Wavelength conversion at 10 Gb/s by four-wave mixing over a 30-nm interval

We show that the use of a long semiconductor optical amplifier increases the error-free conversion interval of a four-wave mixing (FWM)-based wavelength converter. 30-nm wavelength down-conversion and 15-nm up-conversion have been obtained at 10 Gb/s. This result is a significant improvement over the previous best performance of a FWM-based wavelength converter and suggests that the full erbium-doped fiber amplifier bandwidth can be covered with FWM wavelength converters

30-nm wavelength conversion at 10 Gbit/s by four-wave mixing in a semiconductor optical amplifier

Four-wave mixing (FWM) in semiconductor optical amplifiers (SOAs) is currently the only available strictly transparent wavelength-conversion technique, which is not penalized by phase matching. The span of the conversion is limited primarily by conversion efficiency and signal-to-noise (SNR) issues, both of which are expected to improve with the use of longer SOAs. In this paper, we demonstrate significantly enhanced performance of long converters in a system experiment at 10 Gbit/s. The experiment shows for the first time, to our knowledge, that FWM wavelength down-conversions can span the full gain bandwidth of erbium-doped fiber amplifiers

Full-field strain analysis of bone-biomaterial systems produced by the implantation of osteoregenerative biomaterials in an ovine model

Osteoregenerative biomaterials for the treatment of bone defects are under much development, with the aim of favoring osteointegration up to complete bone regeneration. A detailed investigation of bone–biomaterial integration is vital to understand and predict the ability of such materials to promote bone formation, preventing further bone damage and supporting load-bearing regions. This study aims to characterize the ex vivo micromechanics and microdamage evolution of bone–biomaterial systems at the tissue level, combining high-resolution synchrotron microcomputed tomography, in situ mechanics and digital volume correlation. Results showed that the main microfailure events were localized close to or within the newly formed bone tissue, in proximity to the bone–biomaterial interface. The apparent nominal compressive load applied to the composite structures resulted in a complex loading scenario, mainly due to the higher heterogeneity but also to the different biomaterial degradation mechanisms. The full-field strain distribution allowed characterization of microdamage initiation and progression. The findings reported in this study provide a deeper insight into bone–biomaterial integration and micromechanics in relation to the osteoregeneration achieved in vivo for a variety of biomaterials. This could ultimately be used to improve bone tissue regeneration strategies

Optimization of the failure criterion in micro-Finite Element models of the mouse tibia for the non-invasive prediction of its failure load in preclinical applications

New treatments against osteoporosis require testing in animal models and the mouse tibia is among the most common studied anatomical sites. In vivo micro-Computed Tomography (microCT) based micro-Finite Element (microFE) models can be used for predicting the bone strength non-invasively, after proper validation against experiments. The aim of this study was to evaluate the ability of different microCT-based bone parameters and microFE models to predict tibial structural mechanical properties in compression. Twenty tibiae were scanned at 10.4 μm voxel size and subsequently tested in uniaxial compression at 0.03 mm/s until failure. Stiffness and failure load were measured from the load-displacement curves. Standard morphometric parameters were measured from the microCT images. The spatial distribution of bone mineral content (BMC) was evaluated by dividing the tibia into 40 regions. MicroFE models were generated by converting each microCT image into a voxel-based mesh with homogeneous isotropic material properties. Failure load was estimated by using different failure criteria, and the optimized parameters were selected by minimising the errors with respect to experimental measurements. Experimental and predicted stiffness were moderately correlated (R2 = 0.65, error = 14% ± 8%). Normalized failure load was best predicted by microFE models (R2 = 0.81, error = 9% ± 6%). Failure load was not correlated to the morphometric parameters and weakly correlated with some geometrical parameters (R2 < 0.37). In conclusion, microFE models can improve the current estimation of the mouse tibia structural properties and in this study an optimal failure criterion has been defined. Since it is a non-invasive method, this approach can be applied longitudinally for evaluating temporal changes in the bone strength

Effect of SR-microCT radiation on the mechanical integrity of trabecular bone using in situ mechanical testing and digital volume correlation

The use of synchrotron radiation micro-computed tomography (SR-microCT) is becoming increasingly popular for studying the relationship between microstructure and bone mechanics subjected to in situ mechanical testing. However, it is well known that the effect of SR X-ray radiation can considerably alter the mechanical properties of bone tissue. Digital volume correlation (DVC) has been extensively used to compute full-field strain distributions in bone specimens subjected to step-wise mechanical loading, but tissue damage from sequential SR-microCT scans has not been previously addressed. Therefore, the aim of this study is to examine the influence of SR irradiation-induced microdamage on the apparent elastic properties of trabecular bone using DVC applied to in situ SR-microCT tomograms obtained with different exposure times. Results showed how DVC was able to identify high local strain levels (> 10,000 µε) corresponding to visible microcracks at high irradiation doses (~ 230 kGy), despite the apparent elastic properties remained unaltered. Microcracks were not detected and bone plasticity was preserved for low irradiation doses (~ 33 kGy), although image quality and consequently, DVC performance were reduced. DVC results suggested some local deterioration of tissue that might have resulted from mechanical strain concentration further enhanced by some level of local irradiation even for low accumulated dose

Genetic immunization with the immunodominant antigen P48 of Mycoplasma agalactiae stimulates a mixed adaptive immune response in BALBc mice

A DNA vaccine against contagious agalactia was developed for the first time, encoding the P48 of Mycoplasma agalactiae. Specific immune responses elicited in BALB/c mice were evaluated. Both total IgG and IgG1 were detected in mice vaccinated with pVAX1/P48. Proliferation of mononuclear cells of the spleen, levels of gamma interferon, interleukin-12, and interleukin-2 mRNAs were enhanced in immunized animals. Results indicate that pVAX1/P48 vaccination induced both T(h)1 and T(h)2 immune responses. Nucleic acid immunization could be a new strategy against M. agalactiae infections and may be potentially used to develop vaccines for other Mycoplasma diseases

Inducing persistent flow disturbances accelerates atherogenesis and promotes thin cap fibroatheroma development in D374Y-PCSK9 hypercholesterolemic minipigs

BACKGROUND: -Although disturbed flow is thought to play a central role in the development of advanced coronary atherosclerotic plaques, no causal relationship has been established. We evaluated whether inducing disturbed flow would cause the development of advanced coronary plaques, including thin cap fibroatheroma (TCFA). METHODS AND RESULTS: -D374Y-PCSK9 hypercholesterolemic minipigs (N=5) were instrumented with an intracoronary shear-modifying stent (SMS). Frequency-domain optical coherence tomography was obtained at baseline, immediately post-stent, 19, and 34 weeks and used to compute shear stress metrics of disturbed flow. At 34 weeks, plaque type was assessed within serially-collected histological sections and co-registered to the distribution of each shear metric. The SMS caused a flow-limiting stenosis and blood flow exiting the SMS caused regions of increased shear stress on the outer curvature and large regions of low and multidirectional shear stress on the inner curvature of the vessel. As a result, plaque burden was ~3-fold higher downstream of the SMS compared to both upstream of the SMS and in the control artery (p<0.001). Advanced plaques were also primarily observed downstream of the SMS, in locations initially exposed to both low (p<0.002) and multidirectional (p<0.002) shear stress. TCFA regions demonstrated significantly lower shear stress that persisted over the duration of the study compared to other plaque types (p<0.005). CONCLUSIONS: -These data support a causal role for lowered and multidirectional shear stress in the initiation of advanced coronary atherosclerotic plaques. Persistently lowered shear stress appears to be the principal flow disturbance needed for the formation of TCFA

Percutaneous mitral valve edge-to-edge Repair: In-hospital results and 1-year follow-up of 628 patients of the 2011-2012 pilot European Sentinel Registry

The use of transcatheter mitral valve repair (TMVR) has gained widespread acceptance in Europe, but data on immediate success, safety, and long-term echocardiographic follow-up in real-world patients are still limited

Validation of calcaneus trabecular microstructure measurements by HR-pQCT

OBJECTIVE: Assessment of calcaneus microstructure using high-resolution peripheral quantitative computed tomography (HR-pQCT) might be used to improve fracture risk predictions or to assess responses to pharmacological and physical interventions. To develop a standard clinical protocol for the calcaneus, we validated calcaneus trabecular microstructure measured by HR-pQCT against 'gold-standard' micro-CT measurements. METHODS: Ten human cadaveric feet were scanned in situ using HR-pQCT (isotropic 82μm voxel size) at 100, 150 and 200ms integration times, and at 100ms integration time following removal of the calcaneus from the foot (ex vivo). Dissected portions of these bones were scanned using micro-computed tomography (micro-CT) at an isotropic 17.4μm voxel size. HR-pQCT images were rigidly registered to those obtained with micro-CT and divided into multiple 5mm sided cubes to evaluate and compare morphometric parameters between the modalities. Standard HR-pQCT measurements (derived bone volume fraction (BV/TV(d)); trabecular number, Tb.N; derived trabecular thickness, Tb.Th(d); derived trabecular spacing, Tb.Sp(d)) and corresponding micro-CT voxel-based measurements (BV/TV, Tb.N, Tb.Th, Tb.Sp) were compared. RESULTS: A total of 108 regions of interest were analysed across the 10 specimens. At all integration times HR-pQCT BV/TV(d) was strongly correlated with micro-CT BV/TV (r(2)=0.95-0.98, RMSE=1%), but BV/TV(d) was systematically lower than that measured by micro-CT (mean bias=5%). In contrast, HR-pQCT systematically overestimated Tb.N at all integration times; of the in situ scans, 200ms yielded the lowest mean bias and the strongest correlation with micro-CT (r(2)=0.61, RMSE=0.15mm(-1)). Regional analysis revealed greater accuracy for Tb.N in the superior regions of the calcaneus at all integration times in situ (mean bias=0.44-0.85mm(-1); r(2)=0.70-0.88, p<0.001 versus mean bias=0.63-1.46mm(-1); r(2)<0.10, p≥0.21 for inferior regions). Tb.Sp(d) was underestimated by HR-pQCT compared to micro-CT, but showed similar trends with integration time and the region evaluated as Tb.N. HR-pQCT Tb.Th(d) was also underestimated (mean bias=0.081-0.102mm) and moderately correlated (r(2)=0.55-0.59) with micro-CT Tb.Th, independently from the integration time. Stronger correlations, smaller biases and error were found in the scans of the calcaneus ex vivo compared to in situ. CONCLUSION: Calcaneus trabecular BV/TV(d) and trabecular microstructure, particularly in the superior region of the calcaneus, can be assessed by HR-pQCT. The highest integration time examined, 200ms, compared best with micro-CT. Weaker correlations for microstructure at inferior regions, and also with lower integration times, might limit the use of the proposed protocol, which warrants further investigation in vivo

Effects of cytokine blocking agents on hospital mortality in patients admitted to ICU with acute respiratory distress syndrome by SARS-CoV-2 infection: Retrospective cohort study

Background: The use of cytokine-blocking agents has been proposed to modulate the inflammatory response in patients with COVID-19. Tocilizumab and anakinra were included in the local protocol as an optional treatment in critically ill patients with acute respiratory distress syndrome (ARDS) by SARS-CoV-2 infection. This cohort study evaluated the effects of therapy with cytokine blocking agents on in-hospital mortality in COVID-19 patients requiring mechanical ventilation and admitted to intensive care unit. Methods: The association between therapy with tocilizumab or anakinra and in-hospital mortality was assessed in consecutive adult COVID-19 patients admitted to our ICU with moderate to severe ARDS. The association was evaluated by comparing patients who received to those who did not receive tocilizumab or anakinra and by using different multivariable Cox models adjusted for variables related to poor outcome, for the propensity to be treated with tocilizumab or anakinra and after patient matching. Results: Sixty-six patients who received immunotherapy (49 tocilizumab, 17 anakinra) and 28 patients who did not receive immunotherapy were included. The in-hospital crude mortality was 30,3% in treated patients and 50% in non-treated (OR 0.77, 95% CI 0.56-1.05, p=0.069). The adjusted Cox model showed an association between therapy with immunotherapy and in-hospital mortality (HR 0.40, 95% CI 0.19-0.83, p=0.015). This protective effect was further confirmed in the analysis adjusted for propensity score, in the propensity-matched cohort and in the cohort of patients with invasive mechanical ventilation within 2 hours after ICU admission. Conclusions: Although important limitations, our study showed that cytokine-blocking agents seem to be safe and to improve survival in COVID-19 patients admitted to ICU with ARDS and the need for mechanical ventilation