Performance optimization of detector electronics for millimeter laser ranging

The front-end electronic circuitry plays a fundamental role in determining the performance actually obtained from ultrafast and highly sensitive photodetectors. We deal here with electronic problems met working with microchannel plate photomultipliers (MCP-PMTs) and single photon avalanche diodes (SPADs) for detecting single optical photons and measuring their arrival time with picosecond resolution. The performance of available fast circuits is critically analyzed. Criteria for selecting the most suitable electronics are derived and solutions for exploiting the detector performance are presented and discussed

How to squeeze high quantum efficiency and high time resolution out of a SPAD

We address the issue whether Single-Photon Avalanche Diodes (SPADs) can be suitably designed to achieve a trade-off between quantum efficiency and time resolution performance. We briefly recall the physical mechanisms setting the time resolution of avalanche photodiodes operated in single-photon counting, and we give some criteria for the design of SPADs with a quantum efficiency better than l0 percent at 1064 nm together with a time resolution below 50 ps rms

Gamma-ray Tracking with Segmented HPGe Detectors

This paper gives a brief overview of the technical progress that can be achieved with the newly available segmented HPGe detectors. Gamma-ray tracking detectors are a new generation of HPGe detectors which are currently being developed to improve significantly the efficiency and resolving power of the 4 … germanium detectors arrays for high-precision ∞-ray spectroscopy. They consist of highly segmented HPGe detectors associated with fast digital front-end electronics. Through the pulse-shape analysis of the signals it is possible to extract the energy, timing and spatial information on the few interactions a ∞-ray undergoes in the HPGe detector. The tracks of the ∞-rays in the HPGe detector can then be reconstructed in three dimensions based on the Compton scattering formula. Such a detector has been used for the first time during an in-beam experiment. The ∞-decay of the Coulomb excitation of a 56 Fe nucleus was measured with the highly segmented MARS prototype positioned at 135 degree. The energy resolution has been improved by a factor of 3 as compared to standard HPGe detectors due to very precise Doppler correction based on knowledge of the ∞-ray track. I Introduction The future facilities for radioactive beams will allow, for the first time, the exploration of a new large area of the nuclear landscape. In connection with the study of the ∞-radiation, it is important to point out that the intensity of such radioactive beams is expected to be much smaller than that of stable beams, Doppler Effects in many experiments are expected to be much stronger and an intense background of X-rays could be present. Consequently, a new generation of powerful HPGe arrays with segmented detectors is being designed. Both in USA and in Europe several projects, based on segmented HPGe detectors, have already started and are in an advanced status of realization. The objective of the more recent R&D efforts is to improve the total efficiency by removing the BGO shields without affecting the P/T ratio with the use of the tracking technique, namely the reconstruction of the ∞-ray path to identify the ∞-incident direction (for the Doppler correction), the removal of the background and to check whether or not the ∞ was fully absorbed in the array. Such development implies unprecedented R&D efforts where completely new technology has to be applied, tested or developed in all the constituents of an HPGe array, from the detector to the front-end electronics. The typical feature of the energy deposition of a ∞-ray is that of interacting in a limited number of positions. ∞-tracking of this hits is a very challenging and ambitious task. First, one has to identify, isolate and localize each hit inside a segmented detector with pulse shape analysis based on the study of the physical mechanism of the pulse generation or with Artificial Intelligence techniques (like Neural Networks or Genetic Algorithm [1]) of the direct and induced electrical pulses produced by every interacting ∞-rays. Second, a tracking algorithm has to reconstruct the real trajectory from the list of interaction points through statistical techniques. The result is expected to be the complete reconstruction of the track of the incident ∞, namely the complete description of the interacting ∞-ray. Worldwide efforts have been done using simulations and proof-of-principle measurements and turned out to be successful. The feasibility of the entire process of ∞ray tracking is demonstrated in this paper based on an experiment, done at the LNL in Italy, using the MARS prototype detector

Enhanced immunological recovery with early start of antiretroviral therapy during acute or early HIV infection–results of Italian Network of ACuTe HIV InfectiON (INACTION) retrospective study

ABSTRACT Background: Viral load peak and immune activation occur shortly after exposure during acute or early HIV infection (AEHI). We aimed to define the benefit of early start of antiretroviral treatment (ART) during AEHI in terms of immunological recovery, virological suppression, and treatment discontinuation. Setting: Patients diagnosed with AEHI (Fiebig stages I-V) during 2008-2014 from an analysis of 20 Italian centers. Methods: This was an observational, retrospective, and multicenter study. We investigated the ef- fect of early ART (defined as initiation within 3 months from AEHI diagnosis) on time to virolog- ical suppression, optimal immunological recovery (defined as CD4 count ≥ 500/μL, CD4 ≥ 30%, and CD4/CD8 ≥ 1), and first-line ART regimen discontinuation by Cox regression analysis. Results: There were 321 patients with AEHI included in the study (82.9% in Fiebig stage III-V). At diagnosis, the median viral load was 5.67 log10 copies/mL and the median CD4 count was 456 cells/μL. Overall, 70.6% of patients started early ART (median time from HIV diagnosis to ART initiation 12 days, IQR 6-27). Higher baseline viral load and AEHI diagnosis during 2012-2014 were independently associated with early ART. HBV co-infection, baseline CD4/CD8 ≥ 1, lower baseline HIV-RNA, and AEHI diagnosis in recent years (2012-2014) were independently associ- ated with a shorter time to virological suppression. Early ART emerged as an independent predic- tor of optimal immunological recovery after adjustment for baseline CD4 (absolute and percent- age count) and CD4/CD8 ratio. The only independent predictor of first-line ART discontinuation was an initial ART regimen including > 3 drugs. Conclusions: In a large cohort of well-characterized patients with AEHI, we confirmed the ben- eficial role of early ART on CD4+ T-cell recovery and on rates of CD4/CD8 ratio normalization. Moreover, we recognized baseline CD4/CD8 ratio as an independent factor influencing time to virological response in the setting of AEHI, thus giving new insights into research of immunolog- ical markers associated with virological control

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor