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Changes in running strike pattern affect ankle and knee mechanics, but little is known about the influence of strike pattern on the joints distal to the ankle. The purpose of this study was to explore the effects of forefoot strike (FFS) and rearfoot strike (RFS) running patterns on foot kinematics and kinetics, from the perspectives of the midtarsal locking theory and the windlass mechanism. Per the midtarsal locking theory, we hypothesized that the ankle would be more inverted in early stance when using a FFS, resulting in decreased midtarsal joint excursions and increased dynamic stiffness. Associated with a more engaged windlass mechanism, we hypothesized that a FFS would elicit increased metatarsophalangeal joint excursions and negative work in late stance. Eighteen healthy female runners ran overground with both FFS and RFS patterns. Instrumented motion capture and a validated multi-segment foot model were used to analyze midtarsal and metatarsophalangeal joint kinematics and kinetics. During early stance in FFS the ankle was more inverted, with concurrently decreased midtarsal eversion (p < 0.001) and abduction excursions (p = 0.003) but increased dorsiflexion excursion (p = 0.005). Dynamic midtarsal stiffness did not differ (p = 0.761). During late stance in FFS, metatarsophalangeal extension was increased (p = 0.009), with concurrently increased negative work (p < 0.001). In addition, there was simultaneously increased midtarsal positive work (p < 0.001), suggesting enhanced power transfer in FFS. Clear evidence for the presence of midtarsal locking was not observed in either strike pattern during running. However, the windlass mechanism appeared to be engaged to a greater extent during FFS.

By utilizing hydrogen as an eco-friendly energy source, many metals are exposed to gaseous (pressurized) hydrogen. High-strength steels with an ultimate tensile strength of 800 MPa and above are especially susceptible to hydrogen-induced fracturing, also referred to as hydrogen embrittlement (HE). Both the microstructure and phase fractions within the steel, as well as lattice distortion, carbide precipitation, residual stress, etc., significantly affect the susceptibility to HE. Among others, one important cause for this observation is found in the locally varying hydrogen solubility within different microstructural phases such as martensite, bainite, pearlite, and ferrite. Both a thorough understanding of the HE mechanisms and taking countermeasures in the form of alloying design require an accurate analysis of local diffusive hydrogen concentrations within the material. Thermal analysis methods such as Thermal Desorption Mass Spectrometry only display an integral hydrogen concentration throughout the whole sample volume. To analyze the local diffusive hydrogen concentration, novel measuring techniques with a high special resolution must therefore be utilized. The current research presents first-of-its-kind hydrogen analyses by means of the electrochemical microcapillary cell. Using a 10 µm tip opening diameter allows for conducting local diffusive hydrogen measurements within individual grains of multi-phase carbon steel C60E (1.1221). The results confirm that hydrogen is distributed heterogeneously within multi-phase steels. Considering the individual phase fractions and the respective local diffusive hydrogen concentrations, a total diffusive hydrogen concentration can be calculated. The obtained value is in good agreement with reference thermal hydrogen analyses. Our results suggest that electrochemical microcapillary cell measurements offer great potential for further studies, which will provide a better understanding of HE and local hydrogen accumulation.

Both kinematics and kinetics of the lower limb have been shown separately to be related with a history of tibial stress fractures (TSFs) in female runners. However, it is likely that these factors interact together to increase the risk of a TSF. This study was conducted to determine which combination of kinematic and kinetic factors are the best predictors of retrospective TSF in female distance runners. Total 30 female runners who had previously sustained a TSF were recruited, along with an age and mileage matched control group ( n=30). Subjects ran overground at 3.7 m/s while kinematic and kinetic data were recorded. Five trials from each subject were used for data analysis and ensemble means were calculated for both groups. The kinematic variables of peak hip adduction (HADD), peak knee internal rotation (KIR) and knee adduction (KADD), peak rearfoot eversion (RFEV) were entered into a binary logistic regression along with the kinetic variables of vertical instantaneous load rate (VILR) and absolute free moment (FM). The variables HADD, FM and RFEV were able to correctly predict a history of TSF in 83% of cases. Increases in HADD, FM and RFEV (odds ratios of 1.29, 1.37 and 1.18) were associated with an elevated risk of having a history of TSF. The addition of VILR, KIR and KADD did not improve the ability to predict previous injury. Based on these results, HADD, FM and RFEV appear to be the most important of the variables of interest in terms of predicting retrospective TSF in female runners.

Children with end-stage renal disease (ESRD) frequently require more than one kidney transplantation (KT) during their lifetime due to limited graft longevity. Despite this clinical reality, few studies have evaluated long-term outcomes following repeat pediatric KT. We conducted a retrospective single-center study analyzing 120 KTs performed in 89 pediatric recipients between 1993 and 2024. Outcomes included graft function, postoperative complications, and long-term graft and patient survival. Recipients were stratified into primary (1KT), second (2KT), and third (3KT) transplantation groups. At the time of 1KT, median recipient age was 11.0 years (IQR 7.0, 14.5). Living donation accounted for 16.7% of procedures. Graft failure within five years occurred in approximately 20% of 1KT cases. Half of these patients received a 2KT after a median waiting time of 4.6 years (IQR 2.1, 9.0). Rates of early postoperative complications and kidney function were comparable across groups. Kaplan–Meier analysis revealed significantly improved long-term survival following 2KT compared to failed 1KT ( p  = 0.023). Repeat kidney transplantation is a feasible and effective strategy for pediatric ESRD patients. Second transplants provide long-term outcomes comparable to, or better than, initial grafts. Multicenter prospective studies are warranted to confirm these findings.

This article identifies reputation-risk-relevant factors for banks, and the focus will be placed on the development of an indicator-based model for the assessment of reputation. Requirements and insights are based on a survey of credit institutions in Germany and Switzerland, which have been predominantly affected during the financial crisis by aptly nascent risks and which are thereby also partially affected even today. Reputation level can be considered as a temporally dynamical phenomenon which predominantly develops depending on the changes in the reputation drivers and expectations of the groups of stakeholders. This control parameter can be determined with the aid of Reputation Index Points (RIP). Efficient reputation risk management can, in the future, help prevent negative spillover effects from banks which face difficulties from the society or the taxpayers.

An accurate blood‐based RAS mutation assay to determine eligibility of metastatic colorectal cancer (mCRC) patients for anti‐EGFR therapy would benefit clinical practice by better informing decisions to administer treatment independent of tissue availability. The objective of this study was to determine the level of concordance between plasma and tissue RAS mutation status in patients with mCRC to gauge whether blood‐based RAS mutation testing is a viable alternative to standard‐of‐care RAS tumor testing. RAS testing was performed on plasma samples from newly diagnosed metastatic patients, or from recurrent mCRC patients using the highly sensitive digital PCR technology, BEAMing (beads, emulsions, amplification, and magnetics), and compared with DNA sequencing data of respective FFPE (formalin‐fixed paraffin‐embedded) tumor samples. Discordant tissue RAS results were re‐examined by BEAMing, if possible. The prevalence of RAS mutations detected in plasma (51%) vs. tumor (53%) was similar, in accord with the known prevalence of RAS mutations observed in mCRC patient populations. The positive agreement between plasma and tumor RAS results was 90.4% (47/52), the negative agreement was 93.5% (43/46), and the overall agreement (concordance) was 91.8% (90/98). The high concordance of plasma and tissue results demonstrates that blood‐based RAS mutation testing is a viable alternative to tissue‐based RAS testing. Implementation of circulating tumor DNA testing in clinical practice has been hindered by the variable performance of available methods. Here, we demonstrate that plasma mutation testing using BEAMing as a standardized platform is comparable to tumor tissue testing and can be useful in the clinic to select patients with metastatic colorectal cancer for targeted therapy.

When the foot impacts the ground in running, large forces and loading rates can arise that may contribute to the development of overuse injuries. Investigating which biomechanical factors contribute to these impact loads and loading rates in running could assist clinicians in developing strategies to reduce these loads. Therefore, the goals of our work were to determine variables that predict the magnitude of the impact peak and loading rate during running, as well as to investigate how modulation of knee and hip muscle activity affects these variables. Instrumented gait analysis was conducted on 48 healthy subjects running at 3.3m/s on a treadmill. The top four predictors of loading rate and impact peak were determined using a stepwise multiple linear regression model. Forward dynamics was performed using a whole body musculoskeletal model to determine how increased muscle activity of the knee flexors, knee extensors, hip flexors, and hip extensors during swing altered the predictors of loading rate and impact peak. A smaller impact peak was associated with a larger downward acceleration of the foot, a higher positioned foot, and a decreased downward velocity of the shank at mid-swing while a lower loading rate was associated with a higher positioned thigh at mid-swing. Our results suggest that an alternative to forefoot striking may be increased hip flexor activity during swing to alter these mid-swing kinematics and ultimately decrease the leg's velocity at landing. The decreased velocity would decrease the downward momentum of the leg and hence require a smaller force at impact.

Hydrogen embrittlement (HE) poses the risk of premature failure for many metals, especially high-strength steels. Due to the utilization of hydrogen as an environmentally friendly energy source, efforts are made to improve the resistance to HE at elevated pressures and temperatures. In addition, applications in hydrogen environments might require specific material properties in terms of thermal and electrical conductivity, magnetic properties as well as corrosion resistance. In the present study, three high-strength Cu-base alloys (Alloy 25, PerforMet® and ToughMet® 3) as well as austenitic stainless AISI 321, Ni-base alloy IN 625 and ferritic steel 1.4511 are charged in pressurized hydrogen and subsequently tested by means of Slow Strain Rate Testing (SSRT). The results show that high-strength Cu-base alloys exhibit a great resistance to HE and could prove to be suitable for materials for a variety of hydrogen applications with rough conditions such as high pressure, elevated temperature and corrosive environments.

Researchers have postulated that reduced hip-abductor muscle strength may have a role in the progression of knee osteoarthritis by increasing the external knee-adduction moment. However, the relationship between hip-abductor strength and frontal-plane biomechanics remains unclear. To experimentally reduce hip-abduction strength and observe the subsequent changes in frontal-plane biomechanics. Descriptive laboratory study. Research laboratory. Eight healthy, recreationally active men (age = 27 ± 6 years, height = 1.75 ± 0.11 m, mass = 76.1 ± 10.0 kg). All participants underwent a superior gluteal nerve block injection to reduce the force output of the hip-abductor muscle group. Maximal isometric hip-abduction strength and gait biomechanical data were collected before and after the injections. Gait biomechanical variables collected during walking consisted of knee- and hip-adduction moments and impulses and the peak angles of contralateral pelvic drop, hip adduction, and ipsilateral trunk lean. Hip-abduction strength was reduced after the injection (P = .001) and remained lower than baseline values at the completion of the postinjection gait data collection (P = .02). No alterations in hip- or knee-adduction moments (hip: P = .11; knee: P = .52) or impulses (hip: P = .16; knee: P = .41) were found after the nerve block. Similarly, no changes in angular kinematics were observed for contralateral pelvic drop (P = .53), ipsilateral trunk lean (P = .78), or hip adduction (P = .48). A short-term reduction in hip-abductor strength was not associated with alterations in the frontal-plane gait biomechanics of young, healthy men. Further research is needed to determine whether a similar relationship is true in older adults with knee osteoarthritis.

Although approximately half of all metastatic colorectal cancers (mCRCs) harbour mutations in KRAS or NRAS , hardly any progress has been made regarding targeted treatment for this group over the last few years. Here, we investigated the efficacy of vertical inhibition of the RAS‐pathway by targeting epidermal growth factor receptor (EGFR) and mitogen‐activated protein kinase kinase (MEK) in patient‐derived xenograft (PDX) tumours with primary KRAS mutation. In total, 19 different PDX models comprising 127 tumours were tested. Responses were evaluated according to baseline tumour volume changes and graded as partial response (PR; ≤ − 30%), stable disease (SD; between −30% and +20%) or progressive disease (PD; ≥ + 20%). Vertical inhibition with trametinib and cetuximab induced SD or PR in 74% of analysed models, compared to 24% by monotherapy with trametinib. In cases of PR by vertical inhibition (47%), responses were lasting (as long as day 137), with a low incidence of secondary resistance (SR). Molecular analyses revealed that primary and SR was driven by transcriptional reprogramming activating the RAS pathway in a substantial fraction of tumours. Together, these preclinical data strongly support the translation of this combination therapy into clinical trials for CRC patients.