Estimation of growth parameters from multiple-recapture data

This article develops a method for analysis of growth data with multiple recaptures when the initial ages for all individuals are unknown. The existing approaches either impute the initial ages or model them as random effects. Assumptions about the initial age are not verifiable because all the initial ages are unknown. We present an alternative approach that treats all the lengths including the length at first capture as correlated repeated measures for each individual. Optimal estimating equations are developed using the generalized estimating equations approach that only requires the first two moment assumptions. Explicit expressions for estimation of both mean growth parameters and variance components are given to minimize the computational complexity. Simulation studies indicate that the proposed method works well. Two real data sets are analyzed for illustration, one from whelks (Dicathais aegaota) and the other from southern rock lobster (Jasus edwardsii) in South Australia.

Groucho homologue Grg5 interacts with the transcription factor Runx2-Cbfa1 and modulates its activity during postnatal growth in mice

Runx2-Cbfal, a Runt transcription factor, plays important roles during skeletal development. It is required for differentiation and function of osteoblasts. In its absence, chondrocyte hypertrophy is severely impaired and there is no vascularization of cartilage templates during skeletal development. These tissue-specific functions of Runx2 are likely to be dependent on its interaction with other proteins. We have therefore searched for proteins that may modulate the activity of Runx2. The yeast two-hybrid system was used to identify a groucho homologue, Grg5, as a Runx2-interacting protein. Grg5 enhances Runx2 activity in a cell culture-based assay and by analyses of postnatal growth in mice we demonstrate that Grg5 and Runx2 interact genetically. We also show that Runx2 haploinsufficiency in the absence of Grg5 results in a more severe delay in ossification of cranial sutures and fontanels than occurs with Runx2 haploinsufficiency on a wild-type background. Finally, we find shortening of the proliferative and hypertrophic zones, and expansion of the resting zone in the growth plates of Runx2(+/-)Grg5(-/-) mice that are associated with reduced Ihh expression and Indian hedgehog (Ihh) signaling. We therefore conclude that Grg5 enhances Runx2 activity in vivo.

Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth plates

Gene-targeted disruption of Grg5, a mouse homologue of Drosophila groucho (gro), results in postnatal growth retardation in mice. The growth defect, most striking in approximately half of the Grg5 null mice, occurs during the first 4-5 weeks of age, but most mice recover retarded growth later. We used the nonlinear mixed-effects model to fit the growth data of wild-type, heterozygous, and Grg5 null mice. On the basis of preliminary evidence suggesting an interaction between Grg5 and the transcription factor Cbfa1/Runx2, critical for skeletal development, we further investigated the skeleton in the mice. A long bone growth plate defect was identified, which included shorter zones of proliferative and hypertrophic chondrocytes and decreased trabecular bone formation. This decreased trabecular bone formation is likely caused by a reduced recruitment of osteoblasts into the growth plate region of Grg5 null mice. Like the growth defect, the growth plate and trabecular bone abnormality improved as the mice grew older. The growth plate defect was associated with reduced Indian hedgehog expression and signaling. We suggest that Grg5, a transcriptional coregulator, modulates the activities of transcription factors, such as Cbfa1/Runx2 in vivo to affect Ihh expression and the function of long bone growth plates.

Estimating equations for parameters in stochastic growth models from tag-recapture data

James (1991, Biometrics 47, 1519-1530) constructed unbiased estimating functions for estimating the two parameters in the von Bertalanffy growth curve from tag-recapture data. This paper provides unbiased estimating functions for a class of growth models that incorporate stochastic components and explanatory variables. a simulation study using seasonal growth models indicates that the proposed method works well while the least-squares methods that are commonly used in the literature may produce substantially biased estimates. The proposed model and method are also applied to real data from tagged rack lobsters to assess the possible seasonal effect on growth.

An improved Fabens method for estimation of growth parameters in the vonBertalanffy model with individual asymptotes

In the analysis of tagging data, it has been found that the least-squares method, based on the increment function known as the Fabens method, produces biased estimates because individual variability in growth is not allowed for. This paper modifies the Fabens method to account for individual variability in the length asymptote. Significance tests using t-statistics or log-likelihood ratio statistics may be applied to show the level of individual variability. Simulation results indicate that the modified method reduces the biases in the estimates to negligible proportions. Tagging data from tiger prawns (Penaeus esculentus and Penaeus semisulcatus) and rock lobster (Panulirus ornatus) are analysed as an illustration.

Growth curves with explanatory variables and estimation of the effect of tagging

The von Bertalanffy growth model is extended to incorporate explanatory variables. The generalized model includes the switched growth model and the seasonal growth model as special cases, and can also be used to assess the tagging effect on growth. Distribution-free and consistent estimating functions are constructed for estimation of growth parameters from tag-recapture data in which age at release is unknown. This generalizes the work of James (1991, Biometrics 47 1519-1530) who considered the classical model and allowed for individual variability in growth. A real dataset from barramundi (Lates calcarifer) is analysed to estimate the growth parameters and possible effect of tagging on growth.

Modelling growth rate of Penaeus monodon Fabricius in intensively managed ponds: effects of temperature, pond age and stocking density

Records of shrimp growth and water quality made during 12 crops from each of 48 ponds, over a period of 6.5 years, were provided by a Queensland, Australia, commercial shrimp farm, These data were analysed with a new growth model derived from the Gompertz model. The results indicate that water temperature, mortality and pond age significantly affect growth rates. After 180 days, shrimp reach 34 g at constant 30 degrees C, but only 15 g after the same amount of time at 20 degrees C. Mortality, through thinning the density of shrimp in the ponds, increased the growth rate, but the effect is small. With continual production, growth rates at first remained steady, then appeared to decrease for the sixth and seventh crop, after which they have increased steadily with each crop. It appears that conservative pond management, together with a gradual improvement in husbandry techniques, particularly feed management, brought about this change. This has encouraging implications for the long-term sustainability of the farming methods used. The growth model can be used to predict productivity, and hence, profitability, of new aquaculture locations or new production strategies.

Growth and meaning from negotiating the complex journey of being an Emergency Medical Dispatcher

Emergency Medical Dispatchers (EMDs) are charged with taking the calls of those who ring the national emergency number for urgent medical assistance, for dispatching paramedical crews, and for providing as much assistance as can be offered remotely until paramedics arrive. In a job role which is filled with vicarious trauma, emergency situations, pressure, abuse, grief and loss, EMDs are often challenged in maintaining their mental health. The seemingly senseless death of a teenager who commits suicide, the devastating loss of a baby to Sudden Infant Death Syndrome, lives lost through natural disasters, and multiple vehicle fatalities are only a few of the types of experiences EMDs are faced with in the course of their work. However, amongst the horror are positive stories such as coaching a caller to negotiate the birth of a baby and saving a life in jeopardy from heart failure. EMD’s need to cope with the daily challenges of the role; make sense of their work and create meaning in order to have a fulfilled and sustainable career. Although some people in this work struggle greatly to withstand the impacts of vicarious trauma, there are also stories of personal growth. In this Chapter we use a case study to explore how meaning is made for those who are an auditory witness to a continual flux of trauma for others and how the traumatic experiences EMDs bear witness to can also be a catalyst for posttraumatic growth.

A biomechanical investigation of fusionless growth modulation implants for spinal scoliosis treatment

This thesis studied a new minimally invasive implant for scoliosis correction that aims to correct the deformity without fusing the spine, thereby allowing movement and growth in the spine following surgery. The effect of two different vertebral body implant (staple) designs on the stiffness of the spine, using calf spines as an in vitro model, was studied. The results showed that the implants decreased spinal stiffness, with associated potential damage to the growth plates due to the staple tips. There were no significant differences in stiffness between the two staple designs tested.

Uropathogenic Escherichia Coli engages CD14-dependent signaling to enable bladder-macrophage-dependent control of acute urinary tract infection

Background CD14, a coreceptor for several pattern recognition receptors and a widely used monocyte/macrophage marker, plays a key role in host responses to gram-negative bacteria. Despite the central role of CD14 in the inflammatory response to lipopolysaccharide and other microbial products and in the dissemination of bacteria in some infections, the signaling networks controlled by CD14 during urinary tract infection (UTI) are unknown. Methods We used uropathogenic Escherichia coli (UPEC) infection of wild-type (WT) C57BL/6 and Cd14−/− mice and RNA sequencing to define the CD14-dependent transcriptional signature and the role of CD14 in host defense against UTI in the bladder. Results UPEC induced the upregulation of Cd14 and the monocyte/macrophage-related genes Emr1/F4/80 and Csf1r/c-fms, which was associated with lower UPEC burdens in WT mice, compared with Cd14−/− mice. Exacerbation of infection in Cd14−/− mice was associated with the absence of a 491-gene transcriptional signature in the bladder that encompassed multiple host networks not previously associated with this receptor. CD14-dependent pathways included immune cell trafficking, differential cytokine production in macrophages, and interleukin 17 signaling. Depletion of monocytes/macrophages in the bladder by administration of liposomal clodronate led to higher UPEC burdens. Conclusions This study identifies new host protective and signaling roles for CD14 in the bladder during UPEC UTI.

Insights into the growth of newly formed particles in a subtropical urban environment

The role of different chemical compounds, particularly organics, involved in the new particle formation (NPF) and its consequent growth are not fully understood. Therefore, this study was conducted to investigate the chemical composition of aerosol particles during NPF events in an urban subtropical environment. Aerosol chemical composition was measured along with particle number size distribution (PNSD) and several other air quality parameters at five sites across an urban subtropical environment. An Aerodyne compact Time-of-Flight Aerosol Mass Spectrometer (c-TOF-AMS) and a TSI Scanning Mobility Particle Sizer (SMPS) measured aerosol chemical composition (particles above 50 nm in vacuum aerodynamic diameter) and PNSD (particles within 9-414 nm in mobility diameter), respectively. Five NPF events, with growth rates in the range 3.3-4.6 nm, were detected at two of the sites. The NPF events happened on relatively warmer days with lower condensation sink (CS). Temporal percent fractions of organics increased after the particles grew enough to have a significant contribution to particles volume, while the mass fraction of ammonium and sulphate decreased. This uncovered the important role of organics in the growth of newly formed particles. Three organic markers, factors f43, f44 and f57, were calculated and the f44 vs f43 trends were compared between nucleation and non-nucleation days. K-means cluster analysis was performed on f44 vs f43 data and it was found that they follow different patterns on nucleation days compared to non-nucleation days, whereby f43 decreased for vehicle emission generated particles, while both f44 and f43 decreased for NPF generated particles. It was found for the first time that vehicle generated and newly formed particles cluster in different locations on f44 vs f43 plot and this finding can be potentially used as a tool for source apportionment of measured particles.

Human bladder uroepithelial cells synergize with monocytes to promote IL-10 synthesis and other cytokine responses to Uropathogenic Escherichia coli

Urinary tract infections are a major source of morbidity for women and the elderly, with Uropathogenic Escherichia coli (UPEC) being the most prevalent causative pathogen. Studies in recent years have defined a key anti-inflammatory role for Interleukin-10 (IL-10) in urinary tract infection mediated by UPEC and other uropathogens. We investigated the nature of the IL-10-producing interactions between UPEC and host cells by utilising a novel co-culture model that incorporated lymphocytes, mononuclear and uroepithelial cells in histotypic proportions. This co-culture model demonstrated synergistic IL-10 production effects between monocytes and uroepithelial cells following infection with UPEC. Membrane inserts were used to separate the monocyte and uroepithelial cell types during infection and revealed two synergistic IL-10 production effects based on contact-dependent and soluble interactions. Analysis of a comprehensive set of immunologically relevant biomarkers in monocyte-uroepithelial cell co-cultures highlighted that multiple cytokine, chemokine and signalling factors were also produced in a synergistic or antagonistic fashion. These results demonstrate that IL-10 responses to UPEC occur via multiple interactions between several cells types, implying a complex role for infection-related IL-10 during UTI. Development and application of the co-culture model described in this study is thus useful to define the degree of contact dependency of biomarker production to UPEC, and highlights the relevance of histotypic co-cultures in studying complex host-pathogen interactions.

Genome-wide mapping of cystitis due to Streptococcus agalactiae and Escherichia coli in mice identifies a unique bladder transcriptome that signifies pathogen-specific antimicrobial defense against urinary tract infection

The most common causes of urinary tract infections (UTIs) are Gram-negative pathogens such as Escherichia coli; however, Gram-positive organisms including Streptococcus agalactiae, or group B streptococcus (GBS), also cause UTI. In GBS infection, UTI progresses to cystitis once the bacteria colonize bladder, but the host responses triggered in the bladder immediately following infection are largely unknown. Here, we used genome-wide expression profiling to map the bladder transcriptome of GBS UTI in mice infected transurethrally with uropathogenic GBS that was cultured from a 35 year-old women with cystitis. RNA from bladders was applied to Affymetrix Gene-1.0ST microarrays; qRT-PCR was used to analyze selected gene responses identified in array datasets. A surprisingly small significant gene list of 172 genes was identified at 24h; this compared to 2507 genes identified in a side-by-side comparison with uropathogenic E. coli (UPEC). No genes exhibited significantly altered expression at 2h in GBS-infected mice according to arrays despite high bladder bacterial loads at this early time point. The absence of a marked early host response to GBS juxtaposed with broad-based bladder responses activated by UPEC at 2h. Bioinformatics analyses including integrative systems-level network mapping revealed multiple activated biological pathways in the GBS cystitis transcriptome that regulate leukocyte activation, inflammation, apoptosis, and cytokine-chemokine biosynthesis. These findings define a novel, minimalistic type of bladder host response triggered by GBS UTI, which comprises collective antimicrobial pathways that differ dramatically from those activated by UPEC. Overall, this study emphasizes the unique nature of bladder immune activation mechanisms triggered by distinct uropathogens.

Clinical Escherichia coli isolates utilize alpha-hemolysin to inhibit in vitro epithelial cytokine production

Uropathogenic Escherichia coli is the primary cause of urinary tract infections, which affects over 60% of women during their lifetime. UPEC exhibits a number of virulence traits that facilitate colonization of the bladder, including inhibition of cytokine production by bladder epithelial cells. The goal of this study was to identify the mechanism of this inhibition. We observed that cytokine suppression was associated with rapid cytotoxicity toward epithelial cells. We found that cytotoxicity, cytokine suppression and alpha-hemolysin production were all tightly linked in clinical isolates. We screened a UPEC fosmid library and identified clones that gained the cytotoxicity and cytokine-suppression phenotypes. Both clones contained fosmids encoding a PAI II(J96)-like domain and expressed the alpha-hemolysin (hlyA) encoded therein. Mutation of the fosmid-encoded hly operon abolished cytotoxicity and cytokine suppression. Similarly, mutation of the chromosomal hlyCABD operon of UPEC isolate F11 also abolished these phenotypes, and they could be restored by introducing the PAI II(J96)-like domain-encoding fosmid. We also examined the role of alpha-hemolysin in cytokine production both in the murine UTI model as well as patient specimens. We conclude that E. coli utilizes alpha-hemolysin to inhibit epithelial cytokine production in vitro. Its contribution to inflammation during infection requires further study.