Initial Loading Phase Research Articles

Predictive factors for Submacular Hemorrhage in Age-related Macular Degeneration: A Retrospective Study.

Little is known about the major risk factors for submacular hemorrhage (SMH). This study aimed to evaluate the factors associated with SMH in patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) receiving three consecutive loading doses of intravitreal aflibercept or ranibizumab injections. This retrospective cross-sectional study included 48 patients diagnosed with wAMD and PCV who completed three loading doses under a treat-and-extend regimen. Patients were divided into the SMH group (n=24) and the non-SMH group (age- and sex-matched without SMH). Intravitreal injections, agents, and optical coherence tomography (OCT) features were compared. In the SMH group, SMH occurred approximately 3.29 years after post-nAMD diagnosis. The non-SMH group received more intravitreal injections of aflibercept and brolucizumab during the follow-up period after the initial loading phase. The SMH group exhibited a higher prevalence of serous/hemorrhagic pigment epithelial detachments (PEDs) at the last visit before SMH occurrence compared to the non-SMH group. Patients with a PED increase in the past two visits showed a higher tendency in the SMH group. No other OCT features significantly correlated with SMH development. The presence of serous/hemorrhagic PEDs may indicate a higher risk of SMH, and eyes with these features should be closely monitored to prevent sudden and devastating visual loss caused by SMH.

Seepage-stress coupling characteristics of initial damaged glass fiber reinforced concrete under different loading conditions

Different loading methods induce variations in the macroscopic performance of the specimens. In this investigation, experiments were conducted on glass fiber reinforced concrete subjected to varying degrees of damage. Initially, axial compression loading and unloading were performed, followed by continuous axial compression loading. The study elucidates the evolution of permeability and strength characteristics of specimens under these two loading regimes. The experimental results delineate the trend of permeability and its corresponding strength attributes under complex stress paths. It was observed that during the axial compression loading and unloading phases, the permeability of the specimens follows a negative exponential function. As axial pressure increases, internal pores within the specimens were compacted, leading to a reduction in seepage pathways and a significant decline in permeability. At different stages of axial compression (0–5 MPa, 5–15 MPa, 15–25 MPa), the rate of permeability reduction diminishes progressively, with minimal change observed in the high-stress stage. During the unloading phase, due to incomplete recovery of plastic deformation, permeability shows only a limited increase, with the maximum recovery rate being less than 40 %. During the initial phase of continuous axial compression loading, the permeability first diminishes, subsequently entering an elastic stage where it stabilizes. However, upon reaching the point of instability failure due to crack propagation, permeability increases sharply. Additionally, as the number of freeze-thaw cycles rises, the degree of internal damage within the specimen escalates, manifesting as an increase in both pore size and quantity. Notably, the initial permeability and peak strength exhibited opposing trends: after 40 freeze-thaw cycles, initial permeability increased by 36 %, while peak strength decreased by 22 %.

Activity-Dependent Compensation at the Hip and Ankle at 8 Years After the Reconstruction of Isolated and Combined Posterior Cruciate Ligament Injuries

Background: After posterior cruciate ligament reconstruction (PCLR), functional deficits at the knee can persist. It remains unclear if neighboring joints compensate for the knee during demanding activities of daily living. Purpose: To assess long-term alterations in lower limb mechanics in patients after PCLR. Study Design: Descriptive laboratory study. Methods: A total of 28 patients who had undergone single-bundle unilateral isolated or combined PCLR performed stair navigation, squat, sit-to-stand, and stand-to-sit tasks at 8.2 ± 2.2 years after surgery. Motion capture and force plates were used to collect kinematic and kinetic data. Then, 3-dimensional hip, knee, and ankle kinematic data of the reconstructed limb were compared with those of the contralateral limb using statistical parametric mapping. Results: Side-to-side differences at the knee were primarily found during upward-driven movements at 8 years after surgery. The reconstructed knee exhibited lower internal rotation during the initial loading phase of stair ascent versus the contralateral knee (P = .005). During the sit-to-stand task, higher flexion angles during the midcycle (P = .017) and lower external rotation angles (P = .049) were found in the reconstructed knee; sagittal knee (P = .001) and hip (P = .016) moments were lower in the reconstructed limb than the contralateral limb. In downward-driven movements, side-to-side differences were minimal at the knee but prominent at the ankle and hip: during stair descent, the reconstructed ankle exhibited lower dorsiflexion and lower external rotation during the midcycle versus the contralateral ankle (P = .006 and P = .040, respectively). Frontal hip moments in the reconstructed limb were higher than those in the contralateral limb during the stand-to-sit task (P = .010); during squats, sagittal hip angles in the reconstructed limb were higher than those in the contralateral limb (P < .001). Conclusion: Patients after PCLR exhibited compensations at the hip and ankle during downward-driven movements, such as stair descent, squats, and stand-to-sit. Conversely, residual long-term side-to-side differences at the knee were detected during upward-driven movements such as stair ascent and sit-to-stand. Clinical Relevance: After PCLR, side-to-side differences in biomechanical function were activity-dependent and occurred either at the knee or neighboring joints. When referring to the contralateral limb to assess knee function in the reconstructed limb, concentric, upward-driven movements should be prioritized. Compensations at the hip and ankle during downward-driven movements lead to biases in long-term functional assessments.

Progressive collapse behaviour of earthquake-damaged interior precast concrete joints with headed bars and plastic hinge relocation

This study investigated progressive collapse behaviour of earthquake-damaged interior precast concrete (PC) joints with headed bars. The main objective was to quantify the impact of slight and moderate earthquake damage on their residual collapse resistance. The research began with a numerical investigation to understand the interaction between a 2D frame’s global response to seismic loading and its local response during a threat-independent progressive collapse event. Additionally, a separate set of numerical studies examined interior PC joints under cyclic loading to determine maximum drift ratio demands, yielding 2.5% for slightly and 3.5% for moderately damaged joints. Subsequently, an experimental programme under quasi-static loading conditions was conducted on five interior PC joints under cyclic loading, followed by progressive collapse resistance tests. Test results indicated that damaged joints exhibited flexural and catenary action during progressive collapse, but compressive arch action could not be mobilised due to residual cracks from the initial cyclic loading phase. Comparing damaged joints to fully intact ones from a companion study revealed deterioration in stiffness and deformation capacity during a subsequent progressive collapse, with degree of severity proportional to the extent of damage sustained in the cyclic loading phase. Relative to the intact joints without being subjected to cyclic loading, moderately damaged specimens exhibited a degradation of 63% in stiffness and 38% in deformation capacity, compared to slightly damaged specimens, which showed reductions of 38% in stiffness and 28% in deformation capacity. In contrast, strain hardening of steel bars in both slightly and moderately damaged specimens led to slightly greater collapse resistance than the intact joints. Additionally, failure mode shifted from ductile fracture to premature pull-through failure of headed bars in moderately damaged specimens. In this regard, in post-earthquake progressive collapse assessment, it is recommended to use maximum crack width thresholds of 0.2 to 1.0 mm for slight damage and 1.0 to 2.0 mm for moderate damage.

Mechanical insights into jawbone characteristics under chronic kidney disease: A comprehensive nanoindentation approach

The mechanical properties of the jawbone play a critical role in determining the successful integration of dental prostheses. Chronic kidney disease (CKD) has been identified to abnormally accelerate bone turnover rates. However, the impact of CKD on the mechanical characteristics of the jawbone has not been extensively studied. This study sought to evaluate the time-dependent viscoelastic behaviors of rat jawbones, particularly in the scenarios both with and without CKD. We hypothesized that CKD might compromise the bone's innate toughening mechanisms, potentially owing to the time-dependent viscoelasticity of the bone matrix proteins. The maxillary and mandibular bones of Wistar rats were subjected to nanoindentation and Raman micro-spectroscopy. Load-hold-displacement curves from the cortical regions were obtained via nanoindentation and were mathematically characterized using a suitable viscoelastic constitutive model. Raman micro-spectroscopy was employed to identify nuanced vibrational changes in local molecular structures induced by CKD. The time course of indenter penetration onto cortical bones during the holding stage (creep behavior) can be mathematically represented by a series arrangement of the Kelvin–Voigt bodies. This configuration dictates the overall viscoelastic response observed during nanoindentation tests. The CKD model exhibited a reduced extent of viscoelastic contributions, especially during the initial ramp loading phase in both the maxillary and mandibular cortical bones. The generalized Kelvin–Voigt model comprises 2 K–Voigt elements that signify an immediate short retardation time (τ1) and a subsequent prolonged retardation time (τ2), respectively. Notably, the mandibular CKD model led to an increase in the delayed τ2 alongside an increase in non-enzymatic collagen cross-linking. These suggest that, over time, CKD diminishes the bone's capability for supplementary energy absorption and dimensional recovery, thus heightening their susceptibility to fractures.

MWCNT-reinforced silicone's dual response to human and mechanical motion: Exploring strain sensing behavior and practical applications

This study investigates the human motion sensing capabilities of silicone rubber (SR) composites reinforced with multi-walled carbon nanotubes (MWCNTs). It focuses on assessing the responsiveness of the composites to both compressive and tensile deformations, replicating motions from machines to human movements. The analysis underscores the enhanced sensitivity of the 3 parts per hundred (phr) compressive sample, with gauge factors of 7.5 and 14.44 at distinct linear ranges under 30% strain. During forefinger and thumb pressing, the relative change in resistance was 160 and 350, respectively. Additionally, the study examines the 5 phr sample, revealing a significant 346.67% increase in relative resistance changes during the initial cyclic loading phase under 30% tensile deformation compared to the compression sample. The mechanical properties are also evaluated, showing the 5 phr compressive sample possessing a compressive modulus 180.09% higher than the modulus of the unfilled specimen (1.246 MPa), along with a hysteresis loss of 37.24 kJ. Furthermore, the tensile modulus of the 5 phr specimen exceeds that of the unfilled rubber by 218.84%. The developed composites hold promise for creating sensors capable of tracking athletes' movements in real time, offering immediate performance feedback and post-processing analysis. Moreover, these materials could contribute to the design of rehabilitation devices aimed at assisting individuals with hand injuries in regaining their agility and mobility.

Strength Reduction Method for the Assessment of Existing Large Reinforced Concrete Structures

This work presents a new developed assessment methodology based on strength reduction and finite element methods which is suitable for existing large reinforced concrete structures commonly used in hydraulic constructions. The methodology is based on a reloading phase of the finite element model and is preceded by an intermediate reduction phase of concrete tensile strength and an initial loading phase up to service level. Rosenblueth’s point estimate method was used to compute a global resistance factor and to deduce a design resistance value of the structure. After validations, the methodology was applied to two existing complex and large hydraulic structures: a spiral case and a draft tube. If compared with existing methodologies using sophisticated non-linear finite element methods, the developed approach is simpler, more practical, and provides results that are on the conservative side. Considering the difficulties in characterizing the tensile peak and post-peak strength of concrete, along with uncertainties regarding the damage conditions of facilities, the developed methodology is deemed robust and well suited for assessing existing critical large reinforced concrete infrastructures.

Difference in immunosuppressant dose requirement when transitioning to isavuconazole from other azoles in thoracic transplant recipients.

The triazole antifungal isavuconazole (ISAVU) is used for prevention and treatment of fungal infections in solid organ transplant (SOT). SOT recipients commonly need to transition from one azole to another due to breakthrough infection, toxicity, or other reasons. The purpose of our study was to evaluate the effect of ISAVU on immunosuppressant concentrations in thoracic transplant recipients when ISAVU was started de novo or transitioned from another azole. We conducted a single-center retrospective cohort study including 68 patients (51 lung, 14 heart, and 3 heart/lung transplant). Concentration to dosage ratios (C/D) of immunosuppressants were assessed at baseline, day 3, and weekly for 9 weeks. When starting ISAVU de novo, we observed a temporary doubling of tacrolimus exposure. Cyclosporine and sirolimus required dose decreases. Tacrolimus C/D increased by 110% at day 3 in patients started on ISAVU de novo then returned to baseline C/D ± 17% weeks 2-9 (n = 8). One cyclosporine patient started on ISAVU de novo had variable C/D, and C/D increased by 219% ± 72% in 2 sirolimus patients. When transitioning from other azoles, tacrolimus and cyclosporine required about twice the initial dose. After week 1, tacrolimus C/D decreased by 53% ± 6% in patients transitioned from posaconazole (n = 33), voriconazole (n = 14), or fluconazole (n = 2). Cyclosporine C/D decreased by 45% ± 16% in patients transitioning from other azoles (posaconazole [n = 2], voriconazole [n = 2], fluconazole [n = 1]). Sirolimus C/D decreased by 73% ± 13% in patients transitioned from posaconazole (n = 7). Aside from the initial loading phase, ISAVU had a lesser degree of interaction with immunosuppressants than other azoles in loading phase, ISAVU had a lesser degree of interaction with immunosuppressants than other azoles in adjustments for the 4-week period after initiating antifungal therapy with ISAVU or switching from another agent.

Variation characteristics of key dynamic measurement signals of anchor bolts with different anchorage qualities under pull-out loads

Pull-out load and the cement-sand ratio (CSR) can affect the non-destructive testing (NDT) results of anchor bolts. Therefore, in this article, NDT experiments were conducted on both fully and defectively grouted anchor bolts, and variation patterns of key dynamic testing signal parameters were analyzed. A longitudinal vibration model of defectively grouted anchor bolts considering dynamic and static damping was proposed, and simulated NDT of anchor bolts with varying qualities. The results indicated that grouting defects resulted in an increase in wave velocity, along with a decrease in the fundamental frequency and dynamic stiffness of anchor bolts. When grouting defects and pull-out load acted concurrently, the fundamental frequency, and dynamic stiffness of the defectively grouted anchor bolts were consistently smaller than those of fully grouted ones during the initial loading phase. With pull-out load increasing, wave velocity decreased first, then increased; fundamental frequency increased, followed by a decrease; dynamic stiffness rose. When the CSR of defectively grouted anchor bolts was reduced, wave velocity decreased, fundamental frequency increased slightly, and a substantial increase in dynamic stiffness was observed. Pull-out loads were more sensitive to anchor bolt key dynamic signals than defects and CSR. Simulated validation demonstrated the reliability of the proposed theory.

Emicizumab Use in Infancy: A Survey of United States Pediatric Hemophilia Treatment Center Medical Directors

Introduction: Emicizumab, a bispecific antibody directed against activated factor IX and factor X, is a subcutaneous non-factor prophylactic option for individuals with hemophilia A (HA). The safety and efficacy of emicizumab has been demonstrated in both adult and pediatric patients. It was approved by the United States (U.S.) Food and Drug Administration for routine prophylaxis to prevent or reduce bleeding episodes in individuals with HA, ages newborn and older, both with (2017) and without (2018) factor VIII (FVIII) inhibitors. Despite this approval, data on emicizumab in infants are limited. The HAVEN 2 pediatric clinical trial had only two infants under 24 months of age, though interim analysis of the HAVEN 7 trial demonstrated emicizumab efficacy and safety in infants. Thus, the optimal use of emicizumab in infants under 12 months of age remains unclear. The objective of this study was to understand the rationale and treatment decisions regarding initiation of emicizumab prophylaxis in children under 12 months of age among pediatric Hemophilia Treatment Center (HTC) Medical Directors in the U.S. Methods: An electronic survey was conducted from April to May 2023 of U.S. HTC Medical Directors via REDCap. Invitations were sent to all individuals listed as HTC Directors at pediatric medical centers on the Center for Disease Control and Prevention database. The survey included two hemophilia patient case scenarios associated with 15 multiple-choice questions and additional free-text options. The first case was of a 9-month-old male with severe HA, without prior bleeding history or exposure to FVIII, who presented for his initial visit to an HTC. The second case was a 3-month-old male with severe HA receiving FVIII replacement therapy for an intracranial hemorrhage. This study was approved by the Baylor College of Medicine Institutional Review Board. Results: Overall, 33 of 97 (34%) pediatric HTC Medical Directors participated in the survey. One survey was minimally completed and excluded for a total of 32 surveys included in the final analysis. The majority of participants had over 15 years of experience caring for patients with HA (n=21, 65.6%) and represented HTCs with over 250 patients (n=22, 68.8%; Table 1). For previously untreated or minimally treated infants (Case 1), 96.9% of responses (n=31) stated they would consider starting emicizumab prophylaxis; 45.2% (n=14) would consider initiating it as young as 1 week of age. The most common reason cited for starting emicizumab in an infant was to prevent an intracranial hemorrhage (n=17, 53.1%) followed by the desire to avoid central line placement (n=7, 21.9%). The majority of respondents did not wait for a minimum number of factor exposure days prior to starting emicizumab (n=31, 96.9%) nor did they report regularly exposing infants to FVIII concentrate until 50 EDs are reached (n=29, 90.6%). After the initial loading phase, the majority of respondents selected an emicizumab dosing regimen of every 2 weeks (n=19, 59.4%). There was a varied approach to monitoring for inhibitor development after starting emicizumab; 40.6% (n=13) reported monitoring at regular intervals between every 6 to 24 months, whereas 46.8% (n=15) did not report following a set schedule and instead obtain FVIII inhibitor testing only after FVIII exposure (Table 2). For infants receiving FVIII replacement for treatment of an intracranial hemorrhage (Case 2), 96.9% (n=31) of participants stated they would transition to emicizumab as a prophylactic agent. Over half (n=16, 51.6%) stated they would initiate emicizumab during the treatment period for the hemorrhage rather than waiting until therapy completion. For providers that use emicizumab in moderate hemophilia, emicizumab was reported to be used routinely by 27.3% (n=6) and on a case-by-case basis in 40.9% (n=9, Table 2) in infants with moderate HA. Conclusion: Pediatric HTC Medical Directors in the U.S. report commonly utilizing emicizumab in infants under 12 months of age despite the lack of robust data in this age group. This practice is consistent with recommendations by the National Hemophilia Foundation's Medical and Scientific Advisory Council. With the completion of clinical trials focused on infants with HA, along with additional long-term outcomes data, more specific guidance around initiation, follow-up and monitoring may be available to inform the optimal management for these patients.

Creep properties and constitutive model of salt rocks under a slow cyclic loading path

The construction of compressed-air energy storage (CAES) plants using the huge space created by salt rock mining is a key means of optimizing China's energy structure. The creep properties of salt rock are vital parameters for ensuring the long-term, stable operation of CAES plants. According to the operation mode of CAES plants, creep tests were conducted on salt rock under the influence of slow loading and unloading. The results indicated that the slow loading and unloading history locally changed the creep development process but did not affect the overall creep process. Additionally, the steady state creep rate of the salt rock depended mainly on the magnitude of external stress. Moreover, the creep test was monitored simultaneously using acoustic emission (AE) technology, and the distribution of the AE absolute energy during the initial loading phase and steady state creep phase satisfied the power law. To more accurately describe the creep characteristics of the salt rock under the influence of slow loading and unloading, a full-process creep constitutive model of salt rock was constructed using state variable, fracture expansion factor, and unloading factor.

Evaluation of stress path and load rate effects on rock strength using compression testing data for Stanstead Granite

Compression testing schemes that induce failure in rock specimens primarily through a reduction in confining stress have become increasingly common in recent years. Despite this, the interpretation of the results from such studies are fraught with complications due to the large number of factors that can influence the outcome of such tests relative to standard compression tests that follow a loading path. Among these, unloading rate is especially significant, as it has the potential to both influence peak strength and total test time (i.e. time-dependent effects). In this study, we present a framework to convert unloading rates into equivalent loading rates to facilitate comparison with standard compression test results as well as comparisons across rock types. We then present the results of a suite of 39 compression tests, including strain-controlled standard UCS and triaxial tests, constant deviatoric stress unloading triaxial tests, diagonal stress path unloading triaxial tests, and load-controlled standard triaxial tests. Based on comparison of load-controlled and strain-controlled standard compression tests, it is concluded that strain-controlled tests produce appreciably lower peak strength values, even if relevant ISRM Suggested Methods and ASTM Standards are followed in both cases. Additionally, the different control modes produce different volumetric strain responses up to the point of peak strength. A detailed comparison of load-controlled test results from standard triaxial tests and unloading triaxial tests with failure points at σ3 ≈ 1 MPa reveals that diagonal stress path unloading tests produce comparable peak strength values to standard load-controlled tests. Although the observed trend in the constant deviatoric stress unloading triaxial test data corresponds to lower peak strength values than those obtained using standard load-controlled tests, we attribute this discrepancy to time-dependent damage effects and/or minor damage accumulation during the initial loading phase of the tests rather than to the difference in stress paths.

Controlled randomized open label clinical study comparing the safety and efficacy of loading schedules in vitamin D deficient patients

Rapidly restoring vitamin D levels to normal might be desirable in certain clinical situations. Larger doses of supplementation, have been shown to increase bone loss and the risk of falls. The optimal way to perform vitamin D loading safely and effectively is still not well elucidated. Our study was aimed to assess the safety and efficacy of two oral vitamin D loading protocols. Sixty-nine subjects with vitamin D deficiency (25OH-vitamin D (25(OH)D) < 20 ng/ml) were included. Thirty-five participants received 30 000 IU of vitamin D3 per week for 10 weeks (group Slower Loading Dose (SLD)) and thirty-four received 30 000 IU twice weekly for 5 weeks (group Moderate Loading Dose (MLD)) resulting in a loading dose of 300 000 IU for all subjects. Following this initial loading phase, both groups received 30 000 IU biweekly for 4 weeks to test whether the recommended daily vitamin D supplementation in range of 2000 IU dose-equivalent could maintain the achieved levels. Seventy-nine percent of those subjects treated in group SLD and everyone in group MLD achieved a 25(OH)D level of 30 ng/ml, which is the lower limit of the recommended normal range in Hungary. The mean increase in 25(OH)D was significantly higher in group MLD than in group SLD (38.6 ± 1.80 ng/ml vs 46,6 ± 1.80 ng/ml). No significant decrease was observed with the administration of the maintenance dose. There were no clinically significant changes in serum or urine calcium, and bone biomarkers in either group. Both protocols were found to be safe and effective, but the five-week dosing caused a significantly greater increase in 25(OH)D. A maintenance dose applied for four weeks after the loading protocol did not raise 25(OH)D levels further but maintained the achieved increase. The administration of 30 000 IU of vitamin D3 twice weekly for five weeks is a rapid, effective and safe way to treat vitamin D deficiency in vitamin D deficient patients.

Effect of Debonding on Axial Response of Concrete Filled Steel Tubular Columns

The axial strength and ductility of concrete filled steel tubes is significantly improved due to two major factors namely, firstly due to confining effect provided by steel tube, and secondly due to the synergistic interaction between steel tube and concrete core. Sometimes, the contact between concrete core and steel tube is vanished and debonding between concrete core and steel tube (normal referred as gap) occurs owing to various reasons such as improper compaction, shrinkage in concrete, lack of curing of encased concrete, and due to non-uniform distribution of load at column top. Due to occurrence of gap, the composite action between concrete core and steel tube no longer remains effective the concrete core becomes unconfined in the initial phase of loading, consequently, the axial load carrying capacity of the concrete filled steel tubular (CFST) column decreases. The aim of this paper is to numerically investigate the effect of the gap between concrete core and steel tube on the axial load-deformation response and to Comparisons the predicted column strengths according to the Eurocode-4. In the present study, the gap between square section concrete core and encasing steel tube is considered on all the four sides with the magnitude of gap as 1 mm and 2 mm. Moreover, in order to investigate the effect of the gap on different size of square section CFST columns, keeping the length of column and steel tube thickness as constant 540 mm and 3.8 mm respectively, the side length of square section CFST column has been varied between 140 mm to 200 mm at an interval of 20 mm. The nonlinear finite element analysis of the CFST columns has been performed using the Abaqus where the C3D8R element has been used to discretize the concrete core as well as steel tube and the Drucker-Prager model has been used to simulate plastic behaviour of concrete. It has been observed that the presence of gaps between concrete core and steel tube significantly reduces the axial strength square CFST column.

Robotic ankle control can provide appropriate assistance throughout the gait cycle in healthy adults.

Ankle foot orthoses are mainly applied to provide stability in the stance phase and adequate foot clearance in the swing phase; however, they do not sufficiently assist during the entire gait cycle. On the other hand, robotic-controlled orthoses can provide mechanical assistance throughout the phases of the gait cycle. This study investigated the effect of ankle control throughout the gait cycle using an ankle joint walking assistive device under five different robotic assistance conditions: uncontrolled, dorsiflexion, and plantar flexion controlled at high and low speeds in the initial loading phase. Compared with the no-control condition, the plantar flexion condition enhanced knee extension and delayed the timing of ankle dorsiflexion in the stance phase; however, the opposite effect occurred under the dorsiflexion condition. Significant differences in the trailing limb angle and minimum toe clearance were also observed, although the same assistance was applied from the mid-stance phase to the initial swing phase. Ankle assistance in the initial loading phase affected the knee extension and ankle dorsiflexion angle during the stance phase. The smooth weight shift obtained might have a positive effect on lifting the limb during the swing phase. Robotic ankle control may provide appropriate assistance throughout the gait cycle according to individual gait ability.

Experimental and numerical evaluation of the effects of interaction between multiple small holes and a single notch on the mechanical behavior of artificial gypsum specimens

The mechanical behavior of cubic gypsum specimens containing five small circular holes in a linear configuration and a single notch under uniaxial compression test were studied to evaluate interactions between these flaws during crack development under loading. Multiple angles between the line of holes and the horizontal axis were evaluated (15°, 45°, and 75°), as were different notch apertures (2, 4, 6 and 8 mm). Acoustic emission (AE) data were used to evaluate the fracture development process in each case. Following the experiments, numerical simulations of the tests were conducted using the particle flow code (PFC2D). The compressive strengths of the specimens were found to be associated with the failure mechanism and fracturing geometry, which were in turn controlled by the geometric attributes of the flaws considered. The compressive strength of specimens were affected by the number of tensile cracks. The induced tensile cracked number were increased by decreasing the joint length. Only few AE events were detected in the initial phase of loading, but then AE hits grew rapidly prior to reaching the peak stress. The AE hits increased by increasing the filling thickness. Failure pattern and compressive strength of specimens were nearly similar in both numerical and experimental approaches.

A Randomized, Controlled Trial of Treat-and-Extend vs. Pro Re Nata Regimen for Neovascular Age-Related Macular Degeneration.

PurposeTo compare the efficacy and safety of conbercept using a treat-and-extend (T&E) regimen vs. a pro re nata (PRN) regimen in Chinese patients with neovascular age-related macular degeneration (nAMD).MethodsThis was a randomized, multicenter, non-inferiority study. After an initial loading phase of three consecutive monthly intravitreal injections of 0.5 mg Conbercept, the patients were treated to PRN or T&E regimen. The prespecified retreatment criteria was defined as a more than 5-letter decrease in BCVA from the previous visit or any evidence of new retinal hemorrhages, or the presence of any IRF and any SRF of more than 200 μm in height at the sub-foveal center. The primary outcome was the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months, with a prespecified non-inferiority limit of −5 letters.ResultsFrom July 2016 through August 2018, 141 participants were allocated and treated (T&E, n = 69; PRN, n = 72). About one fifth of the overall participants were dropped out during the 12-month follow-up (28/141, 19.9%), and about one thirds of the overall participants were lost during the 24-month follow-up (51/141, 36%). At 2 years, mean BCVA letter improvement was + 4.0 in the T&E group vs. + 5.1 in the PRN group, and T&E regimen was not non-inferior to PRN regimen [difference, −1.169 letters; 95% confidence interval (CI): −6.864 ∼ 4.526]. Subgroup analyses also demonstrate the similar results in PCV patients, naive patients and no-naive patients. The mean decrease in central subfield thickness were 180 ± 165 μm in the T&E group and 247 ± 230 μm in the PRN group, respectively. The patients in the PRN group had required significantly fewer injections than those in the T&E group (12.4 vs. 14.6 injections, P = 0.041). The types and rates of adverse events were comparable in the two treatment groups.ConclusionThese findings suggest that the T&E regimen was not non-inferior to the PRN regimen in patients with nAMD in terms of BCVA outcomes through 24 months.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT02802657.

EFFECT OF RANIBIZUMAB AND AFLIBERCEPT ON RETINAL PIGMENT EPITHELIAL DETACHEMENT, SUBRETINAL AND INTRARETINAL FLUID IN AGE-RELATED MACULAR DEGENERATION.

The aim of the study was to compare the effect of three initial doses of the anti-VEGF ranibizumab and aflibercept medication on serous pigment epithelial detachment (PED), subretinal fluid (SRF) and intraretinal fluid (IRF) in the macula of treatment naive neovascular AMD (nvAMD) patients. The cohort consists of 148 patients, of which 74 patients were treated with ranibizumab (51 females and 23 males) and 74 with aflibercept (46 females and 28 males). The data was recorded prospectively from the moment of diagnosis and start of treatment for a period of 3 months. At the moment of diagnosis and 3 months later, an OCT examination (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany) was performed. The OCT examination included a macular scan with 25 scans. Using the OCT instrument software, we measured the maximum anterior-posterior elevation of serous PED, the highest thickness of SRF and the largest diameter of the intraretinal cystic space. The statistical significance of differences between groups was evaluated using the t-test for continuous data and the Fisher exact test for categorical data. Changes in values of continuous variables over time were evaluated using the Wilcoxon paired test. Paired comparisons of binary parameters were determined by the McNemar test. Full regression of PED, SRF and IRF occurred in 3 (4.1%), 25 (39%) and 20 (51%) patients treated with ranibizumab, and in 5 (7.9%, p = 0.470), 28 (47%, p = 0.470) and 25 (57%, p = 0.827) patients treated with aflibercept, respectively. The average regression of PED, SRF and IRF was -60.4 &#956;m (median -37.5 &#956;m), -84.3 &#956;m (median -85 &#956;m) and -109.3 &#956;m (median -81 &#956;m) in patients treated with ranibizumab, and -46.3 &#956;m (median -30 &#956;m, p = 0.389), -127.7 &#956;m (median -104 &#956;m, p = 0.096) and -204.4 &#956;m (median -163 &#956;m, p = 0.005) in patients treated with aflibercept, respectively. We did not show a statistically significant difference in the regression rates of PED, SRF and IRF between the ranibizumab and aflibercept groups. (in patients with IRF after adjustment of the higher baseline IRF volumes in patients treated with aflibercept, p = 0.891). We are convinced that ranibizumab and aflibercept have the same effect on serous PED, SRF and IRF in the macula in patients with treatment naive nvAMD during the initial loading phase.

Prediction of the short-term efficacy of anti-VEGF therapy for neovascular age-related macular degeneration using optical coherence tomography angiography

BackgroundTo evaluate whether the specific choroidal neovascularization (CNV) characteristics measured using optical coherence tomography angiography (OCTA) can predict the 6-month prognosis of neovascular age-related macular degeneration (nAMD) after anti-vascular endothelial growth factor (anti-VEGF) therapy.MethodsPatients with type 1, type 2, or mixed-type neovascularization (NV) were prospectively included. Participants underwent an initial loading phase of three consecutive monthly intravitreal injections of Conbercept (0.5 mg) and were switched to a pro re nata (PRN) treatment strategy. OCTA images were evaluated for eyes that underwent follow-up assessments for more than 6 months. CNV lesions were manually segmented, and the CNV area, vessel area, greatest vascular caliber (GVC), and greatest linear dimension (GLD) were compared between responders and non-responders. Two masked graders independently measured the above-mentioned parameters using OCTA, and consistency was assessed using the intraclass correlation coefficient (ICC) values. Multiple logistic regression analysis was performed to evaluate the effect of a 3-month change in the CNV area, GLD, and GVC on the 6-month response to anti-VEGF agents.ResultsAmong the 60 eyes of 60 patients with nAMD, 39 were responders and 21 were non-responders. The proportion of CNV types was significantly different between responders and non-responders (P = 0.009). Patients with type 2 or mixed NV seemed more likely to respond to the treatment (28.2% vs. 0.0%, and 30.8% vs. 23.8%, respectively). The change in GVC showed a significant difference between responders (− 4.98 ± 17.17 μm) and non-responders (11.01 ± 14.10 μm) after three monthly intravitreal anti-VEGF injections. Multiple logistic regression analysis showed that only the change in GVC remained significant after controlling for baseline GVC, injection number, and CNV type (adjusted OR = 1.083; P = 0.008).ConclusionsType 2 and mixed-type NV were significantly associated with a better response to anti-VEGF therapy. Changes in GVC after 3 months of treatment were significantly associated with a response to anti-VEGF therapy at 6 months.

Study on Crack Classification Criterion and Failure Evaluation Index of Red Sandstone Based on Acoustic Emission Parameter Analysis

The acoustic emission (AE) characteristics of rock during loading can reflect the law of crack propagation and evolution in the rock. In order to study the fracture mode in the process of rock fracture, the AE characteristics and crack types of red sandstone during fracture were investigated by conducting Brazilian indirect tensile tests (BITT), direct shear tests (DST), and uniaxial compression tests (UCT). The evolution law of AE event rate, RA and AF values, and the distribution law of RA–AF data of red sandstone samples in three test types were analyzed. Based on the kernel density estimation (KDE) function and the coupling AE parameters (RA–AF values) in DST and BITT, the relatively objective dividing line for classifying tensile and shear cracks was discussed, and the dividing line was applied to the analysis of fracture source evolution and the failure precursor of red sandstone. The results show that the dividing line for classifying tensile and shear cracks of red sandstone is AF = 93RA + 75. Under uniaxial compression loading, the fracture source of red sandstone is primarily shear source in the initial phase of loading and tensile source in the critical failure phase, and the number is far greater than shear source. K = AF/(93RA + 75) can be defined as the AE parameter index, and its coefficient of variation CV (k) can be used as the failure judgment index of red sandstone. When CV (k) &lt; 1, it can be considered that red sandstone enters the instability failure phase.