An Unsupervised Spectrogram Cross-Correlation Method to Assess ELM Triggering Efficiency by Pellets

The high confinement mode (H-mode) is considered the optimal regime for the production of energy through nuclear fusion for industrial purposes since it allows to increase the energy confinement time of the plasma roughly by a factor of two. Consequently, it has been selected at the moment as the standard scenario for the next generation of devices, such as ITER. However, pressure-driven edge instabilities, known as edge localized modes (ELMs), are a distinct feature of this plasma regime. Their extrapolated thermal and particle peak loads on the plasma-facing components (PFC) of the next generation of devices are expected to be so high as to damage such structures, compromising the normal operations of the reactors themselves. Consequently, the induced loads have to be controlled; this can be achieved by mitigating ELMs. A possibility then lays in increasing the ELMs frequency to lower the loads on the PFCs. As already demonstrated at JET, the pellet pacing of ELMs is considered one of the most promising techniques for such scope, and its optimization is therefore of great interest for present and future operations of nuclear fusion facilities. In this work, we suggest a method to access primary pieces of information to perform statistics, assess and characterize the pacing efficiency. The method, tested on JET data, is based on the clustering (k-means) of convoluted signals, using so-called spectrogram cross-correlation, between the measured pellets and ELMs time traces. Results have also been obtained by taking advantage of a new type of diagnostic for measuring the ELMs dynamic, based on synthetic diamond sensors, faster than the standard spectroscopic cameras used at JET

Extremely large and hot multilayer Keplerian disk around the O-type protostar W51N: The precursors of the HCHII regions?

We present sensitive high angular resolution (0.57$''$-0.78$''$) SO, SO$_2$, CO, C$_2$H$_5$OH, HC$_3$N, and HCOCH$_2$OH line observations at millimeter and submillimeter wavelengths of the young O-type protostar W51 North made with the Submillimeter Array (SMA). We report the presence of a large (of about 8000 AU) and hot molecular circumstellar disk around this object, which connects the inner dusty disk with the molecular ring or toroid reported recently, and confirms the existence of a single bipolar outflow emanating from this object. The molecular emission from the large disk is observed in layers with the transitions characterized by high excitation temperatures in their lower energy states (up to 1512 K) being concentrated closer to the central massive protostar. The molecular emission from those transitions with low or moderate excitation temperatures are found in the outermost parts of the disk and exhibits an inner cavity with an angular size of around 0.7$''$. We modeled all lines with a Local Thermodynamic Equilibrium (LTE) synthetic spectra. A detail study of the kinematics of the molecular gas together with a LTE model of a circumstellar disk shows that the innermost parts of the disk are also Keplerian plus a contracting velocity. The emission of the HCOCH$_2$OH reveals the possible presence of a warm ``companion'' located to the northeast of the disk, however its nature is unclear. The emission of the SO and SO$_2$ is observed in the circumstellar disk as well as in the outflow. We suggest that the massive protostar W51 North appears to be in a phase before the presence of a Hypercompact or an Ultracompact HII (HC/UCHII) region, and propose a possible sequence on the formation of the massive stars.Comment: Accepted to Ap

Molecules in G1.6-0.025 - 'Hot' Chemistry in the Absence of Star Formation at the Periphery of the Galactic Center Region

We present molecular line mapping of the Giant Molecular Cloud G1.6-0.025, which is located at the high longitude end of the Central Molecular Zone of our Galaxy. We assess the degree of star formation activity in that region using several tracers and find very little. We made a large scale, medium (2') resolution map in the J = 2-1 transition of SiO for which we find clumpy emission over a ~0.8 x 0.3 degree-sized region stretching along the Galactic plane. Toward selected positions we also took spectra in the easy to excite J_k=2_k-1_k quartet of CH3OH and the CS 2-1 line. Throughout the cloud these \meth lines are, remarkably, several times stronger than, both, the CS and the SiO lines. The large widths of all the observed lines, similar to values generally found in the Galactic center, indicate a high degree of turbulence. Several high LSR velocity clumps that have 0-80 km/s higher velocities than the bulk of the molecular cloud appear at the same projected position as "normal" velocity material; this may indicate cloud-cloud collisions. Statistical equilibrium modeling of the CH3OH lines observed by us and others yield relatively high densities and moderate temperatures for a representative dual velocity position. We find 8 10^4 cm-3/30 K for material in the G1.6-0.025 cloud and a higher temperature (190 K), but a 50% lower density in a high velocity clump projected on the same location. Several scenarios are discussed in which shock chemistry might enhance the CH3OH and SiO abundances in G1.6-0.025 and elsewhere in the Central Molecular Zone.Comment: 51 pages incl. 9 figures and 6 Tables, ApJ (in press

Efficacy of ketamine in refractory convulsive status epilepticus in children: A protocol for a sequential design, multicentre, randomised, controlled, open-label, non-profit trial (KETASER01)

Introduction: Status epilepticus (SE) is a lifethreatening neurological emergency. SE lasting longer than 120 min and not responding to first-line and second-line antiepileptic drugs is defined as 'refractory' (RCSE) and requires intensive care unit treatment. There is currently neither evidence nor consensus to guide either the optimal choice of therapy or treatment goals for RCSE, which is generally treated with coma induction using conventional anaesthetics (high dose midazolam, thiopental and/or propofol). Increasing evidence indicates that ketamine (KE), a strong N-methyl-D-aspartate glutamate receptor antagonist, may be effective in treating RCSE. We hypothesised that intravenous KE is more efficacious and safer than conventional anaesthetics in treating RCSE. Methods and analysis: A multicentre, randomised, controlled, open-label, non-profit, sequentially designed study will be conducted to assess the efficacy of KE compared with conventional anaesthetics in the treatment of RCSE in children. 10 Italian centres/ hospitals are involved in enrolling 57 patients aged 1 month to 18 years with RCSE. Primary outcome is the resolution of SE up to 24 hours after withdrawal of therapy and is updated for each patient treated according to the sequential method. Ethics and dissemination: The study received ethical approval from the Tuscan Paediatric Ethics Committee (12/2015). The results of this study will be published in peer-reviewed journals and presented at international conferences

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription

The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Effect of wood smoke exposure on vascular function and thrombus formation in healthy fire fighters

Background: Myocardial infarction is the leading cause of death in fire fighters and has been linked with exposure to air pollution and fire suppression duties. We therefore investigated the effects of wood smoke exposure on vascular vasomotor and fibrinolytic function, and thrombus formation in healthy fire fighters. Methods: In a double-blind randomized cross-over study, 16 healthy male fire fighters were exposed to wood smoke (~1 mg/m3 particulate matter concentration) or filtered air for one hour during intermittent exercise. Arterial pressure and stiffness were measured before and immediately after exposure, and forearm blood flow was measured during intra-brachial infusion of endothelium-dependent and -independent vasodilators 4–6 hours after exposure. Thrombus formation was assessed using the ex vivo Badimon chamber at 2 hours, and platelet activation was measured using flow cytometry for up to 24 hours after the exposure. Results: Compared to filtered air, exposure to wood smoke increased blood carboxyhaemoglobin concentrations (1.3% versus 0.8%; P &lt; 0.001), but had no effect on arterial pressure, augmentation index or pulse wave velocity (P &gt; 0.05 for all). Whilst there was a dose-dependent increase in forearm blood flow with each vasodilator (P &lt; 0.01 for all), there were no differences in blood flow responses to acetylcholine, sodium nitroprusside or verapamil between exposures (P &gt; 0.05 for all). Following exposure to wood smoke, vasodilatation to bradykinin increased (P = 0.003), but there was no effect on bradykinin-induced tissue-plasminogen activator release, thrombus area or markers of platelet activation (P &gt; 0.05 for all). Conclusions: Wood smoke exposure does not impair vascular vasomotor or fibrinolytic function, or increase thrombus formation in fire fighters. Acute cardiovascular events following fire suppression may be precipitated by exposure to other air pollutants or through other mechanisms, such as strenuous physical exertion and dehydration.Originally included in thesis in manuscript form.</p