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Background and Objectives
In Canada, men having sex with men (MSM) are deferred for 3 months from last sexual contact to reduce human immunodeficiency virus (HIV) risk to recipients. The aim of this paper was to model the Canadian residual risk of HIV‐positive source plasma incorporating pathogen inactivation (PI) under no MSM deferral scenarios for apheresis plasma donations.
Materials and Methods
A combined Bayesian network (BN) and Monte Carlo approach were implemented to estimate the HIV residual risk under 3‐month deferral compared with no deferral without quarantine scenarios for MSM donors. Models involve the stochastic generation of donation and its infection status based on its corresponding simulated donor profile. Viral load reduction conferred by PI used by source plasma fractionators was simulated. Model parameters were derived from Héma‐Québec and Canadian Blood Services data, viral loads in a large sample of HIV‐positive US blood donors, CSL Behring documentation and from published data.
Results
In the most likely scenario for the 3‐month deferral model, there were 2.71 positive donations per 1,000,000 donations (95% confidence interval [CI] 2.63–2.78). For the no‐deferral model, there were 3.01 positive donations per 1,000,000 donations (95% CI 2.94–3.09). For both scenarios, the risk of having an infectious pool was 0 in 300,000 pools (95% CI 0–0.0000123) after consideration of PI.
Conclusion
Based on simulation results, there would be a negligible HIV residual risk associated with the removal of a time‐based MSM deferral without quarantine for source plasma incorporating PI.
The challenge to reach 10 ps coincidence time resolution (CTR) in time-of-flight positron emission tomography (TOF-PET) is triggering major efforts worldwide, but timing improvements of scintillation detectors will remain elusive without depth-of-interaction (DOI) correction in long crystals. Nonetheless, this momentum opportunely brings up the prospect of a fully time-based DOI estimation since fast timing signals intrinsically carry DOI information, even with a traditional singleended readout. Consequently, extracting features of the detected signal time distribution could uncover the spatial origin of the interaction and in return, provide enhancement on the timing precision of detectors. We demonstrate the validity of a time-based DOI estimation concept in two steps. First, experimental measurements were carried out with current LSO:Ce:Ca crystals coupled to FBK NUV-HD SiPMs read out by fast high-frequency electronics to provide new evidence of a distinct DOI effect on CTR not observable before with slower electronics. Using this detector, a DOI discrimination using a double-threshold scheme on the analog timing signal together with the signal intensity information was also developed without any complex readout or detector modification. As a second step, we explored by simulation the anticipated performance requirements of future detectors to efficiently estimate the DOI and we proposed four estimators that exploit either more generic or more precise features of the DOI-dependent timestamp distribution. A simple estimator using the time difference between two timestamps provided enhanced CTR. Additional improvements were achieved with estimators using multiple timestamps (e.g. kernel density estimation and neural network) converging to the Cramér-Rao lower bound developed in this work for a time-based DOI estimation. This two-step study provides insights on current and future possibilities in exploiting the timing signal features for DOI estimation aiming at ultra-fast CTR while maintaining detection efficiency for TOF PET.
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