New developments from the TORCH R&D project Jones, T.; Bhasin, S.; Blake, T. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
01/2023, Letnik:
1045
Journal Article
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TORCH is a large-area and high-precision time-of-flight detector, designed to provide charged particle identification over a 2–20GeV/c momentum range. The TORCH detector comprises a 10 mm thick ...quartz radiator, instrumented with photon detectors, which precisely time and measure the arrival positions of the Cherenkov photons. The photon detectors are micro-channel plate photo-multiplier tubes (MCP-PMTs) comprising a finely segmented anode of 64 × 64 anode pads, electronically ganged into 64 × 8 pixels, over a 53 × 53mm2 area, an excellent intrinsic time resolution of ∼ 30ps, and a long lifetime of up to ≳ 5C/cm2. The current version of the MCP-PMTs used by TORCH have been developed with an industrial partner, Photek Ltd, to satisfy the stringent requirements of the detector. The TORCH R&D programme has successfully demonstrated the detector concept through extensive laboratory and beam tests. A TORCH prototype has been constructed and has yielded encouraging results when exposed to low momentum charged hadrons. Characteristic patterns of Cherenkov photons have been recorded, illustrating the required spatial accuracy and timing resolution of 70 ps per photon. Both laboratory and beam test results are approaching the design goals of the TORCH detector.
This thesis presents two complementary research studies, linked by the LHCb experiment. A first analysis of the angular distribution of the B+→π + μ-μ+decay with LHCb Run 1 and 2 data is presented, ...using the Feldman-Cousins approach to ensure correct coverage of the angular observables measured, AFB and FH. This decay is a rare b! d quark avour changing neutral current process. The analysis is at an advanced stage and blind at the time of writing of this work. The analysis strategy is tested on control modes and pseudo-experiments. Sources of systematic uncertainties are identified and their effects evaluated. In addition, studies for the R&D effort for the development of a new time-of-flight Cherenkov detector, TORCH, proposed for the next LHCb upgrade are presented. The proposed design uses MCP-PMTs to measure single photon time. The TORCH MCP-PMT is characterised with studies of uniformity and gain. The single photon time resolution of the TORCH MCP-PMT coupled to readout electronics has been measured, resulting in (47:5 0:7) ps, meeting the TORCH design requirement.
SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pneumonia, referred to as COVID-19 (Coronavirus Disease 19), is a public health emergency as it carries high morbidity, mortality, ...and has no approved specific pharmacological treatments. In this case series, we aimed to report preliminary data obtained with anti-complement C5 therapy with eculizumab in COVID-19 patients admitted to intensive care unit (ICU) of ASL Napoli 2 Nord.
This is a case series of patients with a confirmed diagnosis of SARS-CoV2 infection and severe pneumonia or ARDS who were treated with up to 4 infusions of eculizumab as an off-label agent. Patients were also treated with anticoagulant therapy with Enoxaparin 4000 IU/day via subcutaneous injection, antiviral therapy with Lopinavir 800 mg/day + Ritonavir 200 mg/day, hydroxychloroquine 400 mg/day, ceftriaxone 2 g/day IV, vitamine C 6 g/day for 4 days, and were on Non-Invasive Ventilation (NIV).
We treated four COVID-19 patients admitted to the intensive care unit because of severe pneumonia or ARDS. All patients successfully recovered after treatment with eculizumab. Eculizumab induced a drop in inflammatory markers. Mean C Reactive Protein levels dropped from 14.6 mg/dl to 3.5 mg/dl and the mean duration of the disease was 12.8 days.
Eculizumab has the potential to be a key player in treatment of severe cases of COVID-19. Our results support eculizumab use as an off-label treatment of COVID-19, pending confirmation from the ongoing SOLID-C19 trial.
Diamond is considered as a very promising material for the development of devices for radiation detection. Unlike other conventional photoconductive detectors diamond-based devices should provide ...high discrimination between UV and visible radiation. In this work we present the electro-optical properties of devices based on randomly oriented diamond films, synthesized in a microwave plasma enhanced chemical vapor deposition reactor. A comparative study on devices with coplanar interdigitated Cr/Au electrodes (with different interelectrode pitches) made of films grown simultaneously on intrinsic and p-doped silicon (100) substrates has been performed. The chemical–structural, morphological, electrical and optical properties of ROD films have been studied. In particular, the optical response has been measured in air using a Xe flash lamp coupled with an optical quartz fiber and a properly tailored front-end electronics based on a charge sensitive amplifier. Experimental results gave indications on how the device performances are dependent on the two types of employed substrates.
► Coplanar interdigitated electrodes design plays a strong role in electrical and photo electrical detectors parameters. ► We show a comparative study on comb electrodes obtained for devices based on randomly oriented diamond films. ► Randomly Oriented Diamond films have been grown on p type and i type silicon substrate with different electrode pattern geometry. ► Dark current, capacitance and photo detector efficiency for each device have been measured. ► The devices show good UV to visible signal ratio, especially for the films with an interelectrode gap comparable with the the film thickness.
Abstract Introduction Left bundle branch area pacing (LBBAP) has become, in the last years, the preferred method for physiological pacing due to a wider target area, optimal pacing and sensing ...thresholds, and stable parameters over time. LBBAP ensures rapid and synchronous left ventricular (LV) activation through the left-sided conduction system. On the other hand, there is little data on right ventricular (RV) activation in LBBAP. The purpose of this study was to evaluate the impact of LBBAP on the right heart anatomy and function over a mid-term follow-up period. Material and methods All consecutive patients with successful LBBAP for bradyarrhythmic indications between February 2021 and July 2022 at our institution were eligible for this study. Left bundle branch capture was defined as a paced QRS complex of right bundle branch block morphology, and proof of transition from non-selective to selective capture with differential pacing maneuvers. To avoid confounders, patients with LV ejection fraction below 40% and with severe valvular disease were excluded. In the end, 57 patients were prospectively evaluated. Patient and procedural characteristics were recorded at baseline and follow-up. Also, right atrial (RA) volume, RV basal diameter, tricuspid annulus peak systolic elevation (TAPSE), RV S` wave (RVS`W), and tricuspid regurgitation (TR) were evaluated before the procedure and at the end of the follow-up period. Results The mean age of the patients was 68.9± 10 years, and 70% were males. 29.8% had a baseline right bundle branch block, and 22.8% had a left bundle branch block morphology. The baseline LV ejection fraction was 54.3 ± 9.9 %. The paced QRS duration was similar to the baseline values (128.5 ± 16.3 vs. 134.4 ± 30.4 msec, p=0.119). The pacing and sensing thresholds were 0.7 ± 0.3 V at 0.4 ms pulse duration and 9.7 ± 4.2 mV, respectively. The mean LV activation time (measured as the R wave peak time in V6) was 80.9 ± 12 msec, and the mean RV activation time (measured as the difference between QRS duration and LV activation time) was 51.9 ± 24.2 msec. The patients were followed over a mean period of 591.2 ± 150.3 days. There were no complications over the follow-up period that led to pacing interruption. The follow-up pacing (0.6 ± 0.2 V, p=0.003) and sensing (11.7 ± 6 mV, p= 0.023) thresholds showed significant improvement compared to the procedural values. The right heart echocardiographic evaluation showed non-statistically significant changes between the follow-up and the baseline values for RA volumes (57.9 ± 33.7 vs. 51.5 ± 28.4 ml, p=0.122), RV basal diameter (32.8 ± 5.4 vs. 31.8 ± 6.4 mm, p=0.31), RVS`W (12.8 ± 3.2 vs. 12.85 ± 2.7 cm/sec, p=0.933), and TR (1.8±0.8 vs. 2±1, p=0.07). On the other hand, there was a significant improvement in the TAPSE (22.2±4.3 vs. 20.7±3.6 mm, p=0.021). Conclusions LBBAP was associated with preserved dimensions and function of the right cardiac chambers over a medium-term follow-up period.
Summary
Background
Gastro‐oesophageal reflux disease (GERD) may contribute to the onset of chronic cough (CC); however, the multichannel intraluminal impedance‐pH (MII‐pH) monitoring is often within ...the normal range and the response to proton pump inhibitors (PPIs) unsatisfactory. The measure of impedance baseline (IB) increases the sensitivity of MII‐pH in patients with typical symptoms.
Aim
To evaluate the role of MII‐pH variables, including IB, in predicting PPI response and to define the characteristics of the reflux pattern in CC patients.
Methods
Prospectively selected CC patients suspected GERD‐related underwent MII‐pH monitoring and, therefore, received a double dose of PPIs for at least 6 weeks. Patients filled symptom scores before MII‐pH and after PPI therapy. MII‐pH data were compared with those obtained in 60 non‐erosive reflux disease patients with typical symptoms.
Results
A total of 156 CC patients entered the study: 68 (43.5%) responders and 88 (56.5%) nonresponders to PPIs. The number of reflux episodes was significantly higher in CC compared with that in typical symptoms patients. Nonresponder CC patients with a pathological acid exposure time (AET) and/or IB value were 43/88 (49%), while 15/88 (17%) presented only pathological AET (P < 0.001). CC patients with a pathological AET or IB, or with both a pathological AET and IB, showed a probability of PPI response twofold greater than patients with normal AET and IB.
Conclusions
The presence of a pathological AET or pathological IB in CC patients is associated with a greater probability of PPI response. IB is a promising variable in patients with CC, as it increases the diagnostic yield of MII‐pH and allows confirmation of the GERD diagnosis in these patients.
Previous ecological studies suggest the existence of possible interplays between the exposure to air pollutants and SARS-CoV-2 infection. Confirmations at individual level, however, are lacking. To ...explore the relationships between previous exposure to particulate matter < 10 μm (PM
10
) and nitrogen dioxide (NO
2
), the clinical outcome following hospital admittance, and lymphocyte subsets in COVID-19 patients with pneumonia. In 147 geocoded patients, we assessed the individual exposure to PM
10
and NO
2
in the 2 weeks before hospital admittance. We divided subjects according to the clinical outcome (i.e., discharge at home vs in-hospital death), and explored the lymphocyte-related immune function as an index possibly affecting individual vulnerability to the infection. As compared with discharged subjects, patients who underwent in-hospital death presented neutrophilia, lymphopenia, lower number of T CD45, CD3, CD4, CD16/56 + CD3 + , and B CD19 + cells, and higher previous exposure to NO
2
, but not PM
10
. Age and previous NO
2
exposure were independent predictors for mortality. NO
2
concentrations were also negatively related with the number of CD45, CD3, and CD4 cells. Previous NO
2
exposure is a co-factor independently affecting the mortality risk in infected individuals, through negative immune effects. Lymphopenia and altered lymphocyte subsets might precede viral infection due to nonmodifiable (i.e., age) and external (i.e., air pollution) factors. Thus, decreasing the burden of air pollutants should be a valuable primary prevention measure to reduce individual susceptibility to SARS-CoV-2 infection and mortality.
HIV-1 persistence during ART is due to the establishment of long-lived viral reservoirs in resting immune cells. Using an NHP model of barcoded SIVmac239 intravenous infection and therapeutic dosing ...of anti-TGFBR1 inhibitor galunisertib (LY2157299), we confirm the latency reversal properties of in vivo TGF-β blockade, decrease viral reservoirs and stimulate immune responses. Treatment of eight female, SIV-infected macaques on ART with four 2-weeks cycles of galunisertib leads to viral reactivation as indicated by plasma viral load and immunoPET/CT with a
Cu-DOTA-F(ab')
-p7D3-probe. Post-galunisertib, lymph nodes, gut and PBMC exhibit lower cell-associated (CA-)SIV DNA and lower intact pro-virus (PBMC). Galunisertib does not lead to systemic increase in inflammatory cytokines. High-dimensional cytometry, bulk, and single-cell (sc)RNAseq reveal a galunisertib-driven shift toward an effector phenotype in T and NK cells characterized by a progressive downregulation in TCF1. In summary, we demonstrate that galunisertib, a clinical stage TGF-β inhibitor, reverses SIV latency and decreases SIV reservoirs by driving T cells toward an effector phenotype, enhancing immune responses in vivo in absence of toxicity.
In recent years, improvement of Health-Related Quality of Life (HRQoL) in Ulcerative colitis (UC) has become a relevant measure for treatment efficacy.
We report results from a multicenter ...prospective study in Italy investigating HRQoL in adult patients with UC treated with golimumab (GLM). Patients who had shown clinical response after a 6-week induction phase (w0), were followed for an additional 48 weeks (w48) (total 54-week treatment).
Of the 159 patients enrolled 90 completed the study. Compared to values at the beginning of treatment (n = 137), significant improvements were observed for mean total Inflammatory Bowel Disease Questionnaire (IBDQ) scores at w0 (168.5) and w48 (181.7). Patients with baseline PMS above the median tended to have greater improvements in IBDQ at w0 (OR 2.037, p = 0.033) and w48 (OR 3.292, p = 0.027). Compared to beginning of GLM treatment, the mean Full Mayo Score (FMS) decreased by 5.9 points at w48, while mean Partial Mayo Score (PMS) decreased by 3.9 points at w0 and by 4.9 points at w48.
GLM improved HRQoL, disease activity and inflammatory biomarkers in UC patients with moderate-to-severely active disease. The greater the burden of disease activity at baseline, the greater the improvement of HRQoL after 24 and 48 weeks of treatment.
The high prevalence of primary aldosteronism among hypertensives justifies large scale screening by the aldosterone-renin ratio; however, this test is subject to several variables responsible for ...false-positive results. Functional tests to confirm autonomous aldosterone secretion are commonly used, with the fludrocortisone suppression test considered the gold standard, and saline infusion or captopril challenge, the most practical. However, each of these tests has sub-optimal sensitivity and specificity and none has been so far prospectively validated by comparing the results with the lateralization by adrenal vein sampling and the results of surgery. Their role in confirming the diagnosis of primary aldosteronism due to unilateral adenoma remains incompletely resolved.
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