Sviluppo e convalida di un metodo hplc per la determinazione di proclorperazina base e cleaning validation

Nel presente lavoro di tesi è stato sviluppato e convalidato un metodo analitico, mediante cromatografia liquida ad alte prestazioni (HPLC), per valutare il recupero di proclorperazina maleato da superfici, tramite campionamento con swab, dopo le attività di pulizia delle attrezzature dedicate alle produzioni farmaceutiche. La validazione della procedura si è basata sulla normativa ICH Q2(R1)che definisce le procedure e i criteri d’accettazione per la qualità dei prodotti farmaceutici e i metodi atti alla determinazione delle impurezze. L’attività di tesi si è svolta all’interno del laboratorio Life Science Services di SGS Sertec, in cui si applicano le norme di buona produzione (Good Manufacturing Practices, GMP) e le connesse rigidità per l'organizzazione del lavoro

Modello di stima dei costi sanitari e della capacity delle terapie intensive in Italia nel trattamento di pazienti affetti da COVID-19: valutazione dell’impatto di remdesivir

Introduction: Coronavirus disease 2019 (COVID-19) is caused by a severe acute respiratory syndrome coronavirus 2, which is a human coronavirus responsible for a pandemic. Direct interventions, i.e. physical distancing and use of protective devices, can prevent or limit contagions, however, it is also required to evaluate the optimization of limited resources, such as the Intensive Care Unit (ICU). For this purpose, it is relevant to estimate the impact of therapeutic solutions that reduce the probability that the patient transits to ICU in symptomatic subjects and in need of hospitalization. The therapeutic solutions allow a more rapid recovery of the patient and save scarce resources that can be used in the treatment of other patients. Methods: A forecasting model is designed to estimate the impact of one therapeutic solution, i.e. the antiretroviral Remdesivir, on both the capacity of intensive care and the healthcare costs for hospitals when managing the current emergency. A base case is presented as well as a best and a worst case scenario deriving from the sensitivity analyses. Results: The introduction of Remdesivir in patients receiving low-flow oxygen therapy with the purpose of reducing ICU accesses and deaths leads to 431 million euros cost savings and avoids 17,150 hospitalizations in intensive care and 6,923 deaths. In the best case, 294 million euros savings are estimated, whilst in the worst case the model estimates a saving of 512 million euros. Conclusions: Remdesivir has the potential to reduce the negative effects of the Coronavirus disease, improving patient conditions and reducing death tolls, and can also save scarce healthcare resources during this pandemic, resulting in a shorter hospital stay and fewer ICU admissions

Model for estimating the impact of healthcare costs in non-hospitalized Covid-19 patients treated with remdesivir

Objectives: In March 2020, the COVID-19 pandemic outbreak caused significant negative changes worldwide. Important investments were suddenly needed in the economic, social, and healthcare fields. This analysis sets out to show the economic impact of the administration of remdesivir in ambulatory patients, who are affected by Covid-19, at high risk for severe progression, and eligible for the antiviral treatment. Methods: The budget impact analysis is based on the assumptions already presented in a study published in 2020 by the same Authors. The analysis was updated with a new simulation of the pandemic curve which included the vaccination plan. Data were collected from official Italian sources and from the academic literature. The Italian National Health Service (NHS) perspective was used in the analysis. Remdesivir treatment was compared in terms of economic costs with the Standard of Care over a period of 20 weeks. Such timeframe was chosen because of the uncertainty of the pandemic evolution and considering that this is the time of a complete pandemic curve. A comparison with other therapeutic solutions was not performed in this analysis as the relative costs were not available at the time of the study. Results: The model estimates that, in 20 weeks, 8,002,015 subjects are infected by Covid-19, with a 0.8% hospitalization rate. Among hospitalized patients, 19.6% could be eligible for remdesivir treatment, for a total number of 3,619 patients, with a 12% market share. Conclusion: The analysis shows that remdesivir therapy is dominant and its use could determine a reduction in hospitalizations and transfers to intensive care units compared to the Standard of Care, with a potential saving of € 50.8 million and a decrease of the number of Covid-19-related deaths between 600 and 1,100

Pro-Atherogenic and Pro-Oxidant Diets Influence Semen and Blood Traits of Rabbit Bucks

: Many dietary factors can affect sperm traits. We compared the effect of diets rich in pro-oxidant (flaxseed oil) and pro-atherogenic (coconut oil) substances without added antioxidants on semen traits, using the rabbit as an animal model. Thirty rabbit bucks (8 months old) were fed three diets for 150 days: CNT (control) a standard diet; HA (high-atherogenic) standard diet + 3% coconut oil, and HO (high-oxidizing) standard diet + 3% flaxseed oil. Semen samples were collected weekly for the evaluation of qualitative traits (kinetics, viability) and the oxidative damage (MDA and cytokines). Blood was collected at the start (T0) and end (T8) of the experimental period for the assessment of the oxidative damage (MDA and isoprostanoids), lipid profile, and testosterone. A worsening of sperm kinetics and viability was recorded in the HA group. Lipid oxidation in seminal plasma, as well as isoprostanoids in blood (F3-IsoPs and F4-NeuroPs), increased in both the HO and HA groups. A high level of TNF-α, a marker of inflammatory status, was recorded in the seminal plasma of the HA group. The resulting outcomes were mainly attributable to the different fatty acid profiles (SFA vs. PUFA) of the diets, which modulated an inflammatory/oxidative response

Integrated hybrid Raman/fiber Bragg grating interrogation scheme for distributed temperature and point dynamic strain measurements

We propose and experimentally demonstrate the feasibility of an integrated hybrid optical fiber sensing interrogation technique that efficiently combines distributed Raman-based temperature sensing with fiber Bragg grating (FBG)-based dynamic strain measurements. The proposed sensing system is highly integrated, making use of a common optical source/receiver block and exploiting the advantages of both (distributed and point) sensing technologies simultaneously. A multimode fiber is used for distributed temperature sensing, and a pair of FBGs in each discrete sensing point, partially overlapped in the spectral domain, allows for temperature-independent discrete strain measurements. Experimental results report a dynamic strain resolution of 7.8  nε/√Hz within a full range of 1700 με and a distributed temperature resolution of 1°C at 20 km distance with 2.7 m spatial resolution

The most luminous blue quasars at 3.0<z<3.3. II. CIV/X-ray emission and accretion disc physics

We analyse the properties of the CIV broad emission line in connection with the X-ray emission of 30 bright SDSS quasars at z~3.0-3.3 with pointed XMM-Newton observations, which were selected to test the suitability of AGN as cosmological tools. In our previous work, we found that a large fraction (~25%) of the quasars in this sample are X-ray underluminous by factors of >3-10. As absorbing columns of >10$^{23}$ cm$^{-2}$ can be safely ruled out, their weakness is most likely intrinsic. Here we explore possible correlations between the UV and X-ray features of these sources to investigate the origin of X-ray weakness. We fit their UV SDSS spectra and analyse their CIV properties (e.g., equivalent width, EW; line peak velocity, $\upsilon_{\rm peak}$) as a function of the X-ray photon index and 2-10 keV flux. We confirm the trends of CIV $\upsilon_{\rm peak}$ and EW with UV luminosity at 2500 angstrom for both X-ray weak and X-ray normal quasars, as well as the correlation between X-ray weakness and CIV EW. In contrast to some recent work, we do not observe any clear relation between the 2-10 keV luminosity and $\upsilon_{\rm peak}$. We find a correlation between the hard X-ray flux and the integrated CIV flux for X-ray normal quasars, whilst X-ray weak quasars deviate from the main trend by more than 0.5 dex. We argue that X-ray weakness might be interpreted in a starved X-ray corona picture associated with an ongoing disc-wind phase. If the wind is ejected in the vicinity of the black hole, the extreme-UV radiation that reaches the corona will be depleted, depriving the corona of seeds photons and generating an X-ray weak quasar. Yet, at the largest UV luminosities (>10$^{47}$ erg s$^{-1}$), there will still be an ample reservoir of ionising photons that can explain the excess CIV emission observed in the X-ray weak quasars with respect to normal sources of similar X-ray luminosities.Comment: 22 pages, 15 figures (with 3 more figures in the Appendix), abstract abridged. Accepted for publication in A&

X-ray properties and obscured fraction of AGN in the J1030 Chandra field

The 500ks Chandra ACIS-I observation of the field around the $z=6.31$ quasar SDSS J1030+0524 is currently the 5th deepest extragalactic X-ray survey. The rich multi-band coverage of the field allowed for an effective identification and redshift determination of the X-ray source counterparts: to date a catalog of 243 extragalactic X-ray sources with either a spectroscopic or photometric redshift estimate in the range $z\approx0-6$ is available over a 355 arcmin$^2$ area. Given its depth and the multi-band information, this catalog is an excellent resource to investigate X-ray spectral properties of distant Active Galactic Nuclei (AGN) and derive the redshift evolution of their obscuration. We performed a thorough X-ray spectral analysis for each object in the sample, measuring its nuclear column density $N_{\rm H}$ and intrinsic (de-absorbed) 2-10 keV rest-frame luminosity, $L_{2-10}$. Whenever possible, we also used the presence of the Fe K$_\alpha$ emission line to improve the photometric redshift estimates. We measured the fractions of AGN hidden by column densities in excess of $10^{22}$ and $10^{23}$cm$^{-2}$ ($f_{22}$ and $f_{23}$, respectively) as a function of $L_{2-10}$ and redshift, and corrected for selection effects to recover the intrinsic obscured fractions. At $z\sim 1.2$, we found $f_{22}\sim0.7-0.8$ and $f_{23}\sim0.5-0.6$, respectively, in broad agreement with the results from other X-ray surveys. No significant variations with X-ray luminosity were found within the limited luminosity range probed by our sample (log$L_{2-10}\sim 42.8-44.3$). When focusing on luminous AGN with log$L_{2-10}\sim44$ to maximize the sample completeness up to large cosmological distances, we did not observe any significant change in $f_{22}$ or $f_{23}$ over the redshift range $z\sim0.8-3$. Nonetheless, the obscured fractions we measure are significantly higher than ...Comment: A&A, in pres

LBT-MODS spectroscopy of high-redshift candidates in the Chandra J1030 field. A newly discovered z∼\sim2.8 large scale structure

We present the results of a spectroscopic campaign with the Multi-Object Double Spectrograph (MODS) instrument mounted on the Large Binocular Telescope (LBT), aimed at obtaining a spectroscopic redshift for seven Chandra J1030 sources with a photometric redshift >=2.7 and optical magnitude r_AB=[24.5-26.5]. We obtained a spectroscopic redshift for five out of seven targets: all of them have z_spec>=2.5, thus probing the reliability of the Chandra J1030 photometric redshifts. The spectroscopic campaign led to the serendipitous discovery of a z~2.78 large scale structure (LSS) in the J1030 field: the structure contains four X-ray sources (three of which were targeted in the LBT-MODS campaign) and two non-X-ray detected galaxies for which a VLT-MUSE spectrum was already available. The X-ray members of the LSS are hosted in galaxies that are significantly more massive (log(M_*/M_sun)=[10.0-11.1]) than those hosting the two MUSE-detected sources (log(M_*/M_sun)<10). Both observations and simulations show that massive galaxies, and particularly objects having log(M_*/M_sun)>10, are among the best tracers of large scale structures and filaments in the cosmic web. Consequently, our result can explain why X-ray-detected AGN have also been shown to be efficient tracers of large scale structures.Comment: 16 pages, 9 Figures. Accepted for publication in Astronomy and Astrophysic

Raman-based distributed temperature sensor with 1 m spatial resolution over 26 km SMF using low-repetition-rate cyclic pulse coding

We experimentally investigate the benefits of a new optical pulse coding technique for long-range, meter and submeter scale Raman-based distributed temperature sensing on standard single-mode optical fibers. The proposed scheme combines a low-repetition-rate quasi-periodic pulse coding technique with the use of standard high-power fiber lasers operating at 1550 nm , allowing for what we believe is the first long-range distributed temperature measurement over single-mode fibers (SMFs). We have achieved 1 m spatial resolution over 26 km of SMF, attaining 3°C temperature resolution within 30 s measurement time

Intra-and extra-hospitalization monitoring of vital signs. Two sides of the same coin. Perspectives from Lims and Greenline study operators

Background: In recent years, due to the epidemiological transition, the burden of very complex patients in hospital wards has increased. Telemedicine usage appears to be a potential high-impact factor in helping with patient management, allowing hospital personnel to assess conditions in out-of-hospital scenarios. Methods: To investigate the management of chronic patients during both hospitalization for disease and discharge, randomized studies (LIMS and Greenline-HT) are ongoing in the Internal Medicine Unit at ASL Roma 6 Castelli Hospital. The study endpoints are clinical outcomes (from a patient’s perspective). In this perspective paper, the main findings of these studies, from the operators’ point of view, are reported. Operator opinions were collected from structured and unstructured surveys conducted among the staff involved, and their main themes are reported in a narrative manner. Results: Telemonitoring appears to be linked to a reduction in side-events and side-effects, which represent some of most commons risk factors for re-hospitalization and for delayed discharge during hospitalization. The main perceived advantages are increased patient safety and the quick response in case of emergency. The main disadvantages are believed to be related to low patient compliance and an infrastructural lack of optimization. Conclusions: The evidence of wireless monitoring studies, combined with the analysis of activity data, suggests the need for a model of patient management that envisages an increase in the territory of structures capable of offering patients subacute care (the possibility of antibiotic treatments, blood transfusions, infusion support, and pain therapy) for the timely management of chronic patients in the terminal phase, for which treatment in acute wards must be guaranteed only for a limited time for the management of the acute phase of their diseases