Radiation damage of FBK Silicon Photomultipliers for HEP applications

Silicon Photomultipliers (SiPMs) are photo-detectors currently experiencing a significant development in several fields: from medical applications to LiDAR, homeland security, analytical instrumentation, High Energy Physics (HEP). In particular, this work deals with SiPMs in HEP with a focus on their tolerance to the radiation. In fact, in HEP sensors are usually exposed to a large amount of radiation and they are expected to survive in such an environment. After a detailed introduction on the main SiPM characteristics, the main mechanisms of damage in SiPMs are addressed. They mainly consist into the generation of defects into the bulk, resulting in an increase of the noise, and in the surface layer, resulting in the generation of fixed charge in the oxide and defects at interface between the oxide and the silicon and, as a consequence, in an increase of the leakage current. This work aims to verify these theoretical assumptions through three irradiation test campaigns, where FBK SiPMs are exposed to the effects of both ionizing and non-ionizing radiation at medium-high doses. The first irradiation test took place at the Laboratori Nazionali del Sud (LNS) in 2019, where SiPMs were exposed to increasing 62 MeV proton fluences up to about 10^14 n_eq/cm^2. The main SiPMs parameters were assessed after irradiation and some information about the damage into the bulk of the sensors were derived. In fact, the noise was observed to increase significantly with respect to the non-irradiated SiPM, as expected from theory. Information were then extracted about activation energy, and a preferred spatial localization of the defects inside the single microcell was also observed. During the second irradiation test, FBK SiPMs were irradiated at the Trento Protontherapy Center with 74 MeV protons at increasing fluences, up to 6.4x10^11 n_eq/cm^2, using a custom setup which allowed direct reverse current-voltage measurement shortly after each irradiation step, reducing the impact of the annealing on the results. SiPMs were characterized extracting DCR, breakdown voltage and other key parameters from reverse current measurements. Then, the several technologies under test were compared using figures of merit such as Signal-to-Noise Ratio (SNR) and energy resolution, in X-rays or gamma-rays spectroscopy, assumed as possible applications. The NUV-HD technologies with smaller cell sizes showed the best best performances, in terms of energy resolution, SNR and noise level after annealing. The third irradiation campaign aimed to test the tolerance of FBK SiPMs to ionizing radiation through an X-rays irradiation at the TIFPA facility in Trento up to a dose of 100 kGy. SiPMs were irradiated using the same custom setup used in the second irradiation test, performing reverse current measurement after each irradiation step. After a 30-day annealing, samples irradiated at 100 kGy were fully characterized and compared to the non-irradiated ones. RGB-HD was the only technology to show a decrease of the PDE due to border effects in the electric field inside the microcells of the SiPM, while the NUV-HD-cryo was the only technology not showing variations neither in the noise nor in the PDE

The interplay among psychopathology, personal resources, context-related factors and real-life functioning in schizophrenia: stability in relationships after 4 years and differences in network structure between recovered and non-recovered patients

Improving real-life functioning is the main goal of the most advanced integrated treatment programs in people with schizophrenia. The Italian Network for Research on Psychoses previously explored, by using network analysis, the interplay among illness-related variables, personal resources, context-related factors and real-life functioning in a large sample of patients with schizophrenia. The same research network has now completed a 4-year follow-up of the original sample. In the present study, we used network analysis to test whether the pattern of relationships among all variables investigated at baseline was similar at follow-up. In addition, we compared the network structure of patients who were classified as recovered at follow-up versus those who did not recover. Six hundred eighteen subjects recruited at baseline could be assessed in the follow-up study. The network structure did not change significantly from baseline to follow-up, and the overall strength of the connections among variables increased slightly, but not significantly. Functional capacity and everyday life skills had a high betweenness and closeness in the network at follow-up, as they had at baseline, while psychopathological variables remained more peripheral. The network structure and connectivity of non-recovered patients were similar to those observed in the whole sample, but very different from those in recovered subjects, in which we found few connections only. These data strongly suggest that tightly coupled symptoms/dysfunctions tend to maintain each other's activation, contributing to poor outcome in schizophrenia. Early and integrated treatment plans, targeting variables with high centrality, might prevent the emergence of self-reinforcing networks of symptoms and dysfunctions in people with schizophrenia

The interplay among psychopathology, personal resources, context-related factors and real-life functioning in schizophrenia: stability in relationships after 4 years and differences in network structure between recovered and non-recovered patients

Improving real-life functioning is the main goal of the most advanced integrated treatment programs in people with schizophrenia. The Italian Network for Research on Psychoses previously explored, by using network analysis, the interplay among illness-related variables, personal resources, context-related factors and real-life functioning in a large sample of patients with schizophrenia. The same research network has now completed a 4-year follow-up of the original sample. In the present study, we used network analysis to test whether the pattern of relationships among all variables investigated at baseline was similar at follow-up. In addition, we compared the network structure of patients who were classified as recovered at follow-up versus those who did not recover. Six hundred eighteen subjects recruited at baseline could be assessed in the follow-up study. The network structure did not change significantly from baseline to follow-up, and the overall strength of the connections among variables increased slightly, but not significantly. Functional capacity and everyday life skills had a high betweenness and closeness in the network at follow-up, as they had at baseline, while psychopathological variables remained more peripheral. The network structure and connectivity of non-recovered patients were similar to those observed in the whole sample, but very different from those in recovered subjects, in which we found few connections only. These data strongly suggest that tightly coupled symptoms/dysfunctions tend to maintain each other's activation, contributing to poor outcome in schizophrenia. Early and integrated treatment plans, targeting variables with high centrality, might prevent the emergence of self-reinforcing networks of symptoms and dysfunctions in people with schizophrenia

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Characterization of Silicon Photomultipliers after proton irradiation up to 101410^{14} neq/cm2n_{eq}/cm^{2}

Silicon photomultipliers (SiPMs) are highly-sensitive photodetectors emerging as the technology of choice for many applications, including large high-energy physics experiments where they often are exposed to high radiation fluences. In recent years, there has been an increasing interest in assessing the performance deterioration of such detectors after the irradiation with proton or neutron, with different fluence levels. In this work, samples of different FBK SiPM technologies, made with different manufacturing technologies, were irradiated at the INFN-LNS facility (Italy) with protons reaching fluences up to about 10^14 neq/cm^2 (1 MeV neutron equivalent) and their performances were characterized in detail after about 30-days room temperature annealing. The results show a significant worsening of the primary noise (dark count rate) of the detectors, which increases with the irradiation fluence, whereas the other performance parameters like the micro-cell gain, the correlated noise probability and the photon detection efficiency do not show significant variations up to 10^11 neq/cm^2 at least. The breakdown voltage estimation after irradiation is another important aspect for a SiPM. In this contribution, we show several methods for its estimation and compare the results. We also introduced new methodologies to characterize the performance of the SiPMs when they present a very high level of noise, such as the estimation of the dark count rate based on the measured reverse current, the estimation of variations in the photon detection efficiency through the measurement of the responsivity, and the measurement of the correlated noise and the gain through the average charge in response to a pulsed light signal. Lastly, we also analyzed the spatial localization of the proton-induced defects inside the device, i.e. the defects that mostly contribute to the increase of the DCR of the device, through the emission microscopy (EMMI) technique. In particular, we analyzed the SiPMs at the single cell level, trying to identify and spatially localize the defects

Clinical Characteristics, Outcomes, and Risk Factors of Patients Hospitalized for COVID-19 across the Latest Pandemic Waves: Has Something Changed?

Despite the availability of vaccines and antivirals and the biological evolution of SARS-CoV-2, the rate of hospitalizations and deaths from COVID-19 remains high in Italy. It is crucial to understand whether and how the clinical characteristics of patients hospitalized for COVID-19 have changed over 2021–2022 and which risk factors are currently associated with adverse outcomes to develop targeted interventions. In this study, we present and compare the characteristics and outcomes of 310 patients with COVID-19 who were hospitalized between 1 August and 9 December 2021, when the Delta SARS-CoV-2 variant was prevalent (Group A), and between 3 January and 30 June 2022, when the Omicron variant was predominant (Group B). Using Survival Analysis, we estimated the cumulative 28-day hazard ratio (H.R.) of Intensive Care Unit (ICU) admission/death of patients in Group B vs. A. We built uni- and multivariate Cox regression models for the overall population and each group to identify risk factors for ICU admission/death among patient features. We found that Group B had a comparable risk of ICU admission/death (HR 1.60, 95% Confidence Interval, C.I. 1.00–2.58, p = 0.05) but a higher prevalence of elderly and co-morbid subjects than Group A. Non-invasive ventilation requirement was associated with adverse outcomes in both Group A (HR 21.03, 95% C.I. 5.34–82.80, p p p < 0.001). During the Omicron wave, elderly and co-morbid subjects had the highest risk of hospitalization and poor outcomes

Assessment of de novo copy-number variations in Italian patients with schizophrenia: Detection of putative mutations involving regulatory enhancer elements

Objectives: Variants appearing de novo in genes regulating key neurodevelopmental processes and/or in non-coding cis-regulatory elements (CREs), as enhancers, may increase the risk for schizophrenia. However, CREs involvement in schizophrenia needs to be explored more deeply. Methods: We investigated de novo copy-number variations (CNVs) in the whole-genomic DNA obtained from 46 family trios of schizophrenia probands by using the Enhancer Chip, a customised array CGH able to investigate the whole genome with a 300-kb resolution, specific disease loci at a ten-fold higher resolution, and which was highly enriched in probes in more than 1,250 enhancer elements selected from Vista Enhancer Browser. Results: In seven patients, we found de novo CNVs, two of which overlapped VISTA enhancer elements. De novo CNVs encompass genes (CNTNAP2, MAGI1, TSPAN7 and MET) involved in brain development, while that involving the enhancer element hs1043, also includes ZIC1, which plays a role in neural development and is responsible of behavioural abnormalities in Zic mutant mice. Conclusions: These findings provide further evidence for the involvement of de novo CNVs in the pathogenesis of schizophrenia and suggest that CNVs affecting regulatory enhancer elements could contribute to the genetic vulnerability to the disorder

Accuracy of self-assessment of real-life functioning in schizophrenia

A consensus has not yet been reached regarding the accuracy of people with schizophrenia in self-reporting their real-life functioning. In a large (n=618) cohort of stable, community-dwelling schizophrenia patients we sought to: (1) examine the concordance of patients' reports of their real-life functioning with the reports of their key caregiver; (2) identify which patient characteristics are associated to the differences between patients and informants. Patient-caregiver concordance of the ratings in three Specific Level of Functioning Scale (SLOF) domains (interpersonal relationships, everyday life skills, work skills) was evaluated with matched-pair t tests, the Lin's concordance correlation, Somers' D, and Bland-Altman plots with limits of agreement (LOA). Predictors of the patient-caregiver differences in SLOF ratings were assessed with a linear regression with multivariable fractional polynomials. Patients' self-evaluation of functioning was higher than caregivers' in all the evaluated domains of the SLOF and 17.6% of the patients exceeded the LOA, thus providing a self-evaluation discordant from their key caregivers. The strongest predictors of patient-caregiver discrepancies were caregivers' ratings in each SLOF domain. In clinically stable outpatients with a moderate degree of functional impairment, self-evaluation with the SLOF scale can become a useful, informative and reliable clinical tool to design a tailored rehabilitation program

Premorbid academic and social functioning in patients with schizophrenia and its associations with negative symptoms and cognition

Objective: The study aimed to explore premorbid academic and social functioning in patients with schizophrenia, and its associations with the severity of negative symptoms and neurocognitive impairment. Method: Premorbid adjustment (PA) in patients with schizophrenia was compared to early adjustment in unaffected first-degree relatives and healthy controls. Its associations with psychopathology, cognition, and real-life functioning were investigated. The associations of PA with primary negative symptoms and their two factors were explored. Results: We found an impairment of academic and social PA in patients (P ≤ 0.000001) and an impairment of academic aspects of early adjustment in relatives (P ≤ 0.01). Patients with poor PA showed greater severity of negative symptoms (limited to avolition after excluding the effect of depression/parkinsonism), working memory, social cognition, and real-life functioning (P ≤ 0.01 to ≤0.000001). Worse academic and social PA were associated with greater severity of psychopathology, cognitive impairment, and real-life functioning impairment (P ≤ 0.000001). Regression analyses showed that worse PA in the academic domain was mainly associated to the impairment of working memory, whereas worse PA in the social domain to avolition (P ≤ 0.000001). Conclusion: Our findings suggest that poor early adjustment may represent a marker of vulnerability to schizophrenia and highlight the need for preventive/early interventions based on psychosocial and/or cognitive programs