Phase Progression Research Articles

Cell-cycle phase progression analysis identifies three unique phenotypes in soft tissue sarcoma

PurposeLoddo et al. (Br J Cancer 100:959–70, 2009) established the prognostic significance of cell cycle markers and "Cell-Cycle Phenotypes" in breast carcinoma. This study aims to 1) identify prognostic cell-cycle markers in sarcoma, and 2) assess the prognostic potential of specific cell-cycle phenotypes in sarcoma.MethodsTissue samples from 128 soft tissue sarcomas were stained for four cell cycle-specific markers: Mcm2, Geminin, Plk1, and H3S10ph. Only primary soft tissue tumors (liposarcoma, leiomyosarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma) were included in the analysis. Any tumor coming from a recurrent or metastatic lesion were excluded from the analysis. Three cell-cycle phenotypes (I, II, III) were derived from marker expression patterns. Prognostic significance was evaluated in a subset of primary soft tissue sarcomas using Cox regression for survival analysis.ResultsCompared to phenotype I, the phenotype III tumors had a decreased 5-year overall survival (HR 6.81 [2.36–19.61]; p = < 0.001), 5-year disease-free survival (HR 1.07 (1.02–1.18); p = 0.004), and 5-year metastasis-free survival (HR 4.34 [1.58–11.93]; p = 0.004).High expression of Plk1 was associated with decreased 5-year overall survival (HR: 4.04 CI [1.21–6.67; p = 0.02) and 5-year metastasis-free survival (HR: 2.91 CI [1.15–7.37]; p = 0.03). Geminin was also found to have a decreased 5-year overall survival (HR:2.84 CI [1.21–6.67]; p = 0.02). No statistical difference in prognostication were noted between phenotypes and the AJCC system.ConclusionsWe identified three unique sarcoma cell cycle phenotypes that have prognostic significance. This performs similarly to the AJCC staging system.

Ischemic stroke as a presenting feature of promyelocytic blast phase in chronic myeloid leukemia - an uncommon presentation: a case report and literature review in the post imatinib era.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm (MPN characterized by reciprocal translocation in the ABL1 and BCR region of chromosomes 9 and 22 respectively. Progression to the blast phase in chronic myeloid leukemia results in a poorer prognosis. It can be of either myeloid, lymphoid or a mixed lineage. Progression to the promyelocytic blast phase is very rare, and there are no evidence-based guidelines for its management. Thrombosis in CML is not well defined. Thrombosis can be seen in patients with acute promyelocytic leukemia (APL) with venous thrombosis (VTE) being more common than arterial thrombosis. Ischemic stroke as the presenting feature of blast phase progression in CML is extremely rare. We report a case of CML who presented to us with acute ischemic stroke and subsequently was diagnosed as CML transformed to the promyelocytic blast phase. She was successfully treated with dasatinib along with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO).

Enhancing radiosensitivity in osteosarcoma via CDKN2C overexpression: A mechanism involving G1 phase arrest mediated by inhibition of CDK4 expression and Thr172 phosphorylation

BackgroundThe limited radiosensitivity of osteosarcoma poses a challenge in applying radiotherapy, necessitating the search for effective radiosensitizing targets. MethodsThe lentiviral vectors were employed to establish CDKN2C-overexpressing (CDKN2C-OE) and CDKN2C-negative control (CDKN2C-NC) HOS and U2OS osteosarcoma cells. Cells were treated with or without irradiation (IR) to assess radiosensitization via viability, proliferation, apoptosis, and cell cycle analysis. A mouse model with subcutaneous tumors from CDKN2C-OE and CDKN2C-NC HOS cells evaluated tumor growth post-IR. Immunohistochemical staining and Western blot analysis were conducted to confirm model establishment and explore mechanisms. ResultsCDKN2C-OE combined with IR inhibited cell viability and proliferation, promoting apoptosis in vitro and inhibiting tumor growth in vivo. CDKN2C-OE inhibited G1 phase progression post-IR by suppressing Cyclin-dependent kinase 4 (CDK4) expression and Thr172 phosphorylation, reducing retinoblastoma protein (RB) phosphorylation at Ser807/811. CDKN2C-OE did not primarily impact the cell cycle by regulating the expression of CDK6 and Cyclin D1. Furthermore, when CDKN2C-OE was combined with IR, the expression of BAX, Caspase-3, and its active cleavage product, cleaved Caspase-3, was upregulated. ConclusionsOur research results indicate that overexpression of CDKN2C enhances radiosensitivity in osteosarcoma through the induction of G1 phase arrest and subsequent apoptosis. G1 phase arrest is mediated by the suppression of CDK4 expression and Thr172 phosphorylation, which consequently affects the expression of phosphorylated RB at the Ser807/811 sites.

Experiencia didáctica para el estudio y valoración de la Arquitectura Vernácula guatemalteca

The didactic experience for the study and valoration of Guatemalan Vernacular Architecture consists of a series of academic activities in progressive phases, which introduce this type of architectura in danger of extinction to 4th grade students of architecture at the Rafael Landivar University, in the course: valoration of architecture and territory. Students are progressively immersed in the topic, from the bibliography to field visits, endingin the scale representation of an architectural model. This experience allows participant to learn about architecture, its compositional elements, its construction technique and materials, all whitin the framework of the appreciation of material and intangible cultural heritage. ILIA: Investigaciones Latinoamericanas en Ingeniería y Arquitectura, No. 01, 2024: 75-78.

A progressive phase multiple-injection locking technique for jitter suppression in voltage-controlled ring oscillator

ABSTRACT This paper presents a jitter reduction technique for a voltage-controlled ring oscillator (VCRO). This technique is useful in employing VCRO-based circuits like Analog to Digital Converter (ADC), Phase Locked Loop (PLL), and various time-based circuits whose performance is severely degraded by jitter accumulation, an inherent property of VCRO. In the proposed technique, a 1-bit time-to-digital converter (TDC) is used to extract information about jitter with a sensitivity of 4ps/bit. The rise in phase detector output bit leads VCRO to work in Progressive Phase Multi-Injection Locking (PPM-IL) mode until VCRO gets jitter-free. The proposed work is designed in SCL 180 nm CMOS technology at 1.8 V supply. After enabling the proposed technique, the RMS jitter reduces from 7.436 ps to 1.198ps for VCRO running at 63 MHz and consumes a total power of 1.112 mW.

Machine‐Learning Based Multi‐Layer Soil Moisture Forecasts—An Application Case Study of the Montana 2017 Flash Drought

AbstractSoil moisture (SM) is an essential climate variable, governing land‐atmosphere interactions, runoff generation, and vegetation growth and productivity. Timely forecasts of SM spatial distribution and vertical profiles are needed for early detection and prediction of potential droughts. However, previous studies have primarily concentrated on historical or near real‐time soil moisture mapping, with less effort devoted to the development and integration of soil moisture forecast components within drought assessment systems. A satellite‐driven machine‐learning approach was developed in this study to build complex relationships between diversified predictor data sets and in situ multi‐layer SM measurements from the Montana Mesonet, a regionally dense environmental station network in the US upper Missouri and Columbia basins. The resulting 30‐m daily SM predictions showed strong performance against in situ SM measurements from 4‐, 8‐ and 20‐inch soil layers, and with 1‐ to 2‐week forecast lead times (R &gt; 0.91; RMSE ≤ 0.047 cm3/cm3). The machine‐learning model was subsequently applied to the entire Montana region, and the SM deficit forecasts with both 1‐ and 2‐week lead times successfully depicted onset, progression, and termination phases of the 2017 Montana flash drought, which was not effectively identified from prevailing operational systems. The resulting system is capable of delineating local scale SM heterogeneity, and could be extended to predict other critical water cycle variables, potentially enhancing future drought forecasts through multivariate assessments and benefiting water resource management, agricultural practices, and the provision of ecosystem services.

Aurorally Driven Supersonic Gravity Waves in Saturn's Atmosphere

AbstractSimulations with the Saturn Thermosphere‐Ionosphere General Circulation Model have revealed global‐scale gravity waves in Saturn's upper atmosphere that have not been observed or predicted before. They are forced by diurnally varying zonally non‐uniform distributions of Joule heating and ion drag at the high‐latitude auroral regions in both hemispheres and propagate outward from the source region. The supersonic zonal phase speed imposed by Saturn's rotation and the subsonic meridional phase velocity of about 800 m form a distinct spiral wave structure. They exhibit features of gravity waves: vertical phase progression opposite to the propagation of wave energy and long vertical wavelengths consistent with the dispersion relation for gravity waves. The amplitudes of the perturbations grow with height, reaching 6%–10% for relative temperature variations and up to 350 m for the meridional velocity perturbations. The main effect of these waves is to accelerate the retrograde westerly jets.

Phases of Progression: Students’ meaning-making of Epigenetic Visual Representations within and between Levels of Organization

AbstractThis study investigates the progression of students’ meaning-making of epigenetic phenomena while discussing multiple visual representations depicted at different levels of biological organization. Semi-structured focus group sessions involving ninth-grade students (aged 15-16) from a Swedish lower secondary school were video recorded. Students’ meaning-making with regard to form, function and transfer of scientific ideas was explored by analyzing students’ physical pointing and verbal utterances while interacting with and discussing the epigenetic visual representations. The study uncovered four phases of progression in students’ meaning-making. In phase 1, students’ focus is on unpacking scientific ideas within a single representation. In phase 2, students apply and transfer scientific ideas between different visual representations at the same organizational level. In phase 3, their meaning-making develops into linking between various levels of organization. Here, downward linking, from higher to lower levels, relies on form descriptions that limit the transfer of scientific ideas. In contrast, upward linking, from lower to higher organizational levels, relies on both descriptions of form and functional explanations, which facilitates the transfer of scientific ideas. Finally, in Phase 4, and manifested as “yo-yo reasoning”, students engage in a dynamic and repeated process of downward and upward linking that expresses a coherent understanding of epigenetics. The study findings underscore the significance of recognizing progression phases in facilitating students’ meaning-making of multiple representations of epigenetic phenomena. Future research could expand on these insights by investigating students’ meaning-making across other science education domains.

Effects of Pelvic Rocking and Deep Breathing Relaxation Exercises on the Progression of the Active Phase of the First Stage of Labor

Prolonged labor or undeveloped labor is one of the complications in childbirth. Where prolonged labor is labor that lasts more than 24 hours in primi and more than 18 hours in multi. The purpose of this research is for the Influence of Pelvic Rocking Exercise and Slow Deep Breathing Relaxation on the Progress of the First Stage of Labor among mothers giving birth in Indonesia in 2024. Research methods This is a pre experimental quantitative research with a group compilation statistical design. The data analysis used is univariate and bivariate analysis using the Mann Whitney hypothesis test, which is a non-parametric test that measures differences equivalent to the independent T test in parametric measurements. The p-value result was 0.000. This shows that there is a significant influence of pelvic rocking exercise and slow deep breathing relaxation on the progress of the first stage of labor in 2024. This pelvic rocking exercise and slow deep breathing relaxation intervention can be applied by the birthing mother so that the mother can give birth safely, comfortably and in a quicker time than without intervention.

Investigation of phytotoxic effects of fullerene С60 with the use of Allium-test

Aim. To investigate the cytogenetic effects of water-soluble fullerene C60 with the use of Allium test. To study the influence of various concentrations of fullerene С60 on the morpho-physiological parameters of A. cepa. Methods. The influence of different concentrations of fullerene С60 (25–100 μg/ml) on the induction of root formation and their growth, as well as its cytogenetic effects on the meristematic cells of root apices, were investigated. Results. It was found that fullerene C60 at concentrations of 50 and 75 μg/ml induced root formation and stimulated root growth, though causing minor deformations. Also, it was shown that fullerene С60 disrupts the progression of various phases of mitosis in the meristematic cells of roots, along with the occurrence of chromosomal aberrations at all investigated concentrations. Conclusions. The cytogenetic effects of water-soluble fullerene C60 were investigated for the first time using the Allium-test. Both positive effects on the morphophysiological parameters of A. cepa and its genotoxicity were demonstrated, which could indicate the disruptions in the mechanisms of spindle formation.

Phagocyte dynamics in the blastogenetic cycle of the colonial ascidian Botryllus schlosseri: Cell senescence, segregation and clearance after efferocytosis

In the colonial ascidian Botryllus schlosseri, phagocytes are involved in the clearance of apoptotic cells and corpses during the periodical generation changes or takeovers (TOs) that assure the renewal of the colonial zooids. The persistent respiratory burst associated with efferocytosis, leads to the induction of senescence. Indeed, giant, senescent phagocytes are abundant in the colonial circulation at TO, whereas, in the other phases of the colonial blastogenetic cycle, they colonise the ventral islands (VIs), a series of mesenchymal niches located in the lateral lacunae of the mantle, on both sides of the subendostylar sinus. VI phagocytes produce reactive oxygen species probably as a consequence of the massive phagocytosis of effete cells. VIs are progressively dismantled with the progress of the blastogenetic phases and phagocytes are released in the peribranchial chamber via transepithelial expulsion to be definitely expelled with the outflowing water through the cloacal siphon.

Cell cycle regulated expression of the WHI7 Start repressor gene

ABSTRACT Periodic transcriptional waves along the cell cycle ensure the accurate progression of the different cell cycle phases through the timely regulated expression of cell cycle proteins. The G1/S transition (Start) consists in the activation of a transcriptional program by G1 CDKs through the inactivation of Start transcriptional repressors, Whi5 and Whi7 in yeast or Rb in mammals. Here, we provide a comprehensive characterization of the transcriptional regulation of the Start repressor Whi7 in budding yeast. We found that WHI7 is a cell cycle regulated gene that shows periodic expression peaking in G1. Our results demonstrate that the three cell cycle transcriptional programs related to G1 and their corresponding transcription factors are involved in the transcriptional control of WHI7. Specifically, we identified that the transcriptional regulators Swi5 and Mcm1-Yox1, which are involved in late M and early G1 expression, and the transcription factors MBF and SBF, which are responsible for G1/S expression, are able to associate and regulate the WHI7 gene. In summary, in this work, we provide new mechanisms for the regulation of the Start repressor Whi7, which highlights the precise and complex control of the cell cycle machinery governing the G1/S transition.

Anomaly inflow for dipole symmetry and higher form foliated field theories

In accordance with recent progress of fracton topological phases, unusual topological phases of matter hosting fractionalized quasiparticle excitations with mobility constraints, new type of symmetry is studied — multipole symmetry, associated with conservation of multipoles. Based on algebraic relation between dipole and global charges, we introduce a series of (d + 1)-dimensional BF theories with p-form gauge fields, which admit dipole of spatially extended excitations, and study their physical properties. We elucidate that gauge invariant loops have unusual form, containing linear function of the spatial coordinate, which leads to the position dependent braiding statistics and unusual ground state degeneracy dependence on the system size. We also show that the theories exhibit a mixed ’t Hooft anomaly between p-form and (d − p)-form dipole symmetries, which is canceled by an invertible theory defined in one dimensional higher via anomaly inflow mechanism.

In situ Synchrotron X-ray Metrology Boosted by Automated Data Analysis for Real-time Monitoring of Cathode Calcination.

Synchrotron X-ray-based in situ metrology is advantageous for monitoring the synthesis of battery materials, offering high throughput, high spatial and temporal resolution, and chemical sensitivity. However, the rapid generation of massive data poses a challenge to on-site, on-the-fly analysis needed for real-time process monitoring. Here, a weighted lagged cross-correlation (WLCC) similarity approach is presented for automated data analysis, which merges with in situ synchrotron X-ray diffraction metrology to monitor the calcination process of the archetypal nickel-based cathode, LiNiO2. The WLCC approach, incorporating variables that account for peak shifts and width changes associated with structural transformations, enables rapid extraction of phase progression within 10 seconds from tens of diffraction patterns. Details are captured, from initial precursors to intermediates and the final layered LiNiO2, providing information for agile on-site adjustments during experiments and complementing post hoc diffraction analysis by offering insights into early-stage phase nucleation and growth. Expanding this data-powered platform paves the way for real time calcination process monitoring and control, which is pivotal to quality control in battery cathode manufacturing.

Dynamics of apex and leaf development in barley as affected by PPD-H1 alleles in two contrasting PHYC backgrounds under short or long photoperiod.

Barley development from seedling to flowering involves both external and internal changes, the latter requiring microscopic observation. Internal changes allow for the classification of preflowering development into three phases: vegetative, early reproductive, and late reproductive. Genetic and environmental factors influence the duration of these phases, impacting grain yield. Photoperiod-sensitivity genes PPD-H1 play a major role in flowering time, affecting adaptation; however, the effect might also be direct (beyond affecting phenology). In this paper, we aimed to assess how PPD-H1 alleles affect barley development, including the progression of growth phases, leaf emergence, tillering dynamics, and spikelet development. Two experiments (field and controlled conditions) were conducted with a factorial combination of (i) four near-isogenic lines (NILs) for PPD-H1 alleles (ppd-H1 or Ppd-H1) under two contrasting PHYC genetic backgrounds (PhyC-l and PhyC-e) and (ii) two photoperiod conditions (short and long days). As expected, longer photoperiods led to a shorter growth cycle. All subphases of time to flowering, final leaf number, and phyllochron were affected by photoperiod. The effects of PPD-H1 on flowering time depended on the PHYC genetic backgrounds and photoperiod conditions. PPD-H1 effects on flowering time were associated with leaf number and phyllochron; the interplay between leaf number and phyllochron affected mainly the late reproductive phase. We also found that although PPD-H1 did not affect the phyllochron of the first six leaves, the phyllochron of leaves appearing later, when grown under a short photoperiod, was consistently increased in lines carrying the ppd-H1 allele. Tillering dynamics exhibited variability, but PPD-H1 did not affect the final spike number under a 24-h photoperiod.

Revealing the degradation pathways of layered Li-rich oxide cathodes.

Layered lithium-rich transition metal oxides are promising cathode candidates for high-energy-density lithium batteries due to the redox contributions from transition metal cations and oxygen anions. However, their practical application is hindered by gradual capacity fading and voltage decay. Although oxygen loss and phase transformation are recognized as primary factors, the structural deterioration, chemical rearrangement, kinetic and thermodynamic effects remain unclear. Here we integrate analysis of morphological, structural and oxidation state evolution from individual atoms to secondary particles. By performing nanoscale to microscale characterizations, distinct structural change pathways associated with intraparticle heterogeneous reactions are identified. The high level of oxygen defects formed throughout the particle by slow electrochemical activation triggers progressive phase transformation and the formation of nanovoids. Ultrafast lithium (de)intercalation leads to oxygen-distortion-dominated lattice displacement, transition metal ion dissolution and lithium site variation. These inhomogeneous and irreversible structural changes are responsible for the low initial Coulombic efficiency, and ongoing particle cracking and expansion in the subsequent cycles.

Reflection of Storm Surge and Tides in Convergent Estuaries With Dams, the Case of Charleston, USA

AbstractConvergent estuaries have been shortened by dam‐like structures worldwide. Here, we evaluate 31 long‐term water level stations and use a semi‐analytical tide model to investigate how landward‐funneling and a dam influence tidal and storm surge propagation in the greater Charleston Harbor region, South Carolina, where three rivers meet: the Ashley, Cooper, and Wando. Results show that the phase speed and amplification of the principal tidal harmonic (M2) is larger than other long waves such as storm surge (∼1–4 days) and setup‐setdown (∼4–10 days). Further landward, all waves attenuate, but, as they approach the dam on the Cooper River, a frequency dependent response in amplitude and phase progression occurs. A semi‐analytical tidal model shows that funneling and the presence of a dam amplify tidal waves through wave interference from partial and full reflection, respectively. The different phase progressions of the reflected waves interact with the incident wave to increase or decrease the summed overall wave amplitude. Using a friction‐convergence parameter space, we demonstrate that dominant tides in 23 estuaries and the tidal, storm surge, and setup‐setdown waves in the Cooper River can be delineated into three regimes that describe landward amplification or attenuation associated with funneling, a dam, or both. The regime of each tidal constituent is consistent but can change with the duration and height of each storm surge event; dam associated wave interference can attenuate long‐duration events, while the most intense events (short duration, high water) are amplified by dams more than funneling and greatly increase flood exposure.

Precise Fourier parameters of Cepheid radial velocity curves: Towards refining the Hertzsprung progression models

Context. Radial velocity (RV) curves of Classical Cepheids allow precise determination of the resonant periods, which in turn help to constrain fundamental parameters of these stars. The RV curves of Cepheids are also useful for identifying their pulsation modes and for distance determination using the parallax-of-pulsation method. Aims. The primary goal of this paper is to derive precise Fourier parameters of the RV curves for fundamental and first-overtone Galactic Cepheids. Our secondary objectives are then to analyze the progression of the Fourier parameters up to the seventh harmonic, and to propose an identification of the pulsation modes of the stars. Methods. For each star, we carefully selected RV measurements available in the literature that yield the highest precision of Fourier parameters according to the procedure that follows. We performed a Fourier decomposition of the RV curves using the unweighted least-square method and the standard deviation of the fit was used to derive the uncertainty on the Fourier parameters. We corrected for zero-point differences between datasets and RV modulations caused by binary motion. Results. With this study we have more than doubled the number of Cepheids with published RV curve Fourier parameters and with their uncertainty properly estimated. Our sample includes 178 fundamental-mode and 33 first-overtone pulsators, as well as 7 additional Cepheids whose pulsation mode is uncertain or undetermined according to our criteria. For the fundamental-mode Cepheids, the precision of the obtained low-order Fourier phases and amplitudes is about seven times and 25% better, respectively, as compared to the precision achieved in previously published Fourier parameter surveys. With highly accurate RV Fourier phases ϕ21, we are able to firmly identify V495 Cyg as a new first-overtone Cepheid and we confirm the first-overtone nature of several other stars. In particular, α UMi should be firmly classified as a first-overtone pulsator. In three objects (VY Per, AQ Pup, and QZ Nor), we find significant γ-velocity variations, which for the first two objects (and possibly for QZ Nor as well) can be attributed to the spectroscopic binarity of these stars. Finally, the analysis of the fundamental mode Fourier parameters up to seventh order reveals tight progression of Fourier phases for all pulsation periods. Conclusions. We provide new precise Fourier parameters of Cepheid RV curves determined from RV measurements available in the literature together with unpublished data. The pulsation period coverage and the precision obtained, in particular for Fourier phase ϕ21, will be useful for studying the dynamics of Cepheid pulsations with the help of hydrodynamical models. Further RV measurements from modern high-resolution spectroscopic instruments will be important to improve these results.

Rate of cervical dilatation and duration of active phase of labor among low-risk pregnant women delivering at Dodoma regional referral hospital

Background: Cervical dilation at the onset of the active phase of labor determines the rate of cervical dilatation and the duration of the active phase of labor. Identifying the abnormality toward the natural progress of the active phase of labor is important because timely intervention has been observed to be controversial among developing countries during the current practice among health care providers due to different opinion on the onset of the active phase. Thus, indication like poor progress of labor has been poorly explained in which it has become a common indication for a steady increased rate of primary cesarean section and increased new born morbidity due to birth asphyxia. Objective: This study aimed at determining the rate of cervical dilatation and duration of active phase of labor among low-risk pregnant women delivered at Dodoma Regional Referral Hospital. Methods: This is a hospital-based prospective cross-sectional study where systematic sampling method was employed in obtaining sample of 300 pregnant women. Local partograph and a semi structured questionnaire were used to record the information and findings. Data were analyzed using SPSS version 25. One sample t-test was used to determine and compare the rate and duration of active labor with the WHO standard rate. P value &lt; 0.05 was considered statistically significant. Results: The mean rate of cervical dilatation during active phase for nulliparous was 0.81cm/hour and multiparous was 0.89cm/hour respectively, which is observed to be slower than standard WHO rates. The duration of the active phase of labor was 7.6 hours for nulliparous and 6.8 hours for multiparous. Conclusion: The rate of cervical dilatation was much slower hence the longer duration of active phase in both groups than the WHO standards.

Mechanisms of fatigue degradation process in axially loaded grouted connections under submerged conditions

Grouted connections in offshore support structures bond overlapping steel tubes using ultra-high strength grout. These connections, used in jacket structures, face dynamic pulsating loads and submerged conditions. Current design guidelines offer simplified S-N curves that do not reflect realistic conditions for offshore wind turbines. This study introduces a new S-N curve for axially loaded grouted connections under submerged conditions, based on large-scale high-cycle fatigue experiments. It also analyses the degradation behaviour of cyclic axially loaded grouted connections to identify critical phase changes: stable, incremental, and progressive. The study examines the impact of different load levels on degradation, focusing on displacement between the pile and sleeve. Lower load levels result in longer stable and progressive phases. As load levels increase, the stable phase shortens and eventually disappears at the highest load levels. Damage within the grout material is categorised into crack-driven and crushing-driven patterns, with the latter linked to longer lifetimes. Even at the lowest load levels, minor damage occurs, precluding an endurance limit. This understanding of degradation mechanisms supports the assessment of grouted connections using monitoring systems.