Pre-existing Damage Research Articles

The effects of pre-existing damage on the safety of main bridge piers in the sea

Bridge piers founded in the sea are at risk of being weakened by cracking, corrosion and erosion. To assess whether the piers of a sea crossing are safe, it is necessary to consider pre-existing damage to the pier and its foundations. In this study, finite-element analysis was used to simulate different degrees of damage from cracking, steel corrosion, concrete corrosion and foundation erosion of a main sea-crossing pier and its piled foundation. The effect of the varying levels of damage on the behaviour of the pier and its foundation under wave action, ship collision and earthquake was then modelled. The research results provide important technical support for assessing the safety of main bridge piers in the sea.

Experimental study of the dynamic indentation damage in thermally shocked granite

This paper presents an experimental procedure to study the effects of pre-existing cracks and damage on the rock behavior under dynamic indentation. To gain better understanding on the mechanism involved in percussive-rotary drilling procedure, a modified Split Hopkinson Pressure Bar device was used to carry out dynamic indentation tests, where rock drill buttons were impacted on rock samples with dimensions of 30 cm × 30 cm × 30 cm. Before the mechanical testing, the samples were thermally shocked using a plasma spray gun for periods of 3, 4, and 6 seconds. The plasma gun produces a powerful heat shocks on the rock sample, and even short exposures can change the surface structure of the samples and provide samples with different crack patterns and surface roughness for experimental testing. The effects of the heat shock damage on the dynamic indentation behavior of the rock were characterized with single- and triple-button indentation tests. The specific destruction work was used to characterize the effects of heat shocks on the material removal during dynamic indentation. The results show that the force-displacement response of the rock does not change much even if the rock surface is severely damaged by the heat shock, however, the destruction work decreases significantly. This means that the same loading removes more volume if the material surface is pre-damaged, and that the efficiency of the indentation process cannot be evaluated from the bit-rock interaction forces alone. The presented experimental framework can be a useful tool for the verification of numerical models where the rock microstructure and especially the microcracks are essential.

Short Axial Length and Iris Damage Are Associated With Iris Posterior Synechiae After Descemet Membrane Endothelial Keratoplasty in Asian Eyes.

To evaluate the frequency and severity of iris posterior synechiae after Descemet membrane endothelial keratoplasty (DMEK) and to investigate possible causes of iris posterior synechiae. Twenty-three eyes were investigated in 20 Asian patients who underwent DMEK 1 month after phacoemulsification and intraocular lens implantation surgery. A preexisting iris damage score was defined by iris damage and classified into 5 grades. Six months after DMEK, the iris posterior synechiae severity score was evaluated based on the extent of posterior synechiae, according to every 45 degrees of the pupillary rim (posterior synechiae score, 0-8). Correlations were analyzed between the posterior synechiae score and preexisting factors (preexisting iris damage score, axial length [AXL], anterior chamber depth, and anterior chamber volume, both before and after cataract surgery). Iris posterior synechiae appeared in 20 of 23 eyes (87.0%). Best spectacle-corrected visual acuity significantly improved at 6 months after DMEK (P < 0.001). Endothelial cell density was 1596 ± 530 cells/mm (P < 0.001); loss of cell density was 37.8 ± 19.9% at 6 months. Single regression analysis showed that the onset of iris posterior synechiae was correlated with the preexisting iris damage score (P = 0.006, r = 0.55), AXL (P < 0.001, r = -0.71), anterior chamber depth (P < 0.001, r = -0.70), and anterior chamber volume before cataract surgery (P < 0.001, r = -0.79). Iris posterior synechiae after DMEK frequently appeared in Asian eyes with shorter AXLs or a damaged iris.

Outcome of haematopoietic stem cell transplantation in dyskeratosis congenita.

Dyskeratosis congenita (DC) is a genetic multisystem disorder with frequent involvement of the bone marrow. Haematopoietic stem cell transplantation (HSCT) is the only definitive cure to restore haematopoiesis, even though it cannot correct other organ dysfunctions. We collected data on the outcome of HSCT in the largest cohort of DC (n=94) patients ever studied. Overall survival (OS) and event-free survival (EFS) at 3years after HSCT were 66% and 62%, respectively. Multivariate analysis showed better outcomes in patients aged less than 20years and in patients transplanted from a matched, rather than a mismatched, donor. OS and EFS curves tended to decline over time. Early lethal events were infections, whereas organ damage and secondary malignancies appeared afterwards, even a decade after HSCT. A non-myeloablative conditioning regimen appeared to be most advisable. Organ impairment present before HSCT seemed to favour the development of chronic graft-versus-host disease and T-B immune deficiency appeared to enhance pulmonary fibrosis. According to the present data, HSCT in DC is indicated in cases of progressive marrow failure, whereas in patients with pre-existing organ damage, this should be carefully evaluated. Further efforts to investigate treatment alternatives to HSCT should be encouraged.

F115. Analyzing intraoperative neuromonitoring of visual evoked potentials parameters to optimize VEP monitoring usefulness

Intraoperative neuromonitoring of visual evoked potentials (IONM VEP) has been considered as unreliable because of its instability and poor association with postoperative functional outcome. The aim of this study is to analyze different IONM VEP parameters to optimize its monitoring usefulness. IONM VEP was carried out for 22 sides (eyes) in 11 surgeries, including one frontal lobe lesion, 9 standard transsphenoidal (TSS), and one extended TSS surgeries at the Lozano Blesa University Hospital. A preoperative neurophysiologic examination was performed to evaluate visual function in all patients. LED goggles stimulation was given with stimulus duration of 15 ms, intensity of 1.5–3 cd/s.m-2 and repetition rate from 0.5 Hz to 3.0 Hz until waveforms were feasible and reproducible. Additional recording scalp electrodes (LO1: 5 cm left of O1 and LO2: 5 cm right of O2) were added to the well-known montage (Oz-Cz/Fz, O1-Cz/Fz, O2-Cz/Fz), as we wanted to assess recording reliability. Once VEP responses were obtained, pupil dilatation was induced with mydriatic agents, (prior ophthalmologic assessment) followed 20 min. later by at least two consecutive VEP recordings, to evaluate VEP N2-P2 component amplitude and latency. Although anesthetic regimen consisted in total intravenous anesthesia (TIVA) in all our cases, after surgical completion and VEP closing traces gathering, halogenated agents were added at ascending doses (from 0.1 CAM to 1.5 CAM), to value VEP waveforms stability. Written informed consent for the surgery and IONM were obtained from all patients. All patients underwent pre-operative examination. In these patients, six had visual disturbances (one was severe). Ten patients were maintained under TIVA, and sevoflurane was used incidentally in one patient. Stable VEP waveforms were obtained in all patients, except in one patient with preexisting damage to the visual pathway, and another one in whom sevoflurane was used for anesthesia. The stimulus frequency showing more stable and higher waveform was below 1 Hz. There was a significant increase in VEP amplitude, but no effect on the latency after the mydriatic drug instilling. VEP traces were recordable in all channels, but in one case in where they were only obtained throughout LO1 and LO2 recording channels. The administration of halogenates agents produced a doses-dependent decrease in VEP amplitude and latency prolongation in five patients, and a complete loss of potential in three patients with doses above 1.1 CAM, all 15–20 min after application. Recording reliable VEPs hinge on both physiological and technical aspects. VEPs may be mitigated in patients with preoperative impaired visual function. Halogenated agents showed a major influence on IONM VEP stability. The use of cycloplegics helped in obtaining larger responses. Choosing the right stimulus frequency and including additional recording electrodes (LO1-LO2), seemed to enhance the reliability of stimulus-recordings parameters.

Long-Term Follow-Up Study of Liver-Related Outcome After Bilio-Pancreatic Diversion in Patients with Initial, Significant Liver Damage.

Obesity is associated with NAFLD, and bariatric surgery has significant impact on this liver disease, with reported improvement in hepatic fibrosis. To investigate the effects of bariatric surgery on long-term liver disease-related outcome in obese patients with nonalcoholic fatty liver disease (NAFLD) and significant liver damage. This study included 56 NAFLD patients who underwent bilio-pancreatic diversion for morbid obesity and who had significant fibrosis at intraoperative liver biopsy. Data were analyzed at 1, 3, and 5years of follow-up, and at the latest available visit in patients who had longer follow-up. We assessed the incidence of clinically relevant liver events (ascites, hepatic encephalopathy, portal hypertension-related bleeding, and jaundice) as well as modifications of a validated biochemical index such as the NAFLD score. During a median follow-up of 78months, median weight decreased from 119 to 78kg (P < 0.0001), and median body mass index decreased from 45.2 to 29.0kg/m2 (P < 0.0001). None of the patients developed clinical complications of liver disease, and none died due to liver-related causes. Median NAFLD score significantly decreased (P = 0.0005) during follow-up from -0.929 (-1.543 to -0.561) to -1.609 (-2.056 to -1.102). The NAFLD score category was unchanged in 32 patients (57%), improved in 18 (32%), and worsened in 6 (11%). Patients with NAFLD and proven histological liver damage at surgery do not develop complications of liver disease in long term after bilio-pancreatic diversion. Moreover, noninvasive parameters of liver damage improve. Thus, preexisting liver damage does not seem to be a contraindication to bilio-pancreatic diversion.

Pinched Cord and Overdriven Staple Failures: Research on the Causation of an Electrical Fire

In the past, some fire investigators have determined the cause of a fire to be electrical in nature based, in part, on the presence of an electrical cord or cable found beneath a furniture leg or a cable wedged tightly under a staple. While fires resulting from these events are possible, the mechanisms that lead to these failures are poorly understood. In this paper, the results of four research projects are presented. The first three projects focused on the creation of a pinched cord failure under various current loads and pressures. In the last project, a typical nonmetallic-sheathed cable was damaged and then installed with an overdriven staple over the damaged location. In all tests, the cords and cables were subjected to current loads varying between 100 and 250% of the rated ampacity. The failure rate of pinched cords was approximately 1%, but required the use of overloaded circuits and pre-existing damage or special orientation of the cord under test. A critical factor worth considering with these failures, which is often not accounted for, is time. These failures may take weeks, months, or years to occur under normal conditions, although some investigators may assume they develop nearly instantaneously. The conditions of the circuit are also important, as the only way a failure developed in these tests was by operating the circuits in excess of their rated parameters.

Synergistically-enhanced ion track formation in pre-damaged strontium titanate by energetic heavy ions

Latent ion tracks created by energetic heavy ions (12 MeV Ti to 946 MeV Au) in single crystal SrTiO3 are investigated using Rutherford backscattering spectrometry and scanning transmission electron microscopy. The results demonstrate that pre-existing irradiation damage, introduced via elastic collision processes, interacts synergistically with the electronic energy deposition from energetic heavy ions to enhance formation of latent ion tracks. The average amorphous cross-section increases with the level of pre-damage and is linearly proportional to the electronic energy loss of the ions, with a slope dependent on the pre-damage level. For the highest energy ions (629 MeV Xe and 946 MeV Au), the tracks are continuous over the pre-damaged depth, but become discontinuous beyond the pre-damaged region. This work provides new understanding and insights on ion-solid interactions that significantly impact the interpretation of latent track formation processes, models of amorphization, and the fabrication of electro-ceramic devices.

Influence of pre-existing damages on the degradation behavior of crystalline silicon photovoltaic modules

In this paper, the influence of pre-existing crystalline damage, such as cracked or broken cells or soldering failures, as they are frequently observed in operating photovoltaic (PV) plants, on the degradation behavior of mono- and polycrystalline silicon PV modules is investigated. In particular, it is analyzed if and to what extent pre-damage introduced prior to lamination propagates upon stress exposure. Therefore, the pre-damaged modules are exposed to various accelerated aging conditions in order to analyze the impact of the pre-damage on the degradation behavior under the respective aging scenario. In order to separate the influence of the pre-damage from composition-induced influences, the choice of materials used in the modules is varied. These investigations reveal that none of the accelerated aging tests causes any change in the pre-existing damage. In fact, the degradation behavior and rate rather depended on the choice of the module components than on the nature of the pre-damage. Finally, these results are compared with indoor and outdoor results obtained from other studies.

The Burden of Diabetes and the Chance of a Previous Stroke: Thrombolysis for Recurrent Stroke in Diabetics

Intravenous thrombolysis with recombinant tissue plasminogen activator is still not approved by the European Medicines Agency for patients with diabetes mellitus and previous stroke. We assessed functional benefit and potential risk of thrombolysis in patients with diabetes and previous stroke and the influence of age, preexisting diabetic damage, as well as acute and chronic hyperglycemia on outcome, symptomatic intracranial hemorrhage, and in-hospital mortality. We analyzed 527 consecutive patients treated with thrombolysis for acute stroke. Poor outcome was defined as deterioration of prestroke modified Rankin Scale (mRS) to 3 or greater at discharge. Symptomatic intracranial hemorrhage was defined according to the Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria. Of the patients, 35.9% were diabetic and 33.2% had previous stroke. Of these patients, 14.4% were diabetics with previous stroke (index group). The rate of patients with poor functional outcome at discharge, symptomatic intracranial hemorrhage, or mortality did not differ between the index group and patients with either diabetes or previous stroke in 2 × 2 comparisons. Diabetics with first-ever stroke showed significantly more symptomatic intracranial hemorrhage (9.7%, P < .001) than the other groups, poorer functional recovery (P = .036), and the highest rate of mortality (12.4%, P < .001). Significant predictors for poor outcome were age (P < .001) and HbA1c (P = .013), for symptomatic intracranial hemorrhage HbA1c (P = .006) and for mortality acute hyperglycemia (P = .001) and age (P = .004). Diabetics with previous stroke should not be withheld from intravenous thrombolysis. The risk of complications derives primarily from poor long-term metabolic control rather than from acute hyperglycemia or from previous stroke.

Bearing capacity of concrete hinges subjected to eccentric compression: multiscale structural analysis of experiments

Existing design guidelines for concrete hinges are focusing on serviceability limit states. Lack of knowledge about ultimate limit states was the motivation for this work. Experimental data are taken from a testing series on reinforced concrete hinges subjected to eccentric compression up to their bearing capacity. These tests are simulated using the finite element (FE) software Atena science and a material model for concrete implemented therein. The first simulation is based on default input derived from measured values of Young’s modulus and of the cube compressive strength of the concrete. The numerical results overestimate the initial stiffness and the bearing capacity of the tested concrete hinges. Therefore, it is concluded that concrete was damaged already before the tests. A multiscale model for tensile failure of concrete is used to correlate the preexisting damage to corresponding values of Young’s modulus, the tensile strength, and the fracture energy of concrete. This allows for identifying the preexisting damage in the context of correlated structural sensitivity analyses, such that the simulated initial stiffness agrees well with experimental data. In order to simulate the bearing capacity adequately, the triaxial compressive strength of concrete is reduced to a level that is consistent with regulations according to Eurocode 2. Corresponding FE simulations suggest that the ductile structural failure of concrete hinges results from the ductile material failure of concrete at the surface of the compressed lateral notch. Finally, Eurocode-inspired interaction envelopes for concrete hinges subjected to compression and bending are derived. They agree well with the experimental data.

Crystallographic orientation-dependent growth mode of microstructurally fatigue small crack in a laminated Ti–6Al–4V alloy

The fatigue life of Ti–6Al–4V alloy exhibits significant scatter, which is derived from the statistical scatter of uncontrollable material factors. In particular, crack propagation behaviors in microstructurally small cracks strongly depend on material factors. It is necessary to understand the mechanisms underlying the scatter of fatigue properties. In this study, the dominant material/mechanical factors of microstructurally small fatigue crack growth behaviors are extracted, and the mechanisms of fatigue crack propagation life scatter derived from them are clarified. A Ti–6Al–4V billet was studied in which the microstructure was fully laminated with α and β phases. The major constituent phase was α. Microstructurally small artificial defects were introduced at a center of prior β grains by a focused ion beam (FIB). A fatigue test was carried out at a stress ratio R = 0, stress amplitude σa = 400 MPa, and frequency 1.3 × 10-2 Hz in a vacuum using scanning electron microscopy (SEM). In situ SEM observation was carried out around each FIB notch. After the fatigue test, the dependence of the crack growth path on crystallographic orientation was investigated by using electron backscattered diffraction. It was found that microstructurally small crack growth behaviors depended on crystallographic orientation. The dominant crack growth mechanism was the mode II crack growth mechanism by shear stress along the basal plane as a driving force. The dominant factor that causes large scatter of fatigue life in a α- Ti–6Al–4V alloy is the difference in resolved shear stress along the basal plane. Specifically, the difference in the angle between the basal plane and loading direction, the low reproducibility of the mode II crack growth mechanism, and the random position of pre-existing damage cause the scatter of fatigue crack growth rate.

Cascade debris overlap mechanism of 〈100〉 dislocation loop formation in Fe and FeCr

Two types of dislocation loops are observed in irradiated α-Fe, the 1/2〈111〉 loop and the 〈100〉 loop. Atomistic simulations consistently predict that only the energetically more favourable 1/2〈111〉 loops are formed directly in cascades, leaving the formation mechanism of 〈100〉 loops an unsolved question. We show how 〈100〉 loops can be formed when cascades overlap with random pre-existing primary radiation damage in Fe and FeCr. This indicates that there are no specific constraints involved in the formation of 〈100〉 loops, and can explain their common occurrence.

Phase I dose-escalation study of pazopanib combined with bevacizumab in patients with metastatic renal cell carcinoma or other advanced tumors

BackgroundVascular endothelial growth factor (VEGF) directed therapies are being used in a large number of advanced tumors. Metastatic renal cell carcinoma (mRCC) is highly dependent on the VEGF pathway; VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKI) and humanized VEGF monoclonal antibody have been registered for clinical use in advanced renal cell carcinoma. The VEGFR TKI, pazopanib, with a rather manageable toxicity profile, was preferred to sunitinib by mRCC patients. We investigate the combination of pazopanib and bevacizumab to determine the maximum tolerated dose (MTD) in mRCC and other advanced solid tumors.MethodsIn this bicentric phase I trial with a 3 + 3 + 3 dose-escalation design, patients received oral pazopanib once daily plus intravenous infusion of bevacizumab every 2 weeks from D15, at one of the four dose levels (DL) planned according to the occurrence of dose limiting toxicities (DLT). 400 and 600 mg pazopanib were respectively combined with 7.5 mg/kg bevacizumab in DL1 and DL2, and 600 and 800 mg pazopanib with 10 mg/kg bevacizumab in DL3 and DL4. Tumor response was evaluated every 8 weeks. Blood samples were assayed to investigate pazopanib pharmacokinetics.ResultsTwenty five patients including seven mRCC were enrolled. Nine patients received the DL1, ten received the DL2. No DLT were observed at DL1, five DLT at DL2, and 3 DLT in the six additional patients who received the DL1. A grade 3 microangiopathic hemolytic anemia syndrome was observed in four (16%) patients. Five (22%) patients achieved a partial response. The mean (range) plasmatic concentrations of 400 and 600 pazopanib were respectively 283 (139–427) and 494 (227–761) μg.h/mL at Day 1, and 738 (487–989) and 1071 (678–1464) μg.h/mL at Day 15 i.e. higher than those previously reported with pazopanib, and were not directly influenced by bevacizumab infusion.ConclusionsThe combination of pazopanib and bevacizumab induces angiogenic toxicity in patients without any pre-existing renal or vascular damage. Even if a marginal efficacy was reported with five (22%) patients in partial response in different tumor types, the toxicity profile compromises the development of this combination.Trial registrationThe study was retrospectively registered on ClinicalTrials.gov (number NCT01202032) on 2010, Sept 14th.

Role of atomic-level defects and electronic energy loss on amorphization in LiNbO3 single crystals

Understanding complex non-equilibrium defect processes, where multiple irradiation mechanisms may take place simultaneously, is a long standing subject in material science. The separate and combined effects of elastic and inelastic energy loss are a very complicated and challenging topic. In this work, LiNbO3 has been irradiated with 0.9 MeV Si+ and 8 MeV O3+, which are representative of regimes where nuclear (Sn) and electronic (Se) energy loss are dominant, respectively. The evolution of damage has been investigated by Rutherford backscattering spectrometry (RBS) in channeling configuration. Pristine samples were irradiated with 0.9 MeV Si+ ions to create different pre-existing damage states. Below the threshold (Se,th = 5–6 keV nm−1) for amorphous track formation in this material, irradiation of the pristine samples with a highly ionizing beam of 8 MeV O3+ ions, with nearly constant Se of about 3 keV nm−1, induces a crystalline to amorphous phase transition at high ion fluences. In the pre-damaged samples, the electronic energy loss from the 8 MeV O3+ ions interacts synergistically with the pre-existing damage, resulting in a rapid, non-linear increase in damage production. There is a significant reduction in the incubation fluence for rapid amorphization with the increasing amount of pre-existing damage. These results highlight the important role of atomic-level defects on increasing the sensitivity of some oxides to amorphization induced by electronic energy loss. Controlling the nature and amount of pre-damage may provide a new approach to tuning optical properties for photonic device applications.

Analysis of the plastic zone under mixed mode fracture in bonded composite repair of aircraft structures

Material fracture by opening (mode I) is not the only failure criteria responsible for fracture propagation. Many industrial examples show the presence of mode II and mixed mode I + II. In the present work, numerical analyses of the three-dimensional and non-linear finite element method are used to estimate the performance of the bonded composite repair of metallic aircraft structures with a pre-existent damage by analyzing the plastic zone size ahead of repaired cracks under mixed mode loading, to assess the effect of the composite repair system on the plastic zone. The Von Mises stress is used to predict yielding of materials under this loading condition. The extension of the plastic zone, which takes place at the tip of a crack, strictly depends on many variables, such as the yield stress of the material, the loading conditions, the crack size and the thickness of the cracked component.The obtained results have demonstrated that the plastic zone ahead of the crack is significantly reduced by the presence of composite patch materials. Furthermore, parametric analysis has been carried out to evaluate the effect of lay-up and material system variation on the J integral.

Does pregnancy have any impact on long term damage accrual and on the outcome of lupus nephritis?

No data are available about the impact of pregnancy on the long-term outcome of lupus nephritis.Thirty-two women with lupus nephritis with a 10-year follow-up after their first pregnancy (“women who gave birth”) and 64 matched controls with the same follow-up and who never had pregnancies (“controls”) were compared for the occurrence of SLE flares, chronic kidney disease (CKD), and SLICC/ACR Damage Index (SDI) in the post pregnancy period. The same evaluations were done before and after pregnancy in women who gave birth. The predictors of CKD and damage accrual in the whole population were studied.All patients were Caucasians and had biopsy proven LN. At conception and after 10 years, in both groups, less than 10% of patients had active renal disease (p = ns). Controls had more frequent arterial hypertension (p = 0.025). Between the two groups there was no difference in SLE flares and in CKD free survival curves (p = 0.6 and p = 0.37) during the 10-year follow-up. In both groups, the temporal trend, based on annual evaluation, of glomerular filtration rate and serum creatinine shows a significant decrease and increase respectively. However, the women who gave birth persistently maintained better values of renal function than controls during the whole follow-up (P = 0.00001). There was no difference in the CKD-free survival curves. SDI did not increase significantly in women who gave birth in comparison to controls. All the above mentioned clinical parameters were comparable before and after pregnancy in the women who gave birth.Among the basal clinical characteristics, high serum creatinine and occurrence of SLE flares predicted CKD, whereas low levels of C3, pre-existing damage score, and occurrence of SLE flares predicted SDI increase. Pregnancy was not a predictor of CKD or SDI increase.Carrying a pregnancy during inactive lupus nephritis does not seem to increase the rate of SLE flares, worsen renal prognosis or increase SDI significantly in the very long-term.

The VEGF-A inhibitor sFLT-1 improves renal function by reducing endothelial activation and inflammation in a mouse model of type 1 diabetes

Aims/hypothesisAnimal models of diabetic nephropathy show increased levels of glomerular vascular endothelial growth factor (VEGF)-A, and several studies have shown that inhibiting VEGF-A in animal models of diabetes can prevent albuminuria and glomerular hypertrophy. However, in those studies, treatment was initiated before the onset of kidney damage. Therefore, the aim of this study was to investigate whether transfecting mice with the VEGF-A inhibitor sFlt-1 (encoding soluble fms-related tyrosine kinase 1) can reverse pre-existing kidney damage in a mouse model of type 1 diabetes. In addition, we investigated whether transfection with sFlt-1 can reduce endothelial activation and inflammation in these mice.MethodsSubgroups of untreated 8-week-old female C57BL/6J control (n = 5) and diabetic mice (n = 7) were euthanised 5 weeks after the start of the experiment in order to determine the degree of kidney damage prior to treatment with sFLT-1. Diabetes was induced with three i.p. injections of streptozotocin (75 mg/kg) administered at 2 day intervals. Diabetic nephropathy was then investigated in diabetic mice transfected with sFlt-1 (n = 6); non-diabetic, non-transfected control mice (n = 5); non-diabetic control mice transfected with sFlt-1(n = 10); and non-transfected diabetic mice (n = 6). These mice were euthanised at the end of week 15. Transfection with sFlt-1 was performed in week 6.ResultsWe found that transfection with sFlt-1 significantly reduced kidney damage by normalising albuminuria, glomerular hypertrophy and mesangial matrix content (i.e. glomerular collagen type IV protein levels) (p < 0.001). We also found that transfection with sFlt-1 reduced endothelial activation (p < 0.001), glomerular macrophage infiltration (p < 0.001) and glomerular TNF-α protein levels (p < 0.001). Finally, sFLT-1 decreased VEGF-A-induced endothelial activation in vitro (p < 0.001).Conclusions/interpretationThese results suggest that sFLT-1 might be beneficial in treating diabetic nephropathy by inhibiting VEGF-A, thereby reducing endothelial activation and glomerular inflammation, and ultimately reversing kidney damage.

Acute kidney injury in head and neck cancer patients treated with chemoradiation with cisplatin: A single-center cohort study.

e17559 Background: Patients with advanced head and neck cancer (HNC) are commonly treated with chemoradiation with concomitant cisplatin. Acute kidney injury (AKI) is considered a dose-limiting toxicity of cisplatin. We aim to describe the incidence and risk factors of AKI. Methods: In our tertiary center, we retrospectively identified 261 patients with advanced HNC and adequate renal function who were treated curatively from 2008 to 2015 using radiotherapy and concurrent three-weekly cisplatin. Outcome was the first AKI episode, defined according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines as a ≥50% rise in serum creatinine compared to baseline. Several potential predictors were investigated by means of logistic regression analyses. Results: In our cohort (mean age 58 ± 8 years, 74.3% male), a total of 102 (39.1%) patients developed AKI. Factors significantly associated with AKI in the univariate analysis were: age, alcohol consumption, excessive smoking, diabetes, hypertension, diuretic use, renin-angiotensin-aldosterone-system blockers, and administration of furosemide when indicated during first cisplatin cycle. In the multivariable model smoking 6-25 and &gt; 25 cigarettes per day (OR 1.85; 95% CI 1.01-3.39 and OR 3.22; 95% CI 1.34-7.70, respectively), diabetes (OR 2.58; 95% CI, 1.01-6.61), furosemide (OR 2.39; 95% CI, 1.36-4.18) , and hypertension (OR 2.79; 95% CI, 1.52-5.12) remained independent risk factors for AKI. Conclusions: The identified risk factors smoking, diabetes, and hypertension may have caused pre-existing kidney damage and therefore have predisposed to AKI. Co-administration of furosemide with cisplatin is a potentially reversible risk factor for AKI.

Constitutive modelling of the strain-rate dependency of fabric reinforced polymers

Among the various mechanisms which occur during impact, the strain rate effect plays a significant role on the mechanical response of layered carbon fibre reinforced polymer structure. In this work, the viscoelastic behaviour of the material is studied to introduce a strain-rate dependency. To preserve numerical efficiency the generalised Maxwell model, formulated in the strain-space, is taken as a basis. The non-linear viscoelastic behaviour is introduced by coupling the generalised Maxwell model with a pre-existing intralaminar matrix continuum damage model. The fact that the Maxwell model preserves the explicit scheme of the damage model leads to an efficient material model for impact simulations. This paper proposes a complete framework to implement the strain-rate sensitive damage model in an explicit finite element code (for low-speed impact simulations). For this purpose, the procedure of parameter identification, based on DynamicMechanical Analysis, is given. Furthermore, a challenging experimental procedure on high-speed jack device with a particular attention paid to the consistency of the results is proposed to validate the developed model.