Full L-1-regularized Traction Force Microscopy over whole cells

Traction Force Microscopy (TFM) is a widespread technique to estimate the tractions that cells exert on the surrounding substrate. To recover the tractions, it is necessary to solve an inverse problem, which is ill-posed and needs regularization to make the solution stable. The typical regularization scheme is given by the minimization of a cost functional, which is divided in two terms: the error present in the data or data fidelity term; and the regularization or penalty term. The classical approach is to use zero-order Tikhonov or L2-regularization, which uses the L2-norm for both terms in the cost function. Recently, some studies have demonstrated an improved performance using L1-regularization (L1-norm in the penalty term) related to an increase in the spatial resolution and sensitivity of the recovered traction field. In this manuscript, we present a comparison between the previous two regularization schemes (relying in the L2-norm for the data fidelity term) and the full L1-regularization (using the L1-norm for both terms in the cost function) for synthetic and real data. Our results reveal that L1-regularizations give an improved spatial resolution (more important for full L1-regularization) and a reduction in the background noise with respect to the classical zero-order Tikhonov regularization. In addition, we present an approximation, which makes feasible the recovery of cellular tractions over whole cells on typical full-size microscope images when working in the spatial domain. The proposed full L1-regularization improves the sensitivity to recover small stress footprints. Moreover, the proposed method has been validated to work on full-field microscopy images of real cells, what certainly demonstrates it is a promising tool for biological applications.status: publishe

The impact of surgical strategy and rifampin on treatment outcome in Cutibacterium periprosthetic joint infections.

BACKGROUND Cutibacterium species are common pathogens in periprosthetic joint infections (PJI). These infections are often treated with β-lactams or clindamycin as monotherapy, or in combination with rifampin. Clinical evidence supporting the value of adding rifampin for treatment of Cutibacterium PJI is lacking. MATERIALS/METHODS In this multicenter retrospective study, we evaluated patients with Cutibacterium PJI. The primary endpoint was clinical success, defined by the absence of infection relapse or new infection within a minimal follow-up of 12 months. We used Fisher's exact tests and Cox proportional hazards models to analyze the effect of rifampin and other factors on clinical success after PJI. RESULTS We included 187 patients (72.2% male, median age 67 years) with a median follow-up of 36 months. The surgical intervention was two-stage exchange in 95 (50.8%), one-stage exchange in 51 (27.3%), debridement and implant retention (DAIR) in 34 (18.2%), and explantation without reimplantation in 7 (3.7%). Rifampin was included in the antibiotic regimen in 81 (43.3%) cases. Infection relapse occurred in 28 (15.0%), and new infection in 13 (7.0%) cases. In the time-to-event analysis, DAIR (adjusted HR=2.15, p=0.03) and antibiotic treatment over 6 weeks (adjusted HR=0.29, p=0.0002) significantly influenced treatment failure. We observed a tentative evidence for a beneficial effect of adding rifampin to the antibiotic treatment - though not statistically significant for treatment failure (adjusted HR=0.5, p=0.07) and not for relapses (adjusted HR=0.5, p=0.10). CONCLUSIONS We conclude that a rifampin combination is not markedly superior in Cutibacterium PJI but a dedicated prospective multicenter study is needed