Risk analysis and reliability of the GERDA Experiment extraction and ventilation plant at Gran Sasso mountain underground laboratory of Italian National Institute for Nuclear Physics

The aim of this study is the risk analysis evaluation about argon release from the GERDA experiment in the Gran Sasso underground National Laboratories (LNGS) of the Italian National Institute for Nuclear Physics (INFN). The GERDA apparatus, located in Hall A of the LNGS, is a facility with germanium detectors located in a wide tank filled with about 70 m3 of cold liquefied argon. This cryo-tank sits in another water-filled tank (700 m3) at atmospheric pressure. In such cryogenic processes, the main cause of an accidental scenario is lacking insulation of the cryo-tank. A preliminary HazOp analysis has been carried out on the whole system. The risk assessment identified two possible top-events: explosion due to a Rapid Phase Transition - RPT and argon runaway evaporation. Risk analysis highlighted a higher probability of occurrence of the latter top event. To avoid emission in Hall A, the HazOp, Fault Tree and Event tree analyses of the cryogenic gas extraction and ventilation plant have been made. The failures related to the ventilation system are the main cause responsible for the occurrence. To improve the system reliability some corrective actions were proposed: the use of UPS and the upgrade of damper opening devices. Furthermore, the Human Reliability Analysis identified some operating and management improvements: action procedure optimization, alert warnings and staff training. The proposed model integrates the existing analysis techniques by applying the results to an atypical work environment and there are useful suggestions for improving the system reliability

Somatic NGS Analysis of DNA Damage Response (DDR) Genes ATM, MRE11A, RAD50, NBN, and ATR in Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemo-Radiotherapy

Background: Neoadjuvant chemo-radiotherapy (nCRT) represents the standard of care for locally advanced rectal cancer (LARC); however, there exists no biomarker that can predict the cancer’s response to treatment as less than 20% of patients experience pathological complete response (pCR). Ionizing radiations induce double strand breaks (DSBs) and trigger a DNA damage response (DDR) involving ATM, ATR, and the MRN complex (MRE11, Rad50, and NBS1). In this study, we performed an extensive mutational analysis of the genes involved in the DDR pathway in LARC patients who have undergone nCRT. Methods: 13 LARC patients with pCR and 11 LARC patients with partial response (pPR) were investigated using a NGS dedicated panel, designed for formalin-fixed paraffin-embedded (FFPE) samples, containing ATR, ATM, and MRE11-RAD50-NBN genes. The identified variants were classified according to guidelines’ recommendations. Results: Eight non-benign variants, six of which were observed in 3 (23%) out of 13 pCR patients, were identified. In particular, a pCR patient carried out a pathogenetic frameshift mutation in exon 21 of the RAD50 gene. The two remaining non-benign missense variants were found in 2 (18%) out of 11 patients in the pPR group. Conclusions: Our data show that the genes involved in the Homologous Recombination (HR) pathway are rarely mutated in LARC; however, given the identification of a missense mutation in RAD 50 in one case of pCR, it could be worth exploring its potential role as a biomarker in larger series

Risk analysis and reliability of the GERDA Experiment extraction and ventilation plant at Gran Sasso mountain underground laboratory of Italian National Institute for Nuclear Physics

Abstract The aim of this study is the risk analysis evaluation about argon release from the GERDA experiment in the Gran Sasso underground National Laboratories (LNGS) of the Italian National Institute for Nuclear Physics (INFN). The GERDA apparatus, located in Hall A of the LNGS, is a facility with germanium detectors located in a wide tank filled with about 70 m3 of cold liquefied argon. This cryo-tank sits in another water-filled tank (700 m3) at atmospheric pressure. In such cryogenic processes, the main cause of an accidental scenario is lacking insulation of the cryo-tank. A preliminary HazOp analysis has been carried out on the whole system. The risk assessment identified two possible top-events: explosion due to a Rapid Phase Transition - RPT and argon runaway evaporation. Risk analysis highlighted a higher probability of occurrence of the latter top event. To avoid emission in Hall A, the HazOp, Fault Tree and Event tree analyses of the cryogenic gas extraction and ventilation plant have been made. The failures related to the ventilation system are the main cause responsible for the occurrence. To improve the system reliability some corrective actions were proposed: the use of UPS and the upgrade of damper opening devices. Furthermore, the Human Reliability Analysis identified some operating and management improvements: action procedure optimization, alert warnings and staff training. The proposed model integrates the existing analysis techniques by applying the results to an atypical work environment and there are useful suggestions for improving the system reliability

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

Pain assessment and management in Italian Haemophilia Centres

Although the widespread use of factor VIII/IX replacement therapy has significantly reduced the severity of arthropathy in persons with haemophilia (PWH), some develop degenerative joint changes, associated with significant pain. The aim of this survey was to investigate the management and perception of pain among Italian physicians who treat PWH