Immaginazioni dell’aldilà nella narrativa italiana del secondo dopoguerra ad oggi

For centuries Christianity’s imaginary netherworld has been influencing literary works such as Dante’s Commedia. As time went by, this vision of the afterlife has gradually lost ground. The man of industrialised society does not care about life after death anymore. Hell seems to have moved upwards to our world, in mundane life. Thus, since after WW2, several Italian writers as different in style and worldview as Giorgio Manganelli, Ermanno Cavazzoni, Dino Buzzati, Guido Piovene, Raffaello Baldini, Daniele Benati and Federico Fellini, have created a modern vision of the afterlife where borders tend to blur and sometimes even vanish

A new method for avalanche hazard mapping using a combination of statistical and deterministic models

International audienceThe purpose of the present paper is to propose a new method for avalanche hazard mapping using a combination of statistical and deterministic modelling tools. The methodology is based on frequency-weighted impact pressure, and uses an avalanche dynamics model embedded within a statistical framework. The outlined procedure provides a useful way for avalanche experts to produce hazard maps for the typical case of avalanche sites where historical records are either poorly documented or even completely lacking, as well as to derive confidence limits on the proposed zoning. The methodology is implemented using avalanche information from Iceland and the Swiss mapping criteria, and applied to an Icelandic real world avalanche-mapping problem

Risk assessment in avalanche-prone areas

AbstractThis paper addresses the problem of defining a proper method for formal risk analysis in avalanche-prone areas. In this study, risk is defined as the annual probability of being killed by an avalanche for someone living or working permanently in a building under a hazardous hillside. A new methodology to estimate the hazard component of avalanche risk based on the use of dynamic models is introduced. This approach seems to have some advantages over the current methods based on statistical analysis of historic avalanche data. The vulnerability component of risk is formulated as a function of avalanche velocity, according to previous formulations. However, given the lack of knowledge on how avalanche impact damages structures and causes fatalities, the effect on the resulting risk mapping of using different vulnerability relations is explored. The potential of the proposed approach for evaluating the residual risk after the implementation of defensive structural work is discussed

Predictors of HER2 gene amplification in immunohistochemistry score 2+ Early Breast Cancer according to 2018 ASCO/CAP guidelines: a single institution analysis.

Background: HER2 overexpression occurs in approximately 15-20% of invasive breast cancers (BC). From a pathological point of view HER2 positivity is defined by intense circumferential membrane complete staining in more than 10% of tumour cells in immunohistochemistry (IHC score 3+). When complete circumferential staining is weak to moderate (IHC score 2+) double probe in situ ibridation (ISH) is mandatory to define HER2 status. In 2018 ASCO/CAP guidelines were updated to provide additional guidance in HER2 equivocal cases to allow a greater discrimination between positive and negative cases. Our aim is to find predictors of HER2 positivity among IHC score 2+ early breast cancer specimens analysed according to 2018 ASCO/CAP guidelines. Patients and methods: 253 cases of early BC diagnosed at Modena Cancer Center between November 2013 and August 2017 were identified. Stage, ISH result, hormonal receptor status (HR), proliferation index (MIB1), and histological grade were captured; menopausal status was available too. All IHC score 2+ cases were reclassified according to 2018 ASCO/CAP guidelines. The association between pathological tumour features, clinical characteristics and ISH positivity was assessed using Fisher test. Results: Overall, 25.7% IHC score 2+ BC resulted HER2 amplified in double probe ISH. High tumour grade (G3 vs G1-2) and MIB1 > 20% significantly predict HER2 ISH amplification (p=0,0001). No correlation was found according to HR, stage, or menopausal status. The majority (185; 98.4%) of HER2-ve BC were reclassified as group 5 (HER2/ CEP17 ratio <2 and HER2 copy number <4 signals/cell) except for 3 specimens classified as group 4 (HER2/CEP17 RATIO <2 and HER2 copy number \ub34 but <6 signals/cell). In HER2+ve group the majority (62; 95.3%) specimens were group 1 (HER2/CEP17 RATIO >2 and HER2 copy number =4 signals/cell), no specimen was group 2, and only 3 cases were classified as group 3 (HER2/CEP17 RATIO <2 and HER2 copy number >6 signals/cell). Conclusions: In this IHC score 2+ BC series, reclassification according to 2018 ASCO/CAP guidelines identified only 4.6% group 3 and 1.6% group 4 cases. The routinely assessment of grading and proliferation index could help to predict HER2 amplification in IHC score 2+ samples even if it must not substitute ISH assay in determining eligibility for HER2 targeted therapies

The utility of the 3D imaging software in the macroscopic rendering of complex gynecologic specimens

A new generation of three dimensional (3D) imaging software for the anatomical rendering of the human body, and related surgical pathologies, is postulated. Its practical application is underlined

Role of Intrinsic Subtype Analysis with PAM50 in Hormone Receptors Positive HER2 Negative Metastatic Breast Cancer: A Systematic Review.

Endocrine therapy (ET), associated with CDK 4/6 inhibitors, represents the first choice of treatment for HR+/HER2- metastatic breast cancer (mBC). Primary or secondary endocrine resistance could develop; however validated biomarkers capable of predicting such a conditions are not available. Several studies have shown that HR+/HER2- mBC comprises five intrinsic subtypes. The purpose of this systematic review was to analyze the potential correlations between intrinsic subtype, efficacy of treatment, and patient outcome. Five papers that analyzed the intrinsic subtype with PAM50 assay in patients (pts) with HR+/HER2- mBC treated with ET (alone or in combination) within seven phase III clinical trials (EGF30008, BOLERO-2, PALOMA-2,3, MONALEESA-2,3,7) were identified. Non-luminal subtypes are more frequent in endocrine-resistant pts and in metastatic sites (vs. primary tumors), have less benefit from ET, and worse prognosis. Among these, HER2-enriched subtypes are similar to HER2+ tumors and benefit from the addition of anti-HER2 agents (lapatinib) and, for less clear reasons, of ribociclib (unconfirmed data for palbociclib and everolimus). Basal-like subtypes are similar to triple-negative tumors, making them more sensitive to chemotherapy. The intrinsic subtype is also not static but can vary over time with the evolution of the disease. Currently, the intrinsic subtype does not play a decisive role in the choice of treatment in clinical practice, but has potential prognostic and predictive value that should be further investigated

Targeting PI3K/AKT/mTOR Pathway in Breast Cancer: From Biology to Clinical Challenges

Breast cancer (BC) is the most common women cancer and cause of cancer death. Despite decades of scientific progress in BC treatments, the clinical benefit of new drugs is modest in several cases. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway mutations are frequent in BC (20-40%) and are significant causes of aggressive tumor behavior, as well as treatment resistance. Improving knowledge of the PI3K/AKT/mTOR pathway is an urgent need. This review aims to highlight the central role of PI3K-mTORC1/C2 mutations in the different BC subtypes, in terms of clinical outcomes and treatment efficacy. The broad base of knowledge in tumor biology is a key point for personalized BC therapy in the precision medicine era

T-DM1 efficacy in trastuzumab-pertuzumab pre-treated HER2 positive metastatic breast cancer patients: a meta-analysis.

Background: Current guidelines consider T-DM1 the standard 2nd line therapy for HER2 positive metastatic breast cancer (MBC) patients following trastuzumab (T) + pertuzumab (P) and taxane 1st line treatment. Despite this, there are no prospective studies supporting this sequence. Methods: We performed a meta-analysis using real world data to determine the efficacy of T-DM1 after 1st line TP in HER2 positive MBC patients. We used a random-effect model to find differences in the rate of 1-year progression free survival (PFS) between TP pre-treated population and the EMILIA phase III pivotal trial. Results: Seven studies were eligible. The meta-analysis showed a combined 1-year PFS risk difference for T-DM1 efficacy after TP in 2nd or more lines of -0.122, with lower and upper limits of -0.253 and 0.010, respectively (p = 0.07), with low heterogeneity among studies (I2 0.01%, p = 0.836). Considering the four studies on T-DM1 in 2nd line setting, 1-year PFS risk was -0.034 (95% CI -0.207 - 0,139; p = 0.701) (I2 0.01%, p = 0.91). Conclusion: Overall, the efficacy of T-DM1 after TP seems to be similar to that previously reported in the EMILIA trial. In the second line setting, data are not mature enough to confirm T-DM1 efficacy in TP pre-treated population

Primary and secondary prevention to effectively reduce the risk of bisphosphonate-related osteonecrosis of the jaw in patients with bone metastases .

Background Bone is one of the most frequent sites of metastasis in patients with advanced cancer. Nearly all patients with myeloma, 65–75% of patients with prostate or breast cancer, and 30–40% of patients with lung cancer or other solid tumors, eventually develop bone metastases. Bisphosphonates (BP), particularly zoledronic acid and denosumab, were demonstrated to effectively reduce skeletal complications in patients with bone metastases. However, bisphosphonate-related osteonecrosis of the jaw (BRONJ) can occur spontaneously, favored by dental extraction, dental implant surgery, or denture wearing. The purpose of this study was to underline the role of dental prevention as an effective tool to reduce the risk of BRONJ. Material and methods BRONJ was identified with the standardized query “osteonecrosis” among all data from patients treated at Modena Cancer Center from 2005 to 2016. For each case, demographic and medical information were analyzed, as well as data about notification (year of occurrence, outcome), type and duration of BP exposure, and associated risk factors (dento-alveolar surgery, chemotherapy, antiangiogenics). Data were differently analyzed taking into account the implementation of a Dental Prevention Service in patients who are candidates for BP therapy.Results Among 1663 patients treated with BP, 63 cases of BRONJ were identified (3.8%). 44 female and 19 men with a median age of 69 years (range 47-90 years), have been treated with BP for bone metastases from breast cancer (54%), hematologic malignancy (21%), prostate cancer (13%), renal cancer (5%), lung cancer (2%) and other tumors (5%). 15 maxillae and 48 mandibles were involved. The trigger event was a dental extraction in 29% of the cases, being spontaneously the other 71%. The median time to BRONJ was 28 months (range 1-89.1 months) from the first dose of BP, and 25 was the mean number of BP doses administered before BRONJ. Overall, a preliminary odontoiatric evaluation was performed in only 14 cases (22%). All but one of these dentistry opinions were obtained after 2010 when the Dental Prevention Service was created, which is a drop out of the risk of BRONJ from 4.1 to 1.9%. Conclusions. Prevention of the BRONJ is critical in in bone metastatic patients. The incidence of BRONJ over time can drop to 1.9% when primary and secondary prevention measures are implemented in routine clinical practice

The design of avalanche protection dams : Recent practical and theoretical developments

This book discusses the design of dams and other protective measures in the run-out zones of wet- and dry-snow avalanches. It summarises recent theoretical developments and the results of field and laboratory studies, combining them with traditional design guidelines and principles to formulate design recommendations. Not discussed are hazard zoning, land use planning, evacuations, supporting structures in starting zones, snow fences in catchment areas, and other safety measures outside the run-out zone. Reinforcement of individual buildings also falls outside the scope of the book, as do protective measures against landslides and slushflows.European Comissio