A mixed effects model to estimate timing and intensity of pubertal growth from height and secondary sexual characteristics

Abstract Aim: To estimate and compare pubertal growth timing and intensity in height, Tanner stage markers and testis volume. Subjects and methods: Data on height, genital stage, breast stage and pubic hair stage, testis volume and menarche in 103 boys and 74 girls from the Edinburgh Longitudinal Growth Study were analysed. The SITAR model for height and a novel mixed effects logistic model for Tanner stage and testis volume provided estimates of peak velocity (PV, intensity) and age at peak velocity (APV, timing), both overall (from fixed effects) and for individuals (random effects). Results: Based on the six markers, mean APV was 13.0-14.0 years in boys and 12.0-13.1 years in girls, with between-subject standard deviations of ∼1 year. PV for height was 8-9 cm/year by sex and for testis volume 6 ml/year, while Tanner stage increased by 1.2-1.8 stages per year at its peak. The correlations across markers for APV were 0.6-0.8 for boys and 0.8-0.92 for girls, very significantly higher for girls (p = 0.005). Correlations for PV were lower, -0.2-0.6. Conclusions: The mixed effects models perform well in estimating timing and intensity in individuals across several puberty markers. Age at peak velocity correlates highly across markers, but peak velocity less so

Tensile Fracture of Welded Polymer Interfaces: Miscibility, Entanglements and Crazing

Large-scale molecular simulations are performed to investigate tensile failure of polymer interfaces as a function of welding time $t$. Changes in the tensile stress, mode of failure and interfacial fracture energy $G_I$ are correlated to changes in the interfacial entanglements as determined from Primitive Path Analysis. Bulk polymers fail through craze formation, followed by craze breakdown through chain scission. At small $t$ welded interfaces are not strong enough to support craze formation and fail at small strains through chain pullout at the interface. Once chains have formed an average of about one entanglement across the interface, a stable craze is formed throughout the sample. The failure stress of the craze rises with welding time and the mode of craze breakdown changes from chain pullout to chain scission as the interface approaches bulk strength. The interfacial fracture energy $G_I$ is calculated by coupling the simulation results to a continuum fracture mechanics model. As in experiment, $G_I$ increases as $t^{1/2}$ before saturating at the average bulk fracture energy $G_b$. As in previous simulations of shear strength, saturation coincides with the recovery of the bulk entanglement density. Before saturation, $G_I$ is proportional to the areal density of interfacial entanglements. Immiscibiltiy limits interdiffusion and thus suppresses entanglements at the interface. Even small degrees of immisciblity reduce interfacial entanglements enough that failure occurs by chain pullout and $G_I \ll G_b$

Sex differences in predictors and regional patterns of brain age gap estimates

The brain-age-gap estimate (brainAGE) quantifies the difference between chronological age and age predicted by applying machine-learning models to neuroimaging data and is considered a biomarker of brain health. Understanding sex differences in brainAGE is a significant step toward precision medicine. Global and local brainAGE (G-brainAGE and L-brainAGE, respectively) were computed by applying machine learning algorithms to brain structural magnetic resonance imaging data from 1113 healthy young adults (54.45% females; age range: 22–37 years) participating in the Human Connectome Project. Sex differences were determined in G-brainAGE and L-brainAGE. Random forest regression was used to determine sex-specific associations between G-brainAGE and non-imaging measures pertaining to sociodemographic characteristics and mental, physical, and cognitive functions. L-brainAGE showed sex-specific differences; in females, compared to males, L-brainAGE was higher in the cerebellum and brainstem and lower in the prefrontal cortex and insula. Although sex differences in G-brainAGE were minimal, associations between G-brainAGE and non-imaging measures differed between sexes with the exception of poor sleep quality, which was common to both. While univariate relationships were small, the most important predictor of higher G-brainAGE was self-identification as non-white in males and systolic blood pressure in females. The results demonstrate the value of applying sex-specific analyses and machine learning methods to advance our understanding of sex-related differences in factors that influence the rate of brain aging and provide a foundation for targeted interventions

Developing tools to promote culturally competent compassion, courage, and intercultural communication in healthcare

Background: Compassion is an important concept in healthcare, and in addition, care should be delivered in a culturally competent manner, taking into account the values, culture, and health beliefs of the individual. However, the training of nurses and other healthcare professionals may not adequately equip them to practice in a manner which is both compassionate and culturally competent. In this paper, we report on the development of three learning tools, designed to promote the skills and strengthen the capacity of nurses and healthcare professionals to provide culturally competent and compassionate care. Methods: The project involved the participation of six European countries in the development of three learning tools, covering culturally competent compassion, culturally competent courage, and intercultural communication. The principles which informed the methodology derive from the previous work on the Papadopoulos, Tilki and Taylor (PTT) model of transcultural nursing and cultural competence, and were also informed by the Intercultural Education of Nurses in Europe (IENE1 & IENE2) projects. Each partner country was required to produce one tool for each topic area, based on guidance provided by the project co-ordinator, leading to the development of eighteen tools in total. The tools were administered mainly to student nurses to test their feasibility. Results: The emerging tools contained important theoretical and practical components, whereby innovative learning methods and case studies were included. Student nurses enjoyed using the tools, and enjoyed their flexibility. The learning tools enabled students to become stimulated and to engage together leading to a positive learning experience. Discussion: The tools allow for a positive learning experience and reflection of good practice to take place. The flexibility and content of the tools allows for them to be of equal value to other healthcare professionals as well as nursing staff. Conclusion: The tools were initially utilised mainly with student nurses and were received with a positive response. Work is now in place to further implement the tools and evaluate the longer term effects among a range of healthcare professionals and service user health outcomes

Leucine Regulates Zoosporic Germination and Infection by Phytophthora erythroseptica

Pink rot (Phytophthora erythroseptica) of potato is a major concern in many potato production regions. The pathogen produces zoospores that serve as a primary inoculum for infection. To understand how the pink rot incidence is related to pathogen population, qualitative, and quantitative chemical analyses were conducted. It was demonstrated that P. erythroseptica zoospores required a minimal population of 103 zoospores/ml (threshold) for initiating germination and the subsequent infection; the percentage of zoosporic germination was positively correlated with the density of zoospores above the threshold. To elucidate the density-dependent behavior, zoospore exudate (ZE) was extracted from high-density (105/ml) zoospore suspension. Zoosporic inocula of P. erythroseptica at different concentrations were inoculated on potato tubers. Necrotic lesions were caused by inoculum with 100 zoospores per inoculation site; 5 zoospores per site did not cause lesions on the tuber. However, five zoospores did cause lesions when they were placed in ZE, suggesting ZE contained chemical compounds that regulate germination of zoospores. ZE was collected and analyzed using liquid chromatography mass spectroscopy (LC-MS). Results showed that the amino acid leucine was associated with zoosporic germination. Therefore, zoosporic germination and infection of P. erythroseptica were mediated by signaling molecules secreted from zoospores

Walks4work: Rationale and study design to investigate walking at lunchtime in the workplace setting

Background: Following recruitment of a private sector company, an 8week lunchtime walking intervention was implemented to examine the effect of the intervention on modifiable cardiovascular disease risk factors, and further to see if walking environment had any further effect on the cardiovascular disease risk factors. Methods. For phase 1 of the study participants were divided into three groups, two lunchtime walking intervention groups to walk around either an urban or natural environment twice a week during their lunch break over an 8week period. The third group was a waiting-list control who would be invited to join the walking groups after phase 1. In phase 2 all participants were encouraged to walk during their lunch break on self-selecting routes. Health checks were completed at baseline, end of phase 1 and end of phase 2 in order to measure the impact of the intervention on cardiovascular disease risk. The primary outcome variables of heart rate and heart rate variability were measured to assess autonomic function associated with cardiovascular disease. Secondary outcome variables (Body mass index, blood pressure, fitness, autonomic response to a stressor) related to cardiovascular disease were also measured. The efficacy of the intervention in increasing physical activity was objectively monitored throughout the 8-weeks using an accelerometer device. Discussion. The results of this study will help in developing interventions with low researcher input with high participant output that may be implemented in the workplace. If effective, this study will highlight the contribution that natural environments can make in the reduction of modifiable cardiovascular disease risk factors within the workplace. © 2012 Brown et al.; licensee BioMed Central Ltd

In Situ Proteolysis to Generate Crystals for Structure Determination: An Update

For every 100 purified proteins that enter crystallization trials, an average of 30 form crystals, and among these only 13–15 crystallize in a form that enables structure determination. In 2007, Dong et al reported that the addition of trace amounts of protease to crystallization trials—in situ proteolysis—significantly increased the number of proteins in a given set that produce diffraction quality crystals. 69 proteins that had previously resisted structure determination were subjected to crystallization with in situ proteolysis and ten crystallized in a form that led to structure determination (14.5% success rate). Here we apply in situ proteolysis to over 270 new soluble proteins that had failed in the past to produce crystals suitable for structure determination. These proteins had produced no crystals, crystals that diffracted poorly, or produced twinned and/or unmanageable diffraction data. The new set includes yeast and prokaryotic proteins, enzymes essential to protozoan parasites, and human proteins such as GTPases, chromatin remodeling proteins, and tyrosine kinases. 34 proteins yielded deposited crystal structures of 2.8 Å resolution or better, for an overall 12.6% success rate, and at least ten more yielded well-diffracting crystals presently in refinement. The success rate among proteins that had previously crystallized was double that of those that had never before yielded crystals. The overall success rate is similar to that observed in the smaller study, and appears to be higher than any other method reported to rescue stalled protein crystallography projects

Glycogen Synthase Kinase (GSK) 3β phosphorylates and protects nuclear myosin 1c from proteasome-mediated degradation to activate rDNA transcription in early G1 cells

Nuclear myosin 1c (NM1) mediates RNA polymerase I (pol I) transcription activation and cell cycle progression by facilitating PCAF-mediated H3K9 acetylation, but the molecular mechanism by which NM1 is regulated remains unclear. Here, we report that at early G1 the glycogen synthase kinase (GSK) 3β phosphorylates and stabilizes NM1, allowing for NM1 association with the chromatin. Genomic analysis by ChIP-Seq showed that this mechanism occurs on the rDNA as active GSK3β selectively occupies the gene. ChIP assays and transmission electron microscopy in GSK3β-/- mouse embryonic fibroblasts indicated that at G1 rRNA synthesis is suppressed due to decreased H3K9 acetylation leading to a chromatin state incompatible with transcription. We found that GSK3β directly phosphorylates the endogenous NM1 on a single serine residue (Ser-1020) located within the NM1 C-terminus. In G1 this phosphorylation event stabilizes NM1 and prevents NM1 polyubiquitination by the E3 ligase UBR5 and proteasome-mediated degradation. We conclude that GSK3β-mediated phosphorylation of NM1 is required for pol I transcription activation

'An interesting paper but not sufficiently theoretical’ : what does theorising in social research look like

This article explores the concept of theorising in social research: what is theorising; how does theorising look to those doing it and how can it be explained as a practice. The article draws on different sources, including accounts of theory and theorising in the literature as well as first-hand reporting by academics. A view is reached of theorising as a personal undertaking involving a commitment to comprehend the world. It is argued that theorising is driven by the identification of interesting problems (practical or theoretical or both) and a motivation to solve them. Theorising involves a shift of awareness from subsidiary to focal and such a shift allows a more abstract level of understanding. Theorising tends to be an individual undertaking which draws on personal knowledge, but it is only made possible by psychological tools which have been handed down from the past, ones which need to be accessed, understood and adapted. Theorising requires a disciplined creativity in which the imagination is channelled into finding solutions that are compatible with observed data