Numerical and experimental analysis of the leaning Tower of Pisa under earthquake

Twenty years have passed from the most recent studies about the dynamic behavior of the leaning Tower of Pisa. Significant changes have occurred in the meantime, the most important ones concerning the soil-structure interaction. From 1999 to 2001, the foundation of the monument was consolidated through under-excavation, and the "Catino" at the basement was rigidly connected to the foundation. Moreover, in light of the recent advances in the field of earthquake engineering, past studies about the Tower must be revised. Therefore, the present research aims at providing new data and results about the structural response of the Tower under earthquake. As regards the experimental assessment of the Tower, the dynamic response of the structure recorded during some earthquakes has been analyzed in the time- and frequency-domain. An Array 2D test has been performed in the Square of Miracles to identify a soil profile suitable for site response analyses, thus allowing the definition of the free-field seismic inputs at the base of the Tower. On the other hand, a synthetic evaluation of the seismic input in terms of response spectra has been done by means of a hybrid approach that combines Probabilistic and Deterministic Seismic Hazard Assessment methods. Furthermore, natural accelerograms have been selected and scaled properly. A finite element model that takes into account the inclination of the structure has been elaborated, and it has been updated taking into account the available experimental results. Finally, current numerical and experimental efforts for enhancing the seismic characterization of the Tower have been illustrated

Leaning Tower of Pisa:recent advances on dynamic response and soil structure interaction

The Leaning Bell Tower of Pisa has been included in the list of the World Heritage Sites by UNESCO since 1987. Over the last 20 years, the Tower has successfully undergone a number of interventions to reduce its inclination. The Tower has also been equipped with a sensor network for seismic monitoring. In this study, preliminary results on the dynamic behavior of the monument are presented, including a review of historical seismicity in the region, identification of vibrational modes, definition of seismic input, site response analysis, and seismic response accounting for soil-structure interaction. This includes calibration of the dynamic impedances of the foundation to match the measured natural frequencies. The study highlights the importance of soil-structure interaction in the survival of the Tower during a number of strong seismic events since the middle ages

Seismic Reassessment of the Leaning Tower of Pisa:Monitoring, Site Response and SSI

The Tower of Pisa survived several strong earthquakes undamaged over the last 650 years, despite its leaning and limited strength and ductility. No credible explanation for its remarkable seismic performance exists to date. A reassessment of this unique case history in light of new seismological, geological, structural, and geotechnical information is reported, aiming to address this question. The following topics are discussed: (1) dynamic structural identification based on recorded earthquake data; (2) geophysical site characterization using a two-dimensional array; (3) seismic hazard and site response analysis considering horizontal and vertical motions; and (4) soil-structure interaction (SSI) analysis calibrated using lab and field data. A substantial shift in natural period, from about 0.35 s to over 1 s (a threefold increase, the largest known for a building of that height) caused by SSI, a wave parameter (1∕σ) of about 0.3, and a minor effect of vertical ground motion are identified and may explain the lack of earthquake damage on the Tower. Recommendations for future research, including the need to establish a seismic bedrock deeper than 500 m, are provided

Long-term and real-world safety and efficacy of retroviral gene therapy for adenosine deaminase deficiency

Adenosine deaminase (ADA) deficiency leads to severe combined immunodeficiency (SCID). Previous clinical trials showed that autologous CD34+ cell gene therapy (GT) following busulfan reduced-intensity conditioning is a promising therapeutic approach for ADA-SCID, but long-term data are warranted. Here we report an analysis on long-term safety and efficacy data of 43 patients with ADA-SCID who received retroviral ex vivo bone marrow-derived hematopoietic stem cell GT. Twenty-two individuals (median follow-up 15.4 years) were treated in the context of clinical development or named patient program. Nineteen patients were treated post-marketing authorization (median follow-up 3.2 years), and two additional patients received mobilized peripheral blood CD34+ cell GT. At data cutoff, all 43 patients were alive, with a median follow-up of 5.0 years (interquartile range 2.4-15.4) and 2 years intervention-free survival (no need for long-term enzyme replacement therapy or allogeneic hematopoietic stem cell transplantation) of 88% (95% confidence interval 78.7-98.4%). Most adverse events/reactions were related to disease background, busulfan conditioning or immune reconstitution; the safety profile of the real world experience was in line with premarketing cohort. One patient from the named patient program developed a T cell leukemia related to treatment 4.7 years after GT and is currently in remission. Long-term persistence of multilineage gene-corrected cells, metabolic detoxification, immune reconstitution and decreased infection rates were observed. Estimated mixed-effects models showed that higher dose of CD34+ cells infused and younger age at GT affected positively the plateau of CD3+ transduced cells, lymphocytes and CD4+ CD45RA+ naive T cells, whereas the cell dose positively influenced the final plateau of CD15+ transduced cells. These long-term data suggest that the risk-benefit of GT in ADA remains favorable and warrant for continuing long-term safety monitoring. Clinical trial registration: NCT00598481 , NCT034786

Minimally invasive vs. open segmental resection of the splenic flexure for cancer: a nationwide study of the Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CNN)

Background Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes. Methods This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016. The primary endpoint assessing efficacy was the overall survival (OS). The secondary endpoints included cancer-specific mortality (CSM), recurrence rate (RR), short-term clinical outcomes (a composite of Clavien-Dindo > 2 complications and 30-day mortality), and pathological outcomes (a composite of lymph nodes removed >= 12, and proximal and distal free resection margins length >= 5 cm). For these composites, a 6% noninferiority margin was chosen based on clinical relevance estimate. Results A total of 606 patients underwent either an open (208, 34.3%) or a MI (398, 65.7%) SFC segmental resection. At univariable analysis, OS and CSM were improved in the MI group (log-rank test p = 0.004 and Gray's tests p = 0.004, respectively), while recurrences were comparable (Gray's tests p = 0.434). Cox multivariable analysis did not support that OS and CSM were better in the MI group (p = 0.109 and p = 0.163, respectively). Successful pathological outcome, observed in 53.2% of open and 58.3% of MI resections, supported noninferiority (difference 5.1%; 1-sided 95%CI - 4.7% to infinity). Successful short-term clinical outcome was documented in 93.3% of Open and 93.0% of MI procedures, and supported noninferiority as well (difference - 0.3%; 1-sided 95%CI - 5.0% to infinity). Conclusions Among patients with SFC, the minimally invasive approach met the criterion for noninferiority for postoperative complications and pathological outcomes, and was found to provide results of OS, CSM, and RR comparable to those of open resection

BPSDiary study protocol: a multi-center randomized controlled trial to compare the efficacy of a BPSD diary vs. standard care in reducing caregiver's burden

Behavioral and Psychological Symptoms of Dementia (BPSD) are a heterogeneous set of psychological and behavioral abnormalities seen in persons with dementia (PwD), significantly impacting their quality of life and that of their caregivers. Current assessment tools, such as the Neuropsychiatric Inventory (NPI), are limited by recall bias and lack of direct observation. This study aims to overcome this limitation by making caregiver reports more objective through the use of a novel instrument, referred to as the BPSDiary. This randomized controlled trial will involve 300 caregiver-PwD dyads. The objective is to evaluate whether the use of the BPSDiary could significantly reduce caregiver burden, assessed using the Zarit Burden Interview (ZBI), compared to usual care. The study will include adult PwD, caregivers living with or close to the patient, and BPSD related to the HIDA (hyperactivity, impulsivity, irritability, disinhibition, aggression, agitation) domain. Caregivers randomized to the intervention arm will use the BPSDiary to record specific BPSD, including insomnia, agitation/anxiety, aggression, purposeless motor behavior, and delusions/hallucinations, registering time of onset, severity, and potential triggers. The primary outcome will be the change in ZBI scores at 3 months, with secondary outcomes including changes in NPI scores, olanzapine equivalents, NPI-distress scores related to specific BPSD domains, and caregiver and physician satisfaction. The study will be conducted in 9 Italian centers, representing diverse geographic and sociocultural contexts. While potential limitations include the relatively short observation period and the focus on specific BPSD disturbances, the BPSDiary could provide physicians with objective data to tailor appropriate non-pharmacological and pharmacological interventions. Additionally, it may empower caregivers by encouraging reflection on BPSD triggers, with the potential to improve the quality of life for both PwD and their caregivers.Trial registryNCT05977855