Long-term Loss Research Articles

PULM4: Silicone-Based Hollow Fiber Membrane Lungs For Long-Term Extracorporeal Respiratory Supports: Initial Results From A Pilot Study Using A Goat Model

Background: There has been an increasing demand of organs for lung transplant to save those who suffer from end-stage lung disease. However, the number of organ donations have never matched that of candidate recipients, leading to a high mortality rate on the waiting period for transplant. One potential approach to decrease the wait-list mortality is to develop an artificial gas-exchange device that can support lung function until the time of transplantation. We’ve started to develop a gas-exchange system that consists of silicone-based membrane lungs with methacryloyloxyethyl phosphorylcholine (MPC) polymer coating and tubing system for a longer-term use. Objective: The purpose of this study was to evaluate the long-term durability, oxygenation, and pressure loss of newly developed artificial lungs using a large animal model. Materials and methods: The surface area of the membrane lung is approximately 2 m2. Central ECMO from the pulmonary artery to the left atrium was introduced to a healthy female goat via left thoracotomy under general anesthesia (N=3). Unfractionated heparin infusion was utilized for anticoagulation (target activating clotting time: 150-200 sec). After recovery from the surgery, blood gas and flow pressure before and after the artificial lung with flow rates of 1, 2, and 3 L/min were tested weekly. Daily physiological data, regular blood biochemistry and coagulation tests, and histopathological findings after autopsy were also evaluated. Thrombus adhesion to the silicone membrane was evaluated using an electron microscopy after the experiments. Results: Durations for testing the artificial lungs were 53, 58, and 100 days. The experiments were terminated due to an accidental tubing event, a sudden cardiac complication, and massive renal hemorrhage. Averages of oxygen transfer rates (ml/min) and oxygen pressure gradients (mmHg) at each flow rate were 63.3 and 466.5 at 1 L/min, 118.3 and 291.3 at 2 L/min, and 152.7 and 138.2 at 3 L/min. Averages of flow pressures through the artificial lungs at each flow rate were 21.7 mmHg at 1 L/min, 44.7 at 2 L/min, and 66.9 at 3 L/min. No significant increase of pressure loss or decrease of oxygenation was observed throughout the experimental periods. Thrombus at the inlet of the membrane was mainly observed, but those inside and near the outlet were minor, indicating the long-term antithrombotic property of the polymer coating. Electron microscopical examinations revealed minimal thrombus formation on the hollow fiber membrane inside the lung. At autopsy, although micro-infarction and thrombus were observed in the heart and kidney, native lungs were well maintained without appreciable congestion. Conclusion: The newly developed MPC polymer-coated silicone-based lungs could be used stably for more than 50 days. Improving the oxygenation in higher blood flow rates with reduced pressure loss is our ongoing subject to work on.

Low-Carbon Emission Demolition of an Existing Urban Bridge Based on SPMT Technology and Full Procedure Monitoring

Due to the need for comprehensive transportation hub construction, an existing bridge in a bustling urban area with an operation duration of 25 years was required to be demolished. Based on Life Cycle Assessment (LCA), this paper proposes a scheme of "Self-propelled modular transporter (SPMT) technology + large segment cutting" to compare the carbon emissions of demolition schemes qualitatively and quantitatively. To ensure structural safety during demolition, the finite element analysis was used to simulate the entire demolishing process, and measuring points were set up to monitor the deformation of the main girder in real time under various demolition conditions. The results indicate that the scheme of SPMT has the lowest carbon emissions during the demolition stage. Additionally, the long-term prestress loss shall be considered when demolishing existing bridges; the suggested 25% proportional value for the long-term prestress loss of the Caitian Bridge is appropriate, which is determined by comparing the calculated results from various formulas. The values of the calculated and measured deformations of the main girder under different working conditions are in good agreement, with errors mostly within 10% and a maximum of no more than 14.7%. The demolition of the entire bridge was completed in a total of 28 h with little noise and pollution, and the impact on daily traffic was avoided, proving that the proposed “SPMT technology + large segment cutting” scheme is safe, efficient, and achieves the goal of green, environmentally friendly, and rapid demolition.

A Highly Stable Fusion Positioning System of Smartphone under NLoS Acoustic Indoor Environment

Fusion positioning technology requires stable and effective positioning data, but this is often challenging to achieve in complex Non-Line-of-Sight (NLoS) environments. This paper proposes a fusion positioning method that can achieve stable and no hop points by adjusting parameters and predicting trends, even with a one-sided lack of fusion data. The method combines acoustic signal and Inertial Measurement Unit (IMU) data, exploiting their respective advantages. The fusion is achieved using the Kalman filter and Bayesian parameter estimation is performed for tuning IMU parameters and predicting motion trends. The proposed method overcomes the problem of fusion failure caused by long-term unilateral data loss in traditional fusion positioning. The positioning trajectory and error distribution analysis show that the proposed method performs optimally in severe NLoS experiments.

Reconfigurable Low-Power TiO2 Memristor for Integration of Artificial Synapse and Nociceptor

Bio-mimetic advanced electronic systems are emerging rapidly, engrossing their applications in neuromorphic computing, humanoid robotics, tactile sensors, and so forth. The biological synaptic and nociceptive functions are governed by intricate neurotransmitter dynamics that involve both short-term and long-term plasticity. To emulate the neuronal dynamics in an electronic device, an Ag/TiO2/Pt/SiO2/Si memristor is fabricated, exhibiting compliance current controlled reversible transition of volatile switching (VS) and non-volatile switching (NVS). The origin of the VS and NVS depends on the diameter of the conducting filament, which is explained using a field-induced nucleation theory and validated by temporal current response measurements. The switching delay of the device is used to determine the characteristic nociceptive behaviors such as threshold, relaxation, inadaptation, allodynia, and hyperalgesia. The short-term and long-term retention loss attributed to the VS and NVS, respectively, is used to emulate short-term memory and long-term memory of the biological brain in a single device. More importantly, synergistically modulating the VS-NVS transition, the complex spike rate-dependent (SRDP) and spike time-dependent plasticity (STDP) with a weight change of up to 600% is demonstrated in the same device, which is the highest reported so far for TiO2 memristors. Furthermore, the device exhibits very low power consumption, ∼3.76 pJ/spike, and can imitate synaptic and nociceptive functions. The consolidation of complex nociceptive and synaptic behavior in a single memristor facilitates low-power integration of scalable intelligent sensors and neuromorphic devices.

Deep learning-based reconstruction of missing long-term girder-end displacement data for suspension bridge health monitoring

The flexibility of a suspension bridge usually results in significant longitudinal displacement at the end of the main girder under the joint action of environmental factors and traffic loads. Fluctuation amplitude and accumulation of girder-end displacement (GED) are primary data for the performance evaluation of suspension bridge elements, including expansion joints, supports, and dampers. However, the performance of the bridge structural health monitoring (SHM) system is frequently deteriorated by the long-term continuous GED data loss or anomaly. In this study, this issue of the suspension bridge SHM system was resolved by proposing a deep learning-based framework for reconstructing the missing GED data. Under this framework, a long short-term memory (LSTM) network-based regression model was first built between the ambient temperature data and the thermal-induced low-frequency components of GED data. Next, a U-net-based spectral bandwidth expansion model was applied for the step-by-step generation of vehicle/wind-induced high-frequency GED data terms based on the available low-frequency ones. Finally, a statistical correction strategy was employed to improve the prediction accuracy for the high-frequency GED data fluctuation amplitudes. The trained model for the reconstruction of the missing GED data uses only the air temperature input values in the data loss period. This method is especially lucrative when GED data in all sensor channels are missing. The reliability and efficiency of the proposed model were demonstrated by a case study. Specifically, the problem of reconstructing the missing GED data in the SHM system of the Jiangyin Yangtze River Bridge in China was considered. Using the relative error of cumulative GED as the performance indicator, a reconstruction precision within 10% was obtained.

Comparison of Long-Term Outcomes of DSEK and DMEK in Fuchs Endothelial Dystrophy.

This study aimed to compare the long-term endothelial cell loss, graft survival, and clinical outcomes in patients with Fuchs endothelial dystrophy (FED) after Descemet stripping endothelial keratoplasty (DSEK) and Descemet membrane endothelial keratoplasty (DMEK) using a standardized surgical protocol. Three hundred and six consecutive DSEK and DMEK grafts of 223 patients with FED performed by 8 surgeons between January 2006 and August 2022 were analyzed. The primary outcome measures were graft survival, endothelial cell loss, and best spectacle-corrected visual acuity. At 5 years, graft survival was 96% for both DSEK and DMEK eyes. The mean percentage of endothelial cell loss was 57.7 ± 17.1 in DSEK and 56.8 ± 15.2 in DMEK eyes ( P = 0.430). The mean best spectacle-corrected visual acuity was 0.13 ± 0.14 logMAR in DSEK and 0.01 ± 0.18 logMAR in DMEK grafts ( P <0.00001) at 5 years postoperatively. Rebubbling was performed in 7.8% DSEK and 2.1% DMEK grafts ( P = 0.441). Cox regression identified rejection episodes (HR 6.5; 95% CI: 1.70-24.8; P = 0.0062) as a significant contributing factor for graft failure. DMEK had superior visual acuity outcomes compared with DSEK in these patients up to 5 years after surgery. At 5 years, there was no significant difference in graft survival or endothelial cell loss between DSEK and DMEK eyes with FED. We propose that our standardized technique reduces the need for rebubbling.

The Costs of Job Displacement over the Business Cycle and Its Sources: Evidence from Germany

We document the sources behind the costs of job loss over the business cycle using administrative data from Germany. Losses in annual earnings after displacement are large, persistent, and highly cyclical, nearly doubling in size during downturns. A large part of the long-term earnings losses and their cyclicality is driven by declines in wages. Key to these long-lasting wage declines and their cyclicality are changes in employer characteristics, as displaced workers switch to lower-paying firms. These losses increase with duration of nonemployment. Changes in characteristics of displaced workers or displacing firms, and other post-job loss career outcomes explain little of the cyclicality. (JEL E24, E32, J31, J63, J64, J65)

Evolution of kidney allograft loss causes over 40 years (1979–2019)

IntroductionThe improvement of kidney allograft recipient and graft survival showed a decrease over the last 40 years. Long-term graft loss rate remained stable during a 25-year time span. Knowing the changing causes and the risk factors associated with graft loss requires special attention.The present study aimed to assess the causes of graft loss and kidney allograft recipient death. Also, we aimed to compare two different periods (1979−1999 and 2000−2019) to identify changes in the characteristics of the failed allografts and recipient and donors profile. Methods and patientsWe performed a single-center cohort study. We included all the kidney transplant recipients at the Hospital del Mar (Barcelona) between May 1979 and December 2019. Graft loss was defined as recipient death with functioning graft and as loss of graft function (return to dialysis or retransplantation). We assessed the causes of graft loss using clinical and histological information. We also analyzed the results of the two different transplant periods (1979−1999 and 2000−2019). ResultsBetween 1979 and 2019, 1522 transplants were performed. The median follow-up time was 56 (IQR 8–123) months. During follow-up, 722 (47.5%) grafts were lost: 483 (66.9%) due to graft failure and 239 (33.1%) due to death with functioning graft. The main causes of death were cardiovascular (25.1%), neoplasms (25.1%), and infectious diseases (21.8%). These causes were stable between the two periods of time. Only the unknown cause of death has decreased in the last period.The main cause of graft failure (loss of graft function) was the allograft chronic dysfunction (75%). When histologic information was available, antibody-mediated rejection (ABMR) and interstitial fibrosis/tubular atrophy (IF/TA) were the most frequent specific causes (15.9% and 12.6%). Of the graft failures, 213 (29.5%) were early (<1 year of transplantation). Vascular thrombosis was the main cause of early graft failure in the second period (2000−2019) (46.7%) and T-cell-mediated rejection (TCMR) was the main cause (31.3%) in the first period (1979−1999). The causes of late graft loss were similar between the two periods. ConclusionsThe causes of kidney allograft recipient death are still due to cardiovascular and malignant diseases. Vascular thrombosis has emerged as a frequent cause of early graft loss in the most recent years. The evaluation of the causes of graft loss is necessary to improve kidney transplantation outcomes.

Neuroprotective effects of PRG on Aβ25-35-induced cytotoxicity through activation of the ERK1/2 signaling pathway

Ethnopharmacological relevancePhylloporia ribis (Schumach:Fr.)Ryvarden is a genus of needle Phellinus medicinal fungi, parasitic on the living rhizomes of hawthorn and pear trees. As a traditional Chinese medicine, Phylloporia ribis was used in folklore for long-term illness, weakness and memory loss in old age. Previous studies have shown that polysaccharides from Phylloporia ribis (PRG) significantly promoted synaptic growth in PC12 cells in a dose-dependent manner, exhibiting “NGF”-like neurotrophic activity. Aβ25-35 damage to PC12 cells produced neurotoxicity and decreased cell survival, and PRG reduced the apoptosis rate, suggesting that PRG has neuroprotective effects. The studies confirmed that PRG had the potential to be a neuroprotective agent, but its neuroprotective mechanism remained unclear. Aim of the studyWe aimed to elucidate the neuroprotective effects of PRG in an Aβ25-35-induced Alzheimer's disease (AD) model. Materials and methodsHighly-differentiated PC12 cells were treated with Aβ25-35 (AD model) and PRG, and were assessed for cellular apoptosis, inflammatory factors, oxidative stress, and kinase phosphorylation. ResultsThe results showed that the PRG groups effectively inhibited the neurotoxicity, mainly manifested by inhibiting mitochondrial oxidative stress, attenuating neuroinflammatory responses, and improving mitochondrial energy metabolism, eventually resulting in higher cell survival. The expression of p-ERK, p-CREB and BDNF proteins was increased in the PRG groups compared to the model group, which confirmed that PRG reversed the inhibition of the ERK pathway. ConclusionWe provide evidence for neuroprotection conferred by PRG and its mechanism by inhibiting ERK1/2 hyper-phosphorylation, prevention of mitochondrial stress, and subsequent prevention of apoptosis. The study highlights PRG as a promising candidate with neuroprotective effects, the potential of which can be harnessed for identifying novel therapeutic targets.

Exploiting synergistic effect of CO/NO gases for soft tissue transplantation using a hydrogel patch

Autologous skin flap transplantation is a common method for repairing complex soft tissue defects caused by cancer, trauma, and congenital malformations. Limited blood supply range and post-transplantation ischemia-reperfusion injury can lead to distal necrosis of the flap and long-term functional loss, which severely restricts the decision-making regarding the optimal surgical plan. To address this issue, we develop a hydrogel patch that releases carbon monoxide and nitric oxide gases on demand, to afford a timely blood supply for skin flap transplantation during surgery. Using an ischemia-reperfusion dorsal skin flap model in rats, we show that the hydrogel patch maintains the immediate opening of blood flow channels in transplanted tissue and effective blood perfusion throughout the perioperative period, activating perfusion of the hemodynamic donor site. We demonstrate that the hydrogel patch promotes distal vascularization and long-term functional reconstruction of transplanted tissues by inhibiting inflammatory damage and accelerating blood vessel formation.

Melatonin improves skin barrier damage caused by sleep restriction through gut microbiota.

It is widely known that lack of sleep damages the skin. Therefore, it is necessary to explore the relationship between sleep deprivation and skin damage and to find effective treatments. We established a 28-day sleep restriction (SR) mice model simulating continuous long-term sleep loss. We found that SR would damage the barrier function of mice's skin, cause oxidative stress damage to the skin, weaken the oscillations of the skin's biological clock, and make the circadian rhythm of Bacteroides disappear. The circadian rhythm of short-chain fatty acids (SCFA) receptors in the skin was disordered. After melatonin supplementation, the skin damage caused by SR was improved, the oscillations of the biological clock were enhanced, the circadian rhythm of Bacteroides was restored, and the rhythm of the receptor GPR43 of propionic acid was restored. We speculated that the improving effect of melatonin may be mediated by propionic acid produced by the gut microbiota. We verified in vitro that propionic acid could improve the keratinocytes barrier function of oxidative damage. We then consumed the gut microbiota of mice through antibiotics and found that oral melatonin could not improve skin damage. Moreover, supplementing mice with propionic acid could improve skin damage. Our research showed that lack of sleep impaired skin barrier function. Oral melatonin could improve skin damage by restoring the circadian rhythm of Bacteroides and its propionic acid metabolite.

A cost analysis of orthodontic space closure and implant treatment in patients missing maxillary lateral incisors with a long-term perspective.

Few studies within orthodontics present both economic and clinical findings. Missing maxillary lateral incisors is a frequently occurring anomaly. The treatment alternatives most used are orthodontic space closure and prosthetic replacement of the missing tooth. Our aim is to compare the total societal costs of orthodontic space closure (SC) and implant therapy (IT) in patients missing maxillary lateral incisors. Records of 32 patients treated with SC (n = 18) or IT (n = 14) due to missing maxillary lateral incisors were retrieved from the archives. Direct costs and indirect costs in the short- and long-term were analysed using a cost analysis with a societal perspective up of to 12 years post-treatment. Comparing cases treated with SC and IT, the difference in direct short-term costs for treatment is €735.54, whereas SC is the least costly. There is no difference between SC and IT in short-term parent loss of productivity, long-term loss of productivity, costs for transportation, or direct long-term costs. A difference was found between SC and IT-in favour of SC-when comparing patients' loss of productivity (P = 0.007), short-term societal costs (P < 0.001), long-term societal costs (P = 0.037), and total societal costs (P < 0.001). There is a limited number of patient records. Local factors such as subsidies, urban versus rural areas, taxes, etc. can influence monetary variables, so the transferability to other settings may be limited. Patients treated with SC have a lower total societal cost compared to patients treated with IT. There was a difference in productivity loss for patients between SC and IT; however, concerning other indirect parameters and direct long-term costs, there was no difference between the two treatments.

Exploring the therapeutic efficacy of Chlorella pyrenoidosa peptides in ameliorating Alzheimer's disease

Alzheimer's disease (AD) is one of the neurodegenerative disorders, the hallmarks of which include deposits of extracellular beta-amyloid (Aβ) as well as intracellular tau neurofibrillary tangles (NFTs) tangles. With disease progression, neuronal apoptosis combined with cerebral atrophy occurs, leading to cognitive impairment and long-term memory loss. Recently, Chlorella species have been identified as a functional food and are being explored for the prevention of various diseases widely studied to prevent or treat many neurodegenerative diseases. Hence, we for the first time investigated the neuroprotective effects of Chlorella pyrenoidosa short-chain peptides (CPPs) i.e. <1 kDa, 1–3 kDa, 3–10 kDa, and >10 kDa on the in vitro and in vivo neuronal injury models. Our in vitro results showed that CPP with a molecular weight of 1–3 kDa and 3–10 kDa could elevate the survival rate of Aβ1-42 or l-Glutamic acid-injured N2A cells. These treatments also inhibited Aβ and tau NFTs in N2A cells and prevented progressive neuronal cellular damage by suppressing inflammatory cytokines such as PGE2, iNOS, IL-6, TNF-α, COX-2, IL-1β, TGF-β1, and NF-κB. Further, our in vivo Aβ1-42-induced AD mice model demonstrated that 1–3 kDa or 3–10 kDa CPP could improve spatial cognition and learning memory. We also observed a decreased cell loss ratio in CA1-CA3 hippocampal regions. Taken together, our findings imply that CPPs may exert their anti-AD impact through anti-inflammatory, and anti-amyloid activities via reducing APP and tau NFT.

The role of oak species in long-term soil P loss in a humid river bottomland

There is a gap in our understanding of if and how bottomland forest type will affect long-term nutrient cycling and loss. This study aims to determine how different forests affect soil hydrologic variability and whole-soil P loss in a humid-subtropical setting. We used replicate-sampling and measured soil physical, chemical, and mineralogical properties at 12 sites in two forest ecosystems, post oak (Quercus stellata) and cherry bark oak (Quercus pagoda) in Clarks River National Wildlife Refuge in Western Kentucky. We hypothesize that wetting–drying events in redox soils of forested bottomlands can cause positive feedback in whole-soil P loss. Trees with greater P demand (e.g., post oak) take up more water creating more frequent and pronounced episodes in swelling and shrinking of expandable clays. Repeated swelling and shrinking of clays occlude the surface of Fe-Mn oxides from further adsorption of P in acidic soil. This can lead to greater loss or plant uptake of available P. Our results show (i) a significant difference in mean whole-soil P loss between the oak species with more loss in soils underlying the post oak forest, and (ii) a difference in the total P found in the sap- and heartwood of the two oak species. Soil analysis reveals that the clay mineralogy of the post and cherry bark oak sites are similar, and thus, may only play a minor role in governing the whole-soil P loss difference. However, the leaf data analysis suggests that the post oak site could be P and nitrogen-limited, while the cherry bark is only nitrogen limited. Our study shows that differences in the oak forest ecosystem may affect the long-term balance in water and nutrient uptake and may alter the redistribution of nutrients in the canopy and the underlying soils.

Abstract 3554: Targeting chromatin remodeling complex in pediatric cancers

Abstract Chromatin accessibility plays critical roles in maintaining normal gene regulatory programs in healthy tissue. Aberrant chromatin accessibility triggered by abnormal activity of a variety of chromatin remodeling complexes is known to activate and maintain tumor proliferation. The most widely known of these complexes is the SWI/SNF (also called BAF) complex. Studies have shown that BAF regulates chromatin accessibility in a more global manner and its long-term inhibition or functional loss may lead to non-specific downstream effects in both tumor and normal tissue. Thus, there is a need to further probe understudied complexes, such as the Imitation Switch (ISWI) family of chromatin remodelers, to find more cancer specific functions that can provide mechanistic insights that pave the way for novel therapeutic discoveries. We have examined the functions of these chromatin complex in different type of pediatric cancers to estsablish the pre-clinical rationale for potential novel pediatric cancer therapy. We discovered that fusion protein positive rhabdomyosarcoma (FP-RMS), an aggressive sub-type of RMS characterized by chromosomal translocations resulting in gene fusions between PAX3/7 and FOXO1 is highly dependent on chromatin accessibility. This aggressive subtype exhibits a significant vulnerability in its dependence on the oncogenic transcription factor PAX3-FOXO1, yet like many other TFs, PAX3-FOXO1 is currently not considered a viable therapeutic candidate. We have then carefully examined the effect of chemical inhibition and chemical degradation of BAF complex function in FP-RMS and discovered that BAF complex globally regulates chromatin accessibility, is not specifically regulating FP function. We next examined the function of other chromatin remodeling complexes that might regulate FP function specifically in FP-RMS. We identified that some of other chromatin remodeling complex, such as Nuclear Remodeling Factor (NURF) complex, a member of the ISWI chromatin remodeling complex family, interacts with a critical fusion protein, PAX3/7-FOXO1, in FP-RMS. There is limited understanding surrounding the functions of NURF complex, particularly in pediatric cancer. Here, we then studied the key functions of FP regulated by variety of chromatin remodeling complex utilizing combined chemistry and biology method to elaborate the essential functions of PAX3/7-FOXO1 fusion protein. We have developed variety of chemical strategies to target these complexes, and utilize these tool compounds to delineate the chromatin remodeling complex regulated FP functions. This study showcased our approach to advance cancer research by combining the power of chemistry, chemical biology, structural biology, computational biology and cellular biology to identify novel mechanistic understanding as well as novel therapeutic approach for pediatric cancers. Citation Format: Jun Qi. Targeting chromatin remodeling complex in pediatric cancers. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3554.

Analysis of prestressing in old full-scale concrete members

The effective prestressing force is a key parameter that affects the performance of prestressed concrete members (PCM). In fact, the accurate determination of the residual prestressing force is crucial to assess existing PCM since it influences load-carrying capacities, in-service structural properties and remaining service life. The aging of structures, with limited functional capacity, implies a major problem that must be addressed without delay. Progress in the promotion of innovative solutions to extend the service life of structures depends on: (a) the availability of reliable indirect methods, since old PCM were usually no instrumented during casting; (b) the formulation of adequate diagnostics of the residual stress–strain state of structures; and (c) the availability of highly refined predictive tools. The implementation of these elements in the management and maintenance systems of PCM will serve to support decision making associated with structural assessment and to gather information to establish criteria for the design of more resilient PCM.Among the destructive methods available to empirically assess the actual condition of PCM, it can be found: crack initiation, crack re-opening and tendon cutting. As destructive methods inevitably cause structural damage and are not suitable for application to in-service structures, non-destructive methods or with conditions that only require aesthetic restitution (e.g. exposed tendon deformation, hole-drilling and saw-cuts) appear as an alternative of increasing interest.As a first step to obtain feed-back from several experimental tests carried out on unmonitored full-scale PCM over the years, this paper examines different techniques and methods used to evaluate the residual prestressing force, and also presents the deviations and uncertainties regarding predictions of short- and long-term prestress losses from main code models used in design. It is concluded that it is interesting to follow a non-destructive indirect testing methodology to be able to keep in service and monitor the current structures. This would make it possible to draw up a maintenance plan based on the condition of the PCM.

REal-world treatment outcomes after delayed intRavitreal therapy in center-involving diabetic macular edema – RETORT study

PurposeTo compare real-life data on delayed intravitreal treatment of diabetic macular edema (DME) patients to early treatment.MethodsIn this single-centre, retrospective, interventional, comparative study, DME patients were divided into two groups based on when they received treatment: Group 1 - received treatment within 24 weeks and Group 2 - at or after 24 weeks from the time of treatment advice. Visual acuity and central subfield thickness (CSFT) changes were compared at various time points. Reasons for delaying treatment were noted.ResultsThe study included 109 (Group 1–94; Group 2–15) eyes. When treatment was advised, demographic profile, diabetes duration, glucose control and VA between two groups were comparable. At this point, CSFT was higher in Group 1 than in Group 2 (p = 0.036). At injection time, Group 2 had better VA and lower CSFT than Group 1 (p < 0.05). Group 2’s VA (53.4 ± 12.67) was significantly lower than Group 1’s (57.38 ± 20.01) after 1-year treatment. At 1-year, CSFT decreased in Group 1 and increased in Group 2. Group 1 had mean improvement of + 7.6 letters and Group 2 had a decline of -6.9 letters. Group 2 required more intravitreal anti-VEGF (median – 3; IQR: 2–4), steroid injections (median – 4; IQR: 2–4) and focal laser sessions (median – 4; IQR: 2–4).ConclusionLate-treated DME eyes needed more injections and focal laser sessions than early treated eyes. Adherence to early treatment of DME in real-life will help prevent long-term vision loss.

Long-Term Prestress Loss Calculation Considering the Interaction of Concrete Shrinkage, Concrete Creep, and Stress Relaxation

In order to accurately calculate the long-term prestress losses of prestressed tendons, a time-varying model of long-term prestress loss considering the interaction between concrete shrinkage, creep, and the stress relaxation of prestressed tendons was constructed. Then, a method for calculating the long-term prestress losses of concrete structures was developed. A long-term prestress loss test of a prestressed concrete T-beam in a long-term field test environment was carried out. The measured values of long-term prestress losses are compared with the calculated results of JTG 3362-2018, AASHTO LRFD-2007, and the time-varying law model. The results show that the long-term effective tension of the T-beam decreases gradually with the increase in the load holding time. At the beginning of loading, the tensile force changes rapidly and then gradually slows down. The later the tensile age or the higher the initial loading stress level, the smaller the long-term prestress losses of the prestressed tendons. The long-term prestress loss values calculated by JTG 3362-2018, AASHTO LRFD-2007, and the time-varying law model increase with the increase in the load holding time. In the early stage of loading, the rate of change slows down and tends to be stable. The calculated results of JTG 3362-2018 and AASHTO LRFD-2007 are significantly different from the measured values. However, the calculated results of the time-varying law model are in good agreement with the measured values. The average coefficients of variation of the long-term prestress loss calculated by JTG 3362-2018, AASHTO LRFD-2007, and the time-varying law model are 17%, 10%, and 5%, respectively. The time-varying law model of the long-term prestress losses of prestressed tendons is accurate, and the long-term prestress loss of prestressed reinforcement can be predicted effectively.

Multihazard life-cycle cost optimization of active mass dampers in tall buildings

This article proposes an optimization-based-methodology for designing multiple active mass dampers (AMDs) in tall buildings in multihazard environments. A realistic cost of the AMD system is formulated as the objective-function, and the multihazard Life-Cycle-Cost (LCC) that represents the long-term hazard-related losses, is selected as the main performance-constraint. This allows joining winds and earthquakes in a single decision parameter. Additional constraints limit the dampers forces and strokes. To ensure stability of the actively controlled building, the LQR algorithm is nested within the formal optimization problem. In addition, for the first time in the context of AMDs, their masses are considered as design variables, emerging directly as an optimization output. As the LQR control law is not aimed at optimizing costs and LCC, the lower triangular matrices related to the LQR weighting matrices are used as additional design variables. Thus, their values converge throughout the optimization to optimize the formulated cost function while satisfying the constraints. As this strategy produces large-scale problems, an efficient gradient-based algorithm is developed, using the adjoint sensitivity analysis method. The framework is applied to several examples for a benchmark-building, providing consistent results. One example demonstrates that AMDs can offer similar performance to its passive TMDs counterpart, requiring a mass 40% lower.

Differential response of HBV Envelope-specific CD4+ T cells is related to HBsAg loss after stopping nucleos(t)ide analogue therapy.

Long-term maintenance of viral control, even HBsAg loss, remains a challenge for chronic hepatitis B (CHB) patients undergoing nucleos(t)ide analogue (NA) discontinuation. This study aimed to investigate the relationship between HBV-specific T cell responses targeting peptides spanning the whole proteome and clinical outcomes in CHB patients after NA discontinuation. Eighty-eight CHB patients undergoing NA discontinuation were classified as responders (remained relapse-free up to 96wk) or relapsers (relapsed patients who underwent NA re-treatment for up to 48 weeks and re-achieved stable viral control). HBV-specific T cell responses were detected at baseline and longitudinally throughout follow-up. We found responders had a greater magnitude of HBV Polymerase (Pol)-specific T cell responses than relapsers at baseline. After long-term NA discontinuation, simultaneously enhanced HBV Core- and Pol-induced responses were observed in responders. Particularly, responders with HBsAg loss possessed enhanced HBV Envelope (Env)-induced responses after short and long-term follow-up. Notably, CD4+T cells accounted for the predominance of HBV-specific T cell responses. Correspondingly, CD4-deficient mice showed attenuated HBV-specific CD8+T cell responses, reduced HBsAb-producing B cells, and delayed HBsAg loss; in contrast, in vitro addition of CD4+T cells promoted HBsAb production by B cells . Additionally, interleukin (IL)-9, rather than PD-1 blockade, enhanced HBV Pol-specific CD4+T cell responses. HBV-specific CD4+T cell responses induced by the targeted peptide possess specificities for long-term viral control and HBsAg loss in CHB patients undergoing NA discontinuation, indicating that CD4+T cells specific for distinct HBV antigens may endow with divergent antiviral potential.