance might also play a role in of the aetiology of this condition

Instruções técnicas para o cultivo comercial de hortaliças em Rondônia.

Instrucoes tecnicas dirigidas a extensionistas, baseadas em trabalhos de pesquisa e unidades de observacoes, conduzidas no periodo de 1984/86, pela EMBRAPA-UEPAE Porto Velho, em varios locais do Estado. Apresentam-se meios de superar algumas limitacoes tecnicas e contribui com o crescimento da atividade olericola e Rondonia. Inclui informacoes sobre propagacao, epoca de plantio e regioes aptas para o cultivo, preparo do solo, calagem, adubacao e adubacao organica, doencas e pragas, nematoides e rotacao de culturas.bitstream/item/55039/1/Circ.Tec.110001.pd

Obstructive sleep apnoea in patients treated for head and neck cancer: A systematic review of the literature

Background and objectives: Obstructive sleep apnoea (OSA) is clinically defined by signs of daytime sleepiness and objective measures of disordered breathing during sleep. The literature is still controversial on the incidence and aetiology of OSA secondary to head and neck cancer treatment. The aim of this systematic review is to evaluate and discuss the prevalence of OSA in patients treated with surgery and/or chemo/radiotherapy for head and neck cancer. Materials and methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search was performed on May 2020 using the MEDLINE database, Scopus, and Google Scholar. The searches were conducted using combinations of the following terms: head and neck cancer, OSA, radiotherapy, chemotherapy, partial laryngectomy, laryngeal cancer, neoplasm, tumour, carcinoma, and oropharyngeal cancer. Results: Our results suggest that head and neck cancer patients have a higher incidence of OSA (59.78%) compared to the general population; differences may occur based on the type of treatment. Conclusions: Clinicians should recognise the higher prevalence of OSA in patients treated for head and neck cancer and should consider a comprehensive sleep history as part of the evaluation and management of these patients. Further research is needed to evaluate the exact prevalence, aetiology, and correct management of OSA after treatment for head and neck cancer

20S proteasome mediated degradation of DHFR: implications in neurodegenerative disorders

The 20S proteasome is responsible for the degradation of protein substrates implicated in the onset and progression of neurodegenerative disorders, such as a-synuclein and tau protein. Here we show that the 20S proteasome isolated from bovine brain directly hydrolyzes, in vitro, the dihydrofolate reductase (DHFR), demonstrated to be involved in the pathogenesis of neurodegenerative diseases. Furthermore, the DHFR susceptibility to proteolysis is enhanced by oxidative conditions induced by peroxynitrite, mimicking the oxidative environment typical of these disorders. The results obtained suggest that the folate metabolism may be impaired by an increased degradation of DHFR, mediated by the 20S proteasome

Immunotherapy in the Treatment of Metastatic Melanoma: Current Knowledge and Future Directions

Melanoma is one of the most immunologic malignancies based on its higher prevalence in immune-compromised patients, the evidence of brisk lymphocytic infiltrates in both primary tumors and metastases, the documented recognition of melanoma antigens by tumor-infiltrating T lymphocytes and, most important, evidence that melanoma responds to immunotherapy. The use of immunotherapy in the treatment of metastatic melanoma is a relatively late discovery for this malignancy. Recent studies have shown a significantly higher success rate with combination of immunotherapy and chemotherapy, radiotherapy, or targeted molecular therapy. Immunotherapy is associated to a panel of dysimmune toxicities called immune-related adverse events that can affect one or more organs and may limit its use. Future directions in the treatment of metastatic melanoma include immunotherapy with anti-PD1 antibodies or targeted therapy with BRAF and MEK inhibitors

Effect of polyphenolic compounds on the proteolytic activities of constitutive and immuno-proteasomes

The effect of several polyphenols on the 20S proteasomes, both the constitutive and the LMP proteasomes, isolated from bovine tissues, has been investigated. Polyphenolic compounds show many biological activities such as antiviral, antibacterial, antifungal, anti-inflammatory, antimutagenic, and antiallergic activities. However, the molecular mechanism underlying these effects has not been identified. It is well established that polyphenols possess inhibitory activities on several enzymes and among them the 20S proteasome. In the present work, the ChT-L, BrAAP, PGPH, and T-L activities of the isolated constitutive and immuno-proteasomes were assayed in order to get an overall information on the polyphenols binding to the complexes. The effects of the polyphenols on the proteasomal activities were analyzed, taking into account the different subunits composition of the two complexes. Furthermore the same activities were measured on whole extracts from cancer cells exposed to EGCG and gallic acid, evaluating, also, their antioxidant action under oxidative stress. EGCG and gallic acid are able to affect the 20S proteasomes functionality, depending on the complex subunit composition and, in cell extracts, they behave both as antioxidants and proteasome effectors

50 Hz Extremely Low Frequency Electromagnetic Fields Enhance Protein Carbonyl Groups Content in Cancer Cells: Effects on Proteasomal Systems

Electromagnetic fields are an assessed cause of prolonging free radicals lifespan. This study was carried out to investigate the influence of extremely low frequency electromagnetic fields on protein oxidation and on the 20S proteasome functionality, the complex responsible for the degradation of oxidized proteins. Caco 2 cells were exposed, for 24–72 hours, to 1 mT, 50 Hz electromagnetic fields. The treatment induced a time-dependent increase both in cell growth and in protein oxidation, more evident in the presence of TPA, while no changes in cell viability were detected. Exposing the cells to 50 Hz electromagnetic fields caused a global activation of the 20S proteasome catalytic components, particularly evident at 72 hours exposure and in the presence of TPA. The finding that EGCG, a natural antioxidant compound, counteracted the field-related pro-oxidant effects demonstrates that the increased proteasome activity was due to an enhancement in intracellular free radicals

Bcl-2 protein: a prognostic factor inversely correlated to p53 in non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) prognosis is strictly related to well-established clinicopathological parameters which have unfortunately become insufficient in the prognostic evaluation of this type of cancer. As p53 and bcl-2 gene deregulations are frequently involved in several types of epithelial malignancies, we investigated the Bcl-2 and p53 protein expression in 91 and 101 cases of NSCLC respectively. The expression was then compared with established indicators of prognosis and biological behaviour of the tumours. No relationship was observed between Bcl-2 and either clinicopathological or biological parameters such as histology, grading, tumour status, nodal metastasis and proliferative activity evaluated by scoring proliferating cell nuclear antigen expression and Ki-67 immunoreactivity. However, the mean Bcl-2 expression was significantly lower in patients who developed metastasis during follow-up or died of metastatic disease (P = 0.006 and P = 0.01 respectively). Moreover, survival probability was higher in patients who expressed the Bcl-2 protein (P = 0.0002). In contrast with this, p53 protein accumulation was observed in tumours with metastatic nodal involvement (P = 0.02) or in patients who developed metastasis during follow-up (P = 0.01), although no correlation was found between p53 expression and overall survival. An inverse relationship was also found between Bcl-2 and the anti-oncogene protein product p53 (P = 0.01). Thus, a high proportion of NSCLCs express p53 and Bcl-2 proteins and their expression may have prognostic importance

Tumour necrosis factor- α and transforming growth factor- β are significantly associated with better prognosis in non-small cell lung carcinoma: putative relation with BCL -2-mediated neovascularization

Recent in vivo and in vitro studies have demonstrated a wide spectrum of biologic activities of cytokines in the pathogenesis and progression of malignancy. Tumour necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β) have emerged as two of the many host-derived mediators that seem to interfere with both antiproliferative and tumorigenic effects in malignant tumours including lung cancer. However, their association with tumour prognosis or prognostic factors has not yet been completely clarified. In this study, we assessed TNF-α and TGF-β mRNA expression by RT-PCR technique in 61 NSCLC samples, demonstrating the presence of TNF-α and TGF-β mRNA in 55.74% and 45.9% of cases, respectively. We also evaluated the expression of the two distinct transmembrane TNF receptors. TNFR-I and TNFR-II, with a PCR-positive signal in 70.49% and 65.57% of cases, respectively. In 49 of the 61 cases, we evaluated the prognostic impact of the two growth-inhibiting factors using the Kaplan–Meier analysis. In the univariate analysis patients without nodal metastatic involvement (P = 0.02), less advanced tumour stage (P = 0.02) or TNF-α and TGF-β positive cancers (P = 0.01 and P = 0.03) showed a favourable prognosis in terms of overall survival. Since our previous studies demonstrated a significant association between NSCLC behaviour, neoangiogenesis and bcl -2 expression, we investigated the putative relation between TNF-α and TGF-β on the one hand, and vascular count (as a measure of tumour angiogenesis) and bcl -2 protein expression, on the other hand. Our results showed a significant direct association between TNF-α and bcl -2 (P = 0.05) and an inverse association between TNF-α and microvessel count (P = 0.03). Moreover, as previously demonstrated, we observed a significant inverse correlation between bcl -2 protein expression and vascular count (P = 0.05), suggesting that the favourable effect of TNF-α on clinical outcome may be related to a bcl -2-mediated low neovascular development. © 2000 Cancer Research Campaig