Longitudinal Growth Research Articles

Quantitative Assessment of Drug Efficacy and Emergence of Resistance in Patients with Metastatic Renal Cell Carcinoma Using a Longitudinal Exposure-Tumor Growth Inhibition Model: Apitolisib (Dual PI3K/mTORC1/2 Inhibitor) Versus Everolimus (mTORC1 Inhibitor).

Cancer remains a significant global health challenge, and despite remarkable advancements in therapeutic strategies, poor tolerability of drugs (causing dose reduction/interruptions) and/or the emergence of drug resistance are major obstacles to successful treatment outcomes. Metastatic renal cell carcinoma (mRCC) accounts for 2% of global cancer diagnoses and deaths. Despite the initial success of targeted therapies in mRCC, challenges remain to overcome drug resistance that limits the long-term efficacy of these treatments. Our analysis aim was to develop a semi-mechanistic longitudinal exposure-tumor growth inhibition model for patients with mRCC to characterize and compare everolimus (mTORC1) and apitolisib's (dual PI3K/mTORC1/2) ability to inhibit tumor growth, and quantitate each drug's efficacy decay caused by emergence of tumor resistance over time. Model-estimated on-treatment tumor growth rate constant was 1.7-fold higher for apitolisib compared to everolimus. Estimated half-life for loss of treatment effect over time for everolimus was 16.1 weeks compared to 7.72 weeks for apitolisib, suggesting a faster rate of tumor re-growth for apitolisib patients likely due to the emergence of resistance. Goodness-of-fit plots including visual predictive check indicated a good model fit and the model was able to capture individual tumor size-time profiles. Based on our knowledge, this is the first clinical report to quantitatively assess everolimus (mTORC1) and apitolisib (PI3K/mTORC1/2) efficacy decay in patients with mRCC. These results highlight the difference in overall efficacy of 2 drugs due to the quantified efficacy decay caused by emergence of resistance, and emphasize the importance of model-informed drug development for targeted cancer therapy.

Impact of childhood nephrotic syndrome on obesity and growth: a prospective cohort study.

Children with nephrotic syndrome are at risk of obesity and growth impairment from repeated steroid treatment. However, incidence and risk factors for obesity and short stature remain uncertain, which is a barrier to preventative care. Our aim was to determine risk, timing, and predictors of obesity and short stature among children with nephrotic syndrome. We evaluated obesity and longitudinal growth among children (1-18years) enrolled in Insight into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics. We included children with nephrotic syndrome diagnosed between 1996-2019 from the Greater Toronto Area, Canada, excluding congenital or secondary nephrotic syndrome. Primary outcomes were obesity (body mass index Z-score ≥ + 2) and short stature (height Z-score ≤ -2). We evaluated prevalence of obesity and short stature at enrolment (< 1-year from diagnosis) and incidence during follow-up. Cox proportional hazards models determined the association between nephrotic syndrome classification and new-onset obesity and short stature. We included 531 children with nephrotic syndrome (30% frequently relapsing by 1-year). At enrolment, obesity prevalence was 23.5%, 51.8% were overweight, and 4.9% had short stature. Cumulative incidence of new-onset obesity and short stature over median 4.1-year follow-up was 17.7% and 3.3% respectively. Children with frequently relapsing or steroid dependent nephrotic syndrome within 1-year of diagnosis were at increased risk of new-onset short stature (unadjusted hazard ratio 3.99, 95%CI 1.26-12.62) but not obesity (adjusted hazard ratio 1.56, 95%CI 0.95-2.56). Children with ≥ 7 and ≥ 15 total relapses were more likely to develop obesity and short stature, respectively. Obesity is common among children with nephrotic syndrome early after diagnosis. Although short stature was uncommon overall, children with frequently relapsing or steroid dependent disease are at increased risk of developing short stature. Effective relapse prevention may reduce steroid toxicity and the risk of developing obesity or short stature.

Growth after pediatric kidney transplantation: a 25-year study in a pediatric kidney transplant center.

Growth failure is one of the major complications of pediatric chronic kidney disease. Even after a kidney transplant (KT), up to 50 % of patients fail to achieve the expected final height. This study aimed to assess longitudinal growth after KT and identify factors influencing it. A retrospective observational study was performed. We reviewed the clinical records of all patients who underwent KT for 25 years in a single center (n=149) and performed telephone interviews. Height-for-age and body mass index (BMI)-for-age were examined at KT, 3months, 6months, 1 year, and 5 years post-transplant and at the transition to adult care. We evaluated target height, disease duration before KT, need and type of dialysis, recombinant human growth hormone pretransplant use, nutritional support, glomerular filtration rate (GFR), and cumulative corticosteroid dose. At transplant, the average height z-score was-1.38, and height z-scores showed catch-up growth at 6months (z-score-1.26, p=0.006), 1 year (z-score-1.15, p<0.001), 5 years after KT (z-score-1.08, p<0.001), and on transition to adult care (z-score-1.22, p=0.012). Regarding BMI z-scores, a significant increase was also detected at all time points (p<0.001). After KT, GFR was significantly associated with height z-score (p=0.006) and BMI z-score (p=0.006). The height in transition to adult care was-1.28 SD compared to the target height. Despite the encouraging results regarding catch-up growth after KT in this cohort, results remain far from optimum, with a lower-than-expected height at the time of transition.

Sex-specific effects of environmental temperature during gestation on fluctuating asymmetry in deciduous teeth.

External environmental heat exposure during gestation impacts the physiology of human development in utero, but evidence for these impacts has not yet been explored in dentition. We examined deciduous teeth for fluctuating asymmetry (FA), a measure of developmental instability, together with gestational environmental temperature data drawn from historical weather statistics. We measured dental casts from the longitudinal Burlington Growth Study, representing 172 participants (ages 3-6 years) with health records. FA was calculated from crown dimensions and intercuspal distances that develop during gestation. Multiple regression separated by sex (nfemale = 81) examined the effects of mean temperatures in each trimester, controlling for birth year. In females, increased temperatures during the first trimester are significantly associated with an increase in FA (p = 0.03), specifically during the second and third prenatal months (p = 0.03). There is no relationship between temperature and FA for either sex in the second or third trimesters, when enamel is formed. Dental instability may be sensitive to temperature in the first trimester in females during the scaffolding of crown shape and size in the earliest stages of tooth formation. Sexual dimorphism in growth investment strategies may explain the differences in results between males and females. Using enduring dental characteristics, these results advance our understanding of the effects of temperature on fetal physiology within a discrete period.

Mapping carbon nanotube aspect ratio, concentration and spinning in FCCVD synthesis controlled by sulphur

Floating catalyst chemical vapor deposition (FCCVD) enables ultrafast synthesis of CNTs and other 1D nanoparticles and their direct assembly as macroscopic solids. The chalcogen growth promotor in FCCVD produces high aspect ratio CNTs that can aggregate in the gas phase and form an aerogel which can be continuously spun as macroscopic fibres or sheets. We study the role of sulphur in controlling CNT morphology and aggregation by synthesising CNTs under a wide range of S/C ratios (0.001 to 5 wt.%) and determining their diameter and length distributions, number concentration and form of aggregation. Increasing S/C ratio in this range increases mean number of CNT walls from 1 to 8, decreases mean length from 34 to 6 µm, but CNT number concentration remains approximately constant at 8 × 108#/cm3. Assuming growth within the first 3 cm of the reactor, longitudinal growth rate spans 1.5- 6.5 µm/s for the different CNT morphologies, but with similar mass throughput of 700 attogram/catalyst. This indicates the amount of carbon reaching the catalyst and solidifying as CNT remains constant regardless of the sulphur available in the catalyst, suggesting the rate limiting process is not at the catalyst/promoter interface but instead in the transport of carbonaceous active precursors to the catalyst, either due to their diffusion in the gas phase or decomposition kinetics. The CNTs produced range from polymer-like, which readily bundle and form aerogels, to rod-like that do not. We include aerogelation “phase diagrams” for different CNT concentrations, aspect ratios and CNT bending stiffness.

Age-related changes in densitometry and histomorphometry of long bone during the pubertal growth spurt in male rats.

Because experimental studies to determine the developmental toxicity of exposure to various substances in children are impossible, many studies use immature male rats. This study aimed to provide normative data for longitudinal bone growth with age during the puberty in male rats. In order to evaluate long bone growth and mineralization we examined bone size and bone density by dual-energy X-ray absorptiometry, analyzed histomorphometry of the growth plate, and serum hormone levels relevant to bone growth from postnatal day (PD)20 to PD60. The length and weight of long bones increased strongly by PD40, and no further increase was observed after PD50. On the other hand, tibial growth plate height decreased sharply after PD50 along with a reduction in the number of cells and columns, which was probably responsible for the absence of further lengthening of long bones. Parameters related to bone formation such as bone area ratio, and the thickness and number of trabeculae, also increased significantly between PD40 and PD50. Furthermore, serum levels of IGF-1 peaked at PD30 and testosterone increased rapidly on and after PD40, when IGF-1 levels were going down. These changes may participate in the parallel increase in mineral acquisition, as well as lengthening of long bones. Our findings provide comprehensive data for changes in bone density, histomorphometry of long bones, and hormone levels relevant to bone growth during the growth spurt. This will be useful for planning animal toxicological studies, particularly for deciding on the appropriate age of animals to use in given experiments.

Associations between life course longitudinal growth and hip shapes at ages 60–64 years: evidence from the MRC National Survey of Health and Development

ObjectiveWe sought to examine associations between height gain across childhood and adolescence with hip shape in individuals aged 60–64 years from the Medical Research Council National Survey of Health and...

Single‐Source Evaporated High‐Quality Single‐Phase Cs3Cu2I5 Scintillator Films for High Performance X‐Ray Imaging

AbstractVacuum‐evaporated metal halides (MHs) scintillator thick films have received much attention in the X‐ray imaging field due to their excellent light yield and uniform large‐area preparation. However, the inevitable heteromorphic homologs in MHs (e.g., Copper‐based MHs (Cu‐MHs): CsCu2X3∖Cs3Cu2X5) and change of film structural backbone will result in spectral hybridization (phase purity), and the film eventually detaches (lattice mismatches). Herein, a single‐source vacuum evaporation method to prepare a thick film (≈10 µm) of Cu‐MHs (as an example) scintillators is realized: 1) Presynthesis of pure phase materials by solution method with a protective agent to ensure phase purity without precise control of component ratios in evaporation process; 2) One‐shot formation of film structural backbone avoids stress accumulation and utilize the longitudinal growth characteristics of crystalline films to obtain crystal orientations with better optical outputs. Finally, the films obtained have a light yield comparable to a partially single‐crystal (53 983 photons MeV−1) and an imaging resolution (14.1 lp mm−1) comparable to the partial template method. The detection system based on the prepared Cu‐MHs scintillator thick films exhibits good response speed and linearity in response to different X‐ray radiation intensities and exposure times. The method will further drive the application of MHs is believed.

Unveiling the Regulatory Role of miRNAs in Internode Elongation: Integrated Analysis of MicroRNA and mRNA Expression Profiles across Diverse Dwarfing Treatments in Maize (Zea mays L.).

MicroRNAs are crucial regulators of gene expression in maize. However, the mechanisms through which miRNAs control internode elongation remain poorly understood. This study engineered varying levels of internode elongation inhibition, revealing that dwarfing treatments diminished gibberellin levels, curtailed cell longitudinal growth, and slowed the rate of internode elongation. Comprehensive transcriptome and miRNA profiling of the internode elongation zone showed gene expression changes that paralleled the extent of the internode length reduction. We identified 543 genes and 29 miRNAs with significant correlations to internode length, predominantly within families, including miR164 and miR396. By incorporating target gene expression levels, we pinpointed nine miRNA-mRNA pairs that are significantly associated with the regulation of the internode elongation. The inhibitory effects of these miRNAs on their target genes were confirmed through dual-luciferase reporter assays. Overexpression of miR164h in maize resulted in increased internode and cell length, suggesting a novel genetic avenue for manipulating plant stature. These miRNAs may also serve as precise spatiotemporal regulators for in vitro plant development.

Early history of the study of bone growth (1722–1875)

IntroductionBone growth is a fascinating process, primarily due to its complexity. Equally engaging is the history of its study, which, however, remains unknown to most anatomists and surgeons.Materials and methodsA literature search was performed in original publications and historical sources.ResultsThe early history of bone growth study may be divided into two periods. Firstly, the experimental one, between 1722 and 1847, which consisted in the study of bone growth by the drilling of benchmark holes into the diaphysis, and examination of growing bones in madder-fed animals. In the course of one century, four French scientists (Henri-Louis Duhamel du Monceau, Marie-Jean-Pierre Flourens, Gaspard Auguste Brullé and Frédéric Léopold Hugueny) and one British researcher (John Hunter) proved experimentally that the longitudinal growth of long bones occurred only at its epiphyseal ends and their final shape resulted from apposition and resorption processes taking place simultaneously both on the periosteal and intramedullary surfaces of the bone. In the second, the microscopic period (1836–1875), the physeal growth cartilage was discovered and described in detail, including its importance for the longitudinal growth of long bones. The first description of growth cartilage was published by a Swiss anatomist Miescher in 1836. Subsequently, this structure was studied by a number of English, German and French anatomists and surgeons. This whole period was concluded by Alfred Kölliker´s extensive study of bone resorption and its significance for typical bone shapes and Karl Langer´s study of the vascular supply of the growing and mature bone.ConclusionResearch by French, English, German and Swiss scientists between 1727 and 1875 yielded fundamental insights into the growth of long bones, most of which are still valid today.

Abstract 7537: “Cross-over Effect” in survival curves with immune-checkpoint inhibition: Identifying ideal candidates for immunotherapy-only approaches in specific tumor histologies

Abstract Immune checkpoint inhibition (ICI), a cornerstone of modern immunotherapy (IO), has revolutionized cancer treatment, offering significant survival benefits across various malignancies. Initial trials with ICI in refractory cancers demonstrated remarkable efficacy compared to standard-of-care (SOC) treatments. With the integration of ICI into combination therapies, including chemotherapy and multi-tyrosine kinase inhibitors (TKI), its role in frontline, early-stage, and locally advanced cancers has grown. However, the potential of an immunotherapy-only strategy, especially in advanced malignancies, warrants better biomarker selected approaches given the inconsistencies with existing biomarkers. This study investigates the "cross-over” effect observed in Kaplan-Meier survival curves from randomized trials comparing ICI with non-ICI agents where the survival curves, assumed to be proportionally constant distinctly cross over each other during the on-treatment monitoring period. We initiated a meta-analysis investigating randomized trials comparing ICIs with non-ICI historical SOC agents and finally analyzed data from 38 large clinical trials. Trials were selected based on their comparative nature with overall survival (OS) and progression-free survival (PFS) data as outcomes. A positive “cross-over” in Kaplan-Meier curves was identified when divergence occurred for at least three consecutive months. Cross-over in PFS and OS curves were observed in 53% (20/38) and 43% (16/37) of trials, respectively. All cross-overs were one-sided with the ICI arm crossing over the non-ICI arm with a superior tail. Notably, 100% of trials with OS curve cross-over involved ICIs against chemotherapy. A significant association (Fischer’s exact test, p=0.01) was found between OS curve cross-over and adenocarcinoma histologies, in contrast to trials with no cross-over effect, predominantly featuring squamous cell carcinomas. This pattern persisted within various organ sites such as the lung, esophagus, and cervix where both adenocarcinomas and squamous histological patterns are seen. Cross-over of Kaplan-Meier curves blatantly violates the cox-proportional hazard assumption, potentially underestimating the impact of the ICI-only approach compared to alternative therapies. These observations highlight substantial biological heterogeneity in tumor responses to ICI versus chemotherapy. The cross-over effect, particularly pronounced in gland-forming tumors (adenocarcinomas), underscores the urgent need to investigate mechanisms of ICI resistance in these tumor types and incorporate tumor histology and longitudinal tumor growth dynamics into existing predictive models for biomarkers for IO response and help identify patients who would benefit the most from immunotherapy-only approaches. Citation Format: Shubhank Goyal, Anish Thomas, Parth Anil Desai. “Cross-over Effect” in survival curves with immune-checkpoint inhibition: Identifying ideal candidates for immunotherapy-only approaches in specific tumor histologies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7537.

Tailoring ZnO nanorods for efficient photocatalytic production of H2O2 from water without sacrificial agents: A study on length optimization

In this study, we investigated the optimal length of zinc oxide nanorods (ZnO NRs) for the production of photocatalytic hydrogen peroxide (H2O2) using a hydrothermal method at 150 °C with reaction times ranging from 2 to 12 h. The study found that the size of the crystals increased when the reaction duration was extended, resulting in an increase in the size from 26 to 48 nm. SEM measurements indicated that ZnO exhibited longitudinal growth along the c-axis, increasing the nanorod length from 1 μm to 3.5 μm. The bandgaps of the ZnO NRs were between 3.21 and 3.25 eV. The optimal conditions for H2O2 production were identified to be 10 min of sonication and 15 min of UV illumination. The generation of H2O2 increased with the dosage of ZnO, ranging from 0.01 to 0.3 g/20 ml. The highest H2O2 production was attained by employing ZnO NRs at 1.6 μm in length with 49 mgL−1 Under UV irradiation and 28 mgL−1 under sonication irradiation. This study offers new perspectives for the design and production of H2O2 using ZnO NRs of a certain length, which may be beneficial for environmental remediation and energy generation.

Abstract 5719: Targeting CDK4/6 and BET proteins for the treatment of RB+ and RB- osteosarcoma

Abstract Osteosarcoma (OS) is the most common malignant bone cancer characterized by heterogeneity and genomic instability. Treatment and survival of patients have not improved in several decades, making it urgent to develop safe and effective therapies. Dysregulation of cell cycle regulators CDKN2A, cyclins, and CDK4/6 represent high-risk signatures in aggressive OS and can be targeted via CDK4/6 inhibitors (CDK4/6i). However, monotherapy often fails due to resistance from speculated RB loss as well as hyperactivation of compensatory signaling pathways in RB proficient cancers. In addition, &amp;gt;70% of OS patients have RB loss which is viewed as a biomarker of therapeutic response that negates the use of CDK4/6i. However, more research is needed in RB-deficient preclinical models to clearly define and validate the utility of RB as a biomarker for patient stratification. Based on our screening data, we hypothesize that combining CDK4/6i with bromodomain and extraterminal domain inhibitors (BETi) will potentiate anti-tumorigenic effects regardless of RB status in OS. BETi creates imbalances between transcription and replication which worsens oncogenic stress. In OS cell lines, combination index and Bliss analysis indicated additive-to-synergistic growth inhibition using CDK4/6i (abemaciclib or palbociclib) and BETi (AZD5153). Dual therapy also resulted in increased apoptosis at clinically relevant concentrations in an OS xenoline (TT2) compared to monotherapy. To determine potential for emergence of therapeutic resistance, an in-vitro longitudinal growth delay assay was established. While single agent therapies resulted in transient decreases in cell numbers over time, combination CDK4/6i+BETi resulted in cell death (p&amp;lt;0.05). To determine the effect of RB loss on therapeutic response to CDK4/6i, CRISPR mediated RB-knockout (KO) clones were developed in 143B human and K7M2 murine OS cell lines. RB KO cells exhibited sensitivity to CDK4/6i irrespective of RB status. However, levels of CDK4/6i required for 50% growth inhibition in RB KO were 1-3-fold higher using palbociclib, with negligible differences observed with abemaciclib in RB KO vs WT clones. To determine if therapeutic response is achievable in-vivo, a single-agent dosing study was conducted using palbociclib (40mg/kg, SID) and AZD5153 (1mg/kg, BID) in patient-derived xenograft (PDX) model derived from a metastatic lesion in the pelvis (TT2 PDX) harboring a CDK4/6 hyperactivation signature and monoallelic RB loss. Tumor growth reduction and survival was significantly higher in monotherapy groups compared to vehicle. However, one week after dosing was stopped, survival rates based on tumor volume endpoint were 40% and 100% for palbociclib and AZD5153 respectively. In-vivo efficacy of dual CDK46i+BETi is underway. This data provides rationale for further study of novel therapeutic options which may expand the clinical utility of CDK4/6i regardless of RB status. Citation Format: Rada Malko, Pankita H. Pandya, Harlan E. Shannon, Barbara J. Bailey, Erika A. Dobrota, Courtney Young, Farinaz Barghi, Nikan Riyahi, Ryli Justice, Melissa A. Trowbridge, Kathryn L. Coy, Anthony L. Sinn, Khadijeh Bijangi-Vishehsaraei, Micheal J. Ferguson, M. Reza Saadatzadeh, Karen E. Pollok. Targeting CDK4/6 and BET proteins for the treatment of RB+ and RB- osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5719.

Ultrasound Duplex Scanning of Vessels in the Diagnosis of Limb Length Discrepancy in Pediatric Patients with Congenital Vascular Malformations

Ultrasound Duplex Scanning of Vessels in the Diagnosis of Limb Length Discrepancy in Pediatric Patients with Congenital Vascular Malformations

Characterization of Distinctive Teaching Practices in Longitudinal Integrated Clerkships: Perspectives From Students and Faculty

Phenomenon : Longitudinal integrated clerkships (LICs) are novel curricula that place medical students in long-term learning and coaching relationships with faculty and require adaptation of teaching practices on the behalf of faculty to maximize learning outcomes. An understanding of how teaching in an LIC model differs from teaching trainees in more traditional models is critical to ensuring curricular innovation success through faculty development. Approach : A qualitative approach was used to describe the teaching practices of faculty and learning experiences of student participants in longitudinal integrated clerkships in different clinical and community settings. Forty-five faculty and 20 students participated in focus groups. Thematic analysis of focus group data was used to identify differences and similarities between groups, sites, and specialties. Findings : Two groupings of themes emerged in thematic analysis: (1) precepting strategies distinctive to the longitudinal integrated clerkship model and (2) precepting strategies enhanced when employed in the LIC model. Distinct to the LIC model, preceptors and students described the importance of understanding the curricular structure and supporting students in longitudinal care of patients. Enhanced in the LIC model are the strategies of relationship-based teaching, support of autonomy, feedback, and support of longitudinal growth in skills. Insights : Students and faculty across LIC sites were broadly aligned in their opinions of best practices for teaching in an LIC model. The longitudinal relationship between student and faculty in an LIC distinguishes this model from traditional block rotations and a distinctive approach to successful teaching is demonstrated. Preceptors use time afforded to build trusting relationships with students, which created opportunity for novel teaching approaches and enhanced otherwise effective teaching strategies. A focus on orientation to the curricular model and support of longitudinal relationships with patients may serve as an anchor for faculty development efforts in the development of an LIC.

Where you begin is not necessarily where you end: the mental and physical health trajectories of cancer caregivers over time.

Cancer caregiving, a critical component in the cancer-care model, has deleterious effects on the caregiver's physical and mental health. The degree to which these negative effects are uniformly experienced by caregivers is unclear; effects may be exacerbated at the end of life when caregiving is intensified. Not all caregivers have the support of an additional involved support person (secondary caregiver). The impact of the secondary caregiver's absence on the primary caregiver's well-being is understudied. Terminal cancer patient-caregiver dyads (n = 223) were recruited from oncology clinics and followed for six months or until patient death. Longitudinal latent growth models were used to characterize the heterogeneity of caregiver physical health and depressive symptoms; characteristics associated with these trajectories are examined. Caregivers were majority female (74%), white (55%) and patient spouses (60%). Two physical health (moderate, stable; initially good, declining) and two depressive symptom (moderate, stable; high, increasing) trajectories were identified. Declining physical health was more likely among caregivers who were healthiest at baseline, had higher levels of education, lower subjective burden, fewer depressive symptoms, cared for patients with fewer functional limitations and reported fewer caregiving tasks rendered by a secondary caregiver. Those with increasing depressive symptoms were more likely to be white, patient's wife, have higher subjective caregiver burden, lower physical health, and care for a patient with greater functional limitations. Decreasing physical health was evident among caregivers who were initially healthier and reported less assistance from secondary caregivers. Increasing depression was seen in white, female spouses with higher subjective burden. Sample heterogeneity revealed hidden groups unexpectedly at risk in the primary cancer caregiver role to which the oncology care team should be alert.

Gender identity, inter-team competition and leader self-efficacy developmental trajectories in a multi-institutional leader development program

PurposeThis study analyzed three years of data from the Collegiate Leadership Competition to investigate potential differences in longitudinal leader self-efficacy growth between students who identify as men and those who identify as women.Design/methodology/approachSurvey design.FindingsResults indicate that women participants enter their competition experience at higher levels of leader self-efficacy than men and that both groups were able to sustain moderate levels of growth measured several months after the end of the competition.Originality/valueThe gap between men and women in their leader self-efficacy did not change over the several months of measurement. Implications for leadership educators are discussed.

Experiment and Numerical Simulation on Thermal Cycling Performance of YSZ-Based Sealing Coatings with “Brick-Mud” Layered Structure

The failure of premature thermal cycling spalling off is the bottleneck problem currently faced by yttrium oxide partially stabilized zirconia (YSZ) ceramic-based sealing coatings. Studies on the thermal cycling performance of coatings with “brick-mud” structures were carried out by experimental and simulation methods in this paper. The results showed that, as the thickness of “mud” layer increased, the bonding strength of the “brick-mud” structure coatings gradually decreased. When the thickness of the “mud” layer was about 3 μm and 10 μm, the thermal cycling lives of the T1 and T2 coatings were improved by 90.0% and 135.7%, respectively, compared with conventional coating (T0 coating), while that of the T3 coating (containing thick “mud” layers of about 20 μm) was decreased by 81.4%. The stress field of M2 “mud” layers with different thicknesses was subjected to a comprehensive effect by thermal mismatch stress and pores in “brick” layer. Compared with the medium and thick “mud” layers, the thin “mud” layer sustained obvious larger σ22 max and σ12 max, indicating its potential for the preferential initiation of transverse microcracks. In addition, the thin “mud” layer withstood the largest σ11 max and had the strongest potential for longitudinal crack growth. Both transverse and longitudinal cracking could consume energy during thermal cycling and reduce the stress concentration at the top coating/bond coating interface. These were the main reasons for the improvements in the thermal cycling performances of the T1 and T2 coatings. The degree of crack deflection and the capacity of energy dissipation in the “mud” layer increased significantly with its thickness. However, the propagation length of transverse cracks also gradually increased in the meantime. Especially when the “mud” layer was 20 μm, the length of the transverse cracks increased rapidly. Thus, early interlayer delamination failure occurred in the T3 coating during thermal cycling.

Including microbiome information in a multi-trait genomic evaluation: a case study on longitudinal growth performance in beef cattle

BackgroundGrowth rate is an important component of feed conversion efficiency in cattle and varies across the different stages of the finishing period. The metabolic effect of the rumen microbiome is essential for cattle growth, and investigating the genomic and microbial factors that underlie this temporal variation can help maximize feed conversion efficiency at each growth stage.ResultsBy analysing longitudinal body weights during the finishing period and genomic and metagenomic data from 359 beef cattle, our study demonstrates that the influence of the host genome on the functional rumen microbiome contributes to the temporal variation in average daily gain (ADG) in different months (ADG1, ADG2, ADG3, ADG4). Five hundred and thirty-three additive log-ratio transformed microbial genes (alr-MG) had non-zero genomic correlations (rg) with at least one ADG-trait (ranging from |0.21| to |0.42|). Only a few alr-MG correlated with more than one ADG-trait, which suggests that a differential host-microbiome determinism underlies ADG at different stages. These alr-MG were involved in ribosomal biosynthesis, energy processes, sulphur and aminoacid metabolism and transport, or lipopolysaccharide signalling, among others. We selected two alternative subsets of 32 alr-MG that had a non-uniform or a uniform rg sign with all the ADG-traits, regardless of the rg magnitude, and used them to develop a microbiome-driven breeding strategy based on alr-MG only, or combined with ADG-traits, which was aimed at shaping the rumen microbiome towards increased ADG at all finishing stages. Combining alr-MG information with ADG records increased prediction accuracy of genomic estimated breeding values (GEBV) by 11 to 22% relative to the direct breeding strategy (using ADG-traits only), whereas using microbiome information, only, achieved lower accuracies (from 7 to 41%). Predicted selection responses varied consistently with accuracies. Restricting alr-MG based on their rg sign (uniform subset) did not yield a gain in the predicted response compared to the non-uniform subset, which is explained by the absence of alr-MG showing non-zero rg at least with more than one of the ADG-traits.ConclusionsOur work sheds light on the role of the microbial metabolism in the growth trajectory of beef cattle at the genomic level and provides insights into the potential benefits of using microbiome information in future genomic breeding programs to accurately estimate GEBV and increase ADG at each finishing stage in beef cattle.

Look at Grandma! Joint visual attention over video chat during the COVID-19 pandemic

Social interactions are crucial for many aspects of development. One developmentally important milestone is joint visual attention (JVA), or shared attention between child and adult on an object, person, or event. Adults support infants’ development of JVA by structuring the input they receive, with the goal of infants learning to use JVA to communicate. When family members are separated from the infants in their lives, video chat sessions between children and distant relatives allow for shared back-and-forth turn taking interaction across the screen, but JVA is complicated by screen mediation. During video chat, when a participant is looking or pointing at the screen to something in the other person’s environment, there is no line of sight that can be followed to their object of focus. Sensitive caregivers in the remote and local environment with the infant may be able to structure interactions to support infants in using JVA to communicate across screens. We observed naturalistic video chat interactions longitudinally from 50 triads (infant, co-viewing parent, remote grandmother). Longitudinal growth models showed that JVA rate changes with child age (4 to 20 months). Furthermore, grandmother sensitivity predicted JVA rate and infant attention. More complex sessions (sessions involving more people, those with a greater proportion of across-screen JVA, and those where infants initiated more of the JVA) resulted in lower amounts of JVA-per-minute, and evidence of family-level individual differences emerged in all models. We discuss the potential of video chat to enhance communication for separated families in the digital world.