Fast incremental expectation maximization (FIEM) is a version of the EM framework for large datasets. In this paper, we first recast FIEM and other incremental EM type algorithms in the
Stochastic ...Approximation within EM
framework. Then, we provide nonasymptotic bounds for the convergence in expectation as a function of the number of examples
n
and of the maximal number of iterations
K
max
. We propose two strategies for achieving an
ϵ
-approximate stationary point, respectively with
K
max
=
O
(
n
2
/
3
/
ϵ
)
and
K
max
=
O
(
n
/
ϵ
3
/
2
)
, both strategies relying on a random termination rule before
K
max
and on a constant step size in the Stochastic Approximation step. Our bounds provide some improvements on the literature. First, they allow
K
max
to scale as
n
which is better than
n
2
/
3
which was the best rate obtained so far; it is at the cost of a larger dependence upon the tolerance
ϵ
, thus making this control relevant for small to medium accuracy with respect to the number of examples
n
. Second, for the
n
2
/
3
-rate, the numerical illustrations show that thanks to an optimized choice of the step size and of the bounds in terms of quantities characterizing the optimization problem at hand, our results design a less conservative choice of the step size and provide a better control of the convergence in expectation.
Some COVID-19 survivors suffer from persistent pulmonary function impairment, but the extent and associated factors are unclear. This study aimed to characterize pulmonary function impairment three ...to five months after hospital discharge and the association with disease severity. Survivors of COVID-19 after hospitalization to the VieCuri Medical Centre between February and December 2020 were invited for follow-up, three to five months after discharge. Dynamic and static lung volumes, respiratory muscle strength and diffusion capacity were measured. The cohort comprised 257 patients after a moderate (n = 33), severe (n = 151) or critical (n = 73) COVID-19 infection with a median follow-up of 112 days (interquartile range 96-134 days). The main sequelae included reduced diffusion capacity (36%) and reduced maximal expiratory pressure (24%). Critically ill patients were more likely to have reduced diffusion capacity than moderate (OR 8.00, 95% CI 2.46-26.01) and severe cases (OR 3.74, 95% CI 1.88-7.44) and lower forced vital capacity (OR 3.29, 95% CI 1.20-9.06) compared to severe cases. Many COVID-19 survivors, especially after a critical disease course, showed pulmonary function sequelae, mainly DLCO impairments, three to five months after discharge. Monitoring is needed to investigate the persistence of these symptoms and the longer-term implications of the COVID-19 burden.
Abstract A significant proportion of COVID-19 survivors still experience a reduced diffusion capacity three and twelve months after discharge. We aimed to compare pulmonary function trajectories ...between hospitalized COVID-19 patients with pre-existing respiratory disease (PRD) and patients without pre-existing respiratory disease (Non-PRD) at three and twelve months after hospital discharge. This single-centre retrospective cohort study included COVID-19 patients admitted to the VieCuri Medical Centre (Venlo, the Netherlands) between February and December 2020 that were invited to the outpatient clinic at three and twelve months after discharge. During this visit, pulmonary function tests were performed and impairments were based on lower limit of normal. Data of 239 patients were analysed (65% male, 66 ± 10 years, and 26% with a history of respiratory disease). Three months after discharge, 49% and 64% of the Non-PRD patients (n = 177) and PRD patients (n = 62) had a low diffusion capacity, respectively. This improved over time in Non-PRD patients ( p = 0.003), but not in PRD patients ( p = 0.250). A low diffusion capacity was still observed in 34% and 57% of the Non-PRD and PRD group, respectively, twelve months after discharge. Pulmonary function impairments, mainly a reduced diffusion capacity, are observed among hospitalized COVID-19 patients with PRD and Non-PRD, at three and twelve months follow-up. Although diffusion capacity impairments restore over time in Non-PRD patients, poor recovery was observed among PRD patients.
Episcleral plaque brachytherapy (EPB) planning is conventionally based on approximations of the implant geometry with no volumetric imaging following plaque implantation. We have developed an ...MRI-based technique for EPB treatment planning and dose delivery verification based on the actual patient-specific geometry.
MR images of 6 patients, prescribed 85 Gy over 96 hours from Collaborative Ocular Melanoma Study-based EPB, were acquired before and after implantation. Preimplant and postimplant scans were used to generate "preplans" and "postplans", respectively. In the preplans, a digital plaque model was positioned relative to the tumor, sclera, and nerve. In the postplans, the same plaque model was positioned based on the imaged plaque. Plaque position, point doses, percentage of tumor volume receiving 85 Gy (V
), and dose to 100% of tumor volume (D
) were compared between preplans and postplans. All isodose plans were computed using TG-43 formalism with no heterogeneity corrections.
Shifts and tilts of the plaque ranged from 1.4 to 8.6 mm and 1.0 to 3.8 mm, respectively. V
was ≥97% for 4 patients. D
for preplans and postplans ranged from 83 to 118 Gy and 45 to 110 Gy, respectively. Point doses for tumor apex and base were all found to decrease from the preimplant to the postimplant plan, with mean differences of 16.7 ± 8.6% and 30.5 ± 11.3%, respectively.
By implementing MRI for EPB, we eliminate reliance on approximations of the eye and tumor shape and the assumption of idealized plaque placement. With MRI, one can perform preimplant as well as postimplant imaging, facilitating EPB treatment planning based on the actual patient-specific geometry and dose-delivery verification based on the imaged plaque position.
Little is known about the humoral immune response against DNA prime-recombinant adenovirus 5 (rAd5) boost HIV vaccine among HIV-infected patients on long-term suppressive antiretroviral therapy ...(ART). Previous studies emphasized cellular immune responses; however, current research suggests both cellular and humoral responses are likely required for a successful therapeutic vaccine. Thus, we aimed to understand antibody response and function induced by vaccination of ART-treated HIV-1-infected patients with immune recovery. All subjects participated in EraMune 02, an open-label randomized clinical trial of ART intensification followed by a six plasmid DNA prime (envA, envB, envC, gagB, polB, nefB) and rAd5 boost HIV vaccine with matching inserts. Antibody binding levels were determined with a recently developed microarray approach. We also analyzed neutralization efficiency and antibody-dependent cellular cytotoxicity (ADCC). We found that the DNA prime-rAd5 boost vaccine induced a significant cross-clade HIV-specific antibody response, which correlated with antibody neutralization efficiency. However, despite the increase in antibody binding levels, the vaccine did not significantly stimulate neutralization or ADCC responses. This finding was also reflected by a lack of change in total CD4+ cell associated HIV DNA in those who received the vaccine. Our results have important implications for further therapeutic vaccine design and administration, especially in HIV-1 infected patients, as boosting of preexisting antibody responses are unlikely to lead to clearance of latent proviruses in the HIV reservoir.
The persistence of symptoms beyond three months after COVID-19 infection, often referred to as post-COVID-19 condition (PCC), is commonly experienced. It is hypothesized that PCC results from ...autonomic dysfunction with decreased vagal nerve activity, which can be indexed by low heart rate variability (HRV). The aim of this study was to assess the association of HRV upon admission with pulmonary function impairment and the number of reported symptoms beyond three months after initial hospitalization for COVID-19 between February and December 2020. Follow-up took place three to five months after discharge and included pulmonary function tests and the assessment of persistent symptoms. HRV analysis was performed on one 10 s electrocardiogram obtained upon admission. Analyses were performed using multivariable and multinomial logistic regression models. Among 171 patients who received follow-up, and with an electrocardiogram at admission, decreased diffusion capacity of the lung for carbon monoxide (DLCO) (41%) was most frequently found. After a median of 119 days (IQR 101-141), 81% of the participants reported at least one symptom. HRV was not associated with pulmonary function impairment or persistent symptoms three to five months after hospitalization for COVID-19.
Abstract
Myeloperoxidase (MPO) is a pro-oxidant enzyme involved in inflammation, and the measurement of its activity in biological samples has emerged essential for laboratory and clinical ...investigations. We will describe a new method which combines the SIEFED (specific immunological extraction followed by enzymatic detection) and ELISA (ELISAcb) techniques to measure the active and total amounts of MPO on the same human sample and with the same calibration curve, as well as to define an accurate ratio between both the active and total forms of the enzyme.
The SIEFED/ELISAcb method consists of the MPO extraction from aqueous or biological samples by immobilized anti-MPO antibodies coated onto microplate wells. After a washing step to eliminate unbound material, the activity of MPO is measured in situ by adding a reaction solution (SIEFED). Following aspiration of the reaction solution, a secondary anti-MPO antibody is added into the wells and the ELISAcb test is carried out in order to measure the total MPO content.
To validate the combined method, a comparison was made with SIEFED and ELISA experiments performed separately on plasma samples isolated from human whole blood, after a neutrophil stimulation.
The SIEFED/ELISAcb provides a suitable tool for the measurement of specific MPO activity in biological fluids and for the estimation of the inhibitory potential of a fluid. The method can also be used as a pharmacological tool to make the distinction between a catalytic inhibitor, which binds to MPO and inhibits its activity, and a steric inhibitor, which hinders the enzyme and prevents its immunodetection.
The SIEFED (“Specific Immunological Extraction Followed by Enzymatic Detection”) method already developed for the specific detection of the activity of equine myeloperoxidase (MPO) was adapted for ...the specific measurement of active human MPO in biological fluids or tissue extracts. The method consists of the extraction of MPO from aqueous solutions by immobilized anti-MPO antibodies followed by a washing (to eliminate the extraction medium and the biological fluid with their possible interfering molecules) and the measurement of the activity of MPO with a detection system containing a fluorogenic substrate, H
2O
2 and nitrite ions as reaction enhancer. The SIEFED was applied to study active MPO in human biological fluids (plasma, bronchoalveolar lavage fluid and supernatant from carotids extracts). The SIEFED for human MPO has a sensitivity limit of 0.080
mU/mL and showed good precision with intra- and inter-assay coefficients of variation below 10 and 20% respectively within a broad range of MPO activities establish from 0.156 to 473
mU/mL. The SIEFED for human MPO will be useful for the specific detection of active MPO in complex fluids and can be complementary to an ELISA to determine an active/total MPO ratio in healthy volunteers and patients especially in case of chronic or acute inflammatory diseases.
Purpose
Arterial embolization has been shown to be effective and safe for the management of bleeding, especially for postpartum and pelvic traumatic bleeding. We propose to evaluate the proof of ...concept of feasibility and effectiveness of arterial embolization with absorbable and non-absorbable sutures in a porcine model.
Materials and Methods
In the acute setting (
n
= 1), several different arteries (mesenteric, splenic, pharyngeal, kidney) were embolized using non-absorbable sutures (NAS): Mersutures
™
braided sutures (polyethylene terephthalate). In the chronic setting (
n
= 3), only lower pole renal arteries were embolized. On the right side, NAS was used, whereas on the left side embolization was realized with absorbable suture (AS): Vicryl
®
braided suture (polyglactin 910). The chronic group was followed for 3 months. The pigs received contrast-enhanced CT the day before embolization (D-1), after the embolization (D0), at 1 month and 3 months after embolization (M1 and M3); digital subtraction angiography (DSA) was done at D0 and M3 and histological analysis at M3.
Results
All vascular targets were effectively embolized without any pre- or postoperative complications. Both DSAs and CTs at M3 showed a 100% recanalization rate for the AS embolization and a partial reversal rate for the NAS embolization. A renal hypotrophy in the embolized region was observed during both the M1 and M3 scans for both sutures (AS and NAS) with a clear hypotrophy for the NAS embolized kidney.
Conclusion
Embolization by AS and NAS (FAIR-Embo) is a feasible and effective treatment which opens up the possibility of global use of this inexpensive and widely available embolization agent.
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