Fasting increases serum bilirubin levels in clinically normal, healthy males but not females : a retrospective study from phase I clinical trial participants

Aim: To examine if fasting affects serum bilirubin levels in clinical healthy males and females. Methods: We utilised retrospective data from phase 1 clinical trials where blood was collected in either a fed or fasting state at screening and pre-dosing time points and analysed for total bilirubin levels as per standard clinical procedures. Participants were clinically healthy males (n = 105) or females (n = 30) aged 18 to 48 inclusive who participated in a phase 1 clinical trial in 2012 or 2013. Results: We found a statistically significant increase in total serum bilirubin levels in fasting males as compared to non-fasting males. The fasting time correlated positively with increased bilirubin levels. The age of the healthy males did not correlate with their fasting bilirubin level. We found no correlation between fasting and bilirubin levels in clinically normal females. Conclusions: The recruitment and screening of volunteers for a clinical trial is a time-consuming and expensive process. This study clearly demonstrates that testing for serum bilirubin should be conducted on non-fasting male subjects. If fasting is required, then participants should not be excluded from a trial based on an elevated serum bilirubin that is deemed non-clinically significant.

The Nagle Royal Commission 25 years on : gaining perspective on two and a half decades of NSW prison reform

This article attempts an audit of changes in the NSW penal system over the last nearly 30 years. Taking the 1978 Nagle Royal Commission findings and analysis as the starting point a comparison is made between the Nagle era and the contemporary scene across a range of practices including imprisonment rates, violence, drug use, deaths in custody, prison conditions, prisoners rights, legal regulation, and others. It is suggested that developments since Nagle are mixed and cannot be attributed to a single logic or force. Major changes include a doubling of imprisonment rates, significant increases in Indigenous and women's imprisonment rates, the apparent ending of institutionalised bashings and the centrality of drug use to imprisonment and to the culture, health and security practices which characterise the current prison experience. The article may constitute a useful starting point for broader attempts to relate current penal practices to far wider changes in the conditions of life under late modernity.

Visualization of predictive distributions for discrete spatial-temporal log Cox processes approximated with MCMC

An important aspect of decision support systems involves applying sophisticated and flexible statistical models to real datasets and communicating these results to decision makers in interpretable ways. An important class of problem is the modelling of incidence such as fire, disease etc. Models of incidence known as point processes or Cox processes are particularly challenging as they are ‘doubly stochastic’ i.e. obtaining the probability mass function of incidents requires two integrals to be evaluated. Existing approaches to the problem either use simple models that obtain predictions using plug-in point estimates and do not distinguish between Cox processes and density estimation but do use sophisticated 3D visualization for interpretation. Alternatively other work employs sophisticated non-parametric Bayesian Cox process models, but do not use visualization to render interpretable complex spatial temporal forecasts. The contribution here is to fill this gap by inferring predictive distributions of Gaussian-log Cox processes and rendering them using state of the art 3D visualization techniques. This requires performing inference on an approximation of the model on a discretized grid of large scale and adapting an existing spatial-diurnal kernel to the log Gaussian Cox process context.

Ozone-induced dissociation of conjugated lipids reveals significant reaction rate enhancements and characteristic odd-electron product ions

Ozone-induced dissociation (OzID) is an alternative ion activation method that relies on the gas phase ion-molecule reaction between a mass-selected target ion and ozone in an ion trap mass spectrometer. Herein, we evaluated the performance of OzID for both the structural elucidation and selective detection of conjugated carbon-carbon double bond motifs within lipids. The relative reactivity trends for \[M + X](+) ions (where X = Li, Na, K) formed via electrospray ionization (ESI) of conjugated versus nonconjugated fatty acid methyl esters (FAMEs) were examined using two different OzID-enabled linear ion-trap mass spectrometers. Compared with nonconjugated analogues, FAMEs derived from conjugated linoleic acids were found to react up to 200 times faster and to yield characteristic radical cations. The significantly enhanced reactivity of conjugated isomers means that OzID product ions can be observed without invoking a reaction delay in the experimental sequence (i.e., trapping of ions in the presence of ozone is not required). This possibility has been exploited to undertake neutral-loss scans on a triple quadrupole mass spectrometer targeting characteristic OzID transitions. Such analyses reveal the presence of conjugated double bonds in lipids extracted from selected foodstuffs. Finally, by benchmarking of the absolute ozone concentration inside the ion trap, second order rate constants for the gas phase reactions between unsaturated organic ions and ozone were obtained. These results demonstrate a significant influence of the adducting metal on reaction rate constants in the fashion Li > Na > K.

Shrinking the keys of discrete-log-type lossy trapdoor functions

To this day, realizations in the standard-model of (lossy) trapdoor functions from discrete-log-type assumptions require large public key sizes, e.g., about Θ(λ 2) group elements for a reduction from the decisional Diffie-Hellman assumption (where λ is a security parameter). We propose two realizations of lossy trapdoor functions that achieve public key size of only Θ(λ) group elements in bilinear groups, with a reduction from the decisional Bilinear Diffie-Hellman assumption. Our first construction achieves this result at the expense of a long common reference string of Θ(λ 2) elements, albeit reusable in multiple LTDF instantiations. Our second scheme also achieves public keys of size Θ(λ), entirely in the standard model and in particular without any reference string, at the cost of a slightly more involved construction. The main technical novelty, developed for the second scheme, is a compact encoding technique for generating compressed representations of certain sequences of group elements for the public parameters.

Normal human mammary epithelial cells spontaneously escape senescence and acquire genomic changes

Senescence and genomic integrity are thought to be important barriers in the development of malignant lesions. Human fibroblasts undergo a limited number of cell divisions before entering an irreversible arrest, called senescence. Here we show that human mammary epithelial cells (HMECs) do not conform to this paradigm of senescence. In contrast to fibroblasts, HMECs exhibit an initial growth phase that is followed by a transient growth plateau (termed selection or M0; refs 3-5), from which proliferative cells emerge to undergo further population doublings (approximately 20-70), before entering a second growth plateau (previously termed senescence or M1; refs 4-6). We find that the first growth plateau exhibits characteristics of senescence but is not an insurmountable barrier to further growth. HMECs emerge from senescence, exhibit eroding telomeric sequences and ultimately enter telomere-based crisis to generate the types of chromosomal abnormalities seen in the earliest lesions of breast cancer. Growth past senescent barriers may be a pivotal event in the earliest steps of carcinogenesis, providing many genetic changes that predicate oncogenic evolution. The differences between epithelial cells and fibroblasts provide new insights into the mechanistic basis of neoplastic transformation.

Parental perceptions of the learner driver log book system in two Australian states

Objective While many jurisdictions internationally now require learner drivers to complete a specified number of hours of supervised driving practice before being able to drive unaccompanied, very few require learner drivers to complete a log book to record this practice and then present it to the licensing authority. Learner drivers in most Australian jurisdictions must complete a log book that records their practice thereby confirming to the licensing authority that they have met the mandated hours of practice requirement. These log books facilitate the management and enforcement of minimum supervised hours of driving requirements. Method Parents of learner drivers in two Australian states, Queensland and New South Wales, completed an online survey assessing a range of factors, including their perceptions of the accuracy of their child’s learner log book and the effectiveness of the log book system. Results The study indicates that the large majority of parents believe that their child’s learner log book is accurate. However, they generally report that the log book system is only moderately effective as a system to measure the number of hours of supervised practice a learner driver has completed. Conclusions The results of this study suggest the presence of a paradox with many parents possibly believing that others are not as diligent in the use of log books as they are or that the system is too open to misuse. Given that many parents report that their child’s log book is accurate, this study has important implications for the development and ongoing monitoring of hours of practice requirements in graduated driver licensing systems.

Reflections on tomorrow’s menu : evidence for inpatient meal preferences at a large tertiary public hospital

There are limited studies that describe patient meal preferences in hospital; however this data is critical to develop menus that address satisfaction and nutrition whilst balancing resources. This quality study aimed to determine preferences for meals and snacks to inform a comprehensive menu revision in a large (929 bed) tertiary public hospital. The method was based on Vivanti et al. (2008) with data collected by two final year dietetic students. The first survey comprised 72 questions, achieved a response rate of 68% (n = 192), with the second more focused at 47 questions achieving a higher response rate of 93% (n = 212). Findings showed over half the patients reporting poor or less than normal appetite, 20% describing taste issues, over a third with a LOS >7 days, a third with a MST _ 2 and less than half eating only from the general menu. Soup then toast was most frequently reported as eaten at home when unwell, and whilst most reported not missing any foods when in hospital (25%), steak was most commonly missed. Hot breakfasts were desired by the majority (63%), with over half preferring toast (even if cold). In relation to snacks, nearly half (48%) wanted something more substantial than tea/coffee/biscuits, with sandwiches (54%) and soup (33%) being suggested. Sandwiches at the evening meal were not popular (6%). Difficulties with using cutlery and meal size selection were identified as issues. Findings from this study had high utility and supported a collaborative and evidenced based approach to a successful major menu change for the hospital.

Collagen-induced activation of the Mr. 72,000 type IV collagenase in normal and malignant human fibroblastoid cells

Although the Mr. 72,000 type IV collagenase (matrix metalloproteinase 2) has been implicated in a variety of normal and pathogenic processes, its activation mechanism in vivo is unclear. We have found that fibroblasts from normal and neoplastic human breast, as well as the sarcomatous human Hs578T and HT1080 cell lines, activate endogenous matrix metalloprotease 2 when cultured on type I collagen gels, but not on plastic, fibronectin, collagen IV, gelatin, matrigel, or basement membrane-like HR9 cell matrix. This activation is monitored by the zymographic detection of Mr 59,000 and/or Mr 62,000 species, requires 2-3 days of culture on vitrogen to manifest, is cycloheximide inhibitable, and correlates with an arborized morphology. A similar activation pattern was seen in these cells in response to Concanavalin A but not transforming growth factor β or 12-O-tetradecanoylphorbol-13-acetate. The interstitial matrix may thus play an important role in regulating matrix degradation in vivo.

Epithelial-mesenchymal interconversions in normal ovarian surface epithelium and ovarian carcinomas : an exception to the norm

Cancer that arises from the ovarian surface epithelium (OSE) accounts for approximately 90% of human ovarian cancer, and is the fourth leading cause of cancer-related deaths among women in developed countries. The pathophysiology of epithelial ovarian cancer is still unclear because of the poor understanding of the complex nature of its development and the unusual mechanism(s) of disease progression. Recent studies have reported epithelial-mesenchymal transition (EMT) in cultured OSE and ovarian cancer cell lines in response to various stimuli, but our understanding of the importance of these observations for normal ovarian physiology and cancer progression is not well established. This review highlights the current literature on EMT-associated events in normal OSE and ovarian cancer cell lines, and discusses its implication for normal ovarian function as well as acquisition of neoplastic phenotypes. The pathological changes in OSE in response to EMT during neoplastic transformation and the contribution of hormones, growth factors, and cytokines that initiate and drive EMT to sustain normal ovarian function, as well as cancer development and progression are also discussed. Finally, emphasis is placed on the clinical implications of EMT and potential therapeutic opportunities that may arise from these observations have been proposed.

Half-wave cycloconverter-based photovoltaic microinverter topology with phase-shift power modulation

A grid-connected microinverter with a reduced number of power conversion stages and fewer passive components is proposed. A high-frequency transformer and a series-resonant tank are used to interface the full-bridge inverter to the half-wave cycloconverter. All power switches are switched with zero-voltage switching. Phase-shift power modulation is used to control the output power of the inverter. A steady-state analysis of the proposed topology is presented to determine the average output power of the inverter. Analysis of soft switching of the full-bridge and the half-wave cycloconverter is presented with respect to voltage gain, quality factor, and phase shift of the inverter. Simulation and experimental results are presented to validate the operation of the proposed topology.

Objectively measured physical activity behavior in children attending a half day preschool program

Obesity rates are increasing in children of all ages, and reduced physical activity (PA) is a likely contributor to this trend. Little is known about the physical activity behavior of preschool-age children, or about the influence of preschool attendance on physical activity. Purpose The purpose of this study was to quantify the physical activity levels of children attending a center-based half-day preschool program. Methods Forty-two 3-to-5-year old children (Mean age = 4.0 ± 0.7, 54.8% Male, Mean BMI = 16.5 ± 5.5, Mean BMI %tile = 52.1 ± 33.5) from four class groups (two morning and two afternoon), wore an Actigraph 7164 accelerometer for the entire halfday program (including classroom learning experiences, snack and recess time) 2 times per week, for 10 weeks (20 activity monitoring records in total). Activity counts for each 5-sec interval were uploaded to a customized data reduction program to determine total counts, minutes of moderate PA (MPA) (3–5.9 METs), and minutes of vigorous PA (VPA) (> = 6 METs) per session. Counts were categorized as either MPA or VPA using the cutpoints developed by Sirard and colleagues (2001). Results Across the four 2.5 hour programs, the average MPA, VPA and total counts (× 103) were 12.4 ± 3.1 minutes, 18.3 ± 4.6 minutes, and 171.1 ± 29.7 counts, respectively. Thus, on average, children accumulated just over 12 minutes of moderateto-vigorous PA per hour of program attendance. The PA variables did not differ significantly by gender, weight status, or time of day. There were, however, significant age differences, with 3-year-olds exhibiting significantly less PA than their 4- and 5-year-old counterparts. Conclusions These results suggest that young children are relatively lowactive while attending preschool. Accordingly, interventions to increase movement opportunities during the preschool day are warranted.

International hermelin brain tumor symposium on matricellular proteins in normal and cancer cell-matrix interactions

The second of the Hermelin Brain Tumor Center Symposia was held once again at Henry Ford Hospital in Detroit, Michigan on October 24th and 25th, 2003. A public conference was held on the 24th while a closed-door session took place on the 25th. The purpose of these symposia is to bring together experts in a particular field of study with the aim to share information with each other and the public, but then to meet privately to present novel data, hold discussions, and share concepts. While the interaction is intended to benefit all involved, the incentive is the expectation that the shared information will aid researchers at the Hermelin Brain Tumor Center in their quest to identify potential therapeutic targets and explore translational therapeutic strategies for the treatment of patients suffering nervous system tumors...

Combining expert opinions in prior elicitation

We consider the problem of combining opinions from different experts in an explicitly model-based way to construct a valid subjective prior in a Bayesian statistical approach. We propose a generic approach by considering a hierarchical model accounting for various sources of variation as well as accounting for potential dependence between experts. We apply this approach to two problems. The first problem deals with a food risk assessment problem involving modelling dose-response for Listeria monocytogenes contamination of mice. Two hierarchical levels of variation are considered (between and within experts) with a complex mathematical situation due to the use of an indirect probit regression. The second concerns the time taken by PhD students to submit their thesis in a particular school. It illustrates a complex situation where three hierarchical levels of variation are modelled but with a simpler underlying probability distribution (log-Normal).

Critical dependence of blood-borne biomarker concentrations on the half-lives of their carrier proteins

Until recently, the low-abundance (LA) range of the serum proteome was an unexplored reservoir of diagnostic information. Today it is increasingly appreciated that a diagnostic goldmine of LA biomarkers resides in the blood stream in complexed association with more abundant higher molecular weight carrier proteins such as albumin and immunoglobulins. As we now look to the possibility of harvesting these LA biomarkers more efficiently through engineered nano-scale particles, mathematical approaches are needed in order to reveal the mechanisms by which blood carrier proteins act as molecular 'mops' for LA diagnostic cargo, and the functional relationships between bound LA biomarker concentrations and other variables of interest such as biomarker intravasation and clearance rates and protein half-lives in the bloodstream. Here we show, by simple mathematical modeling, how the relative abundance of large carrier proteins and their longer half-lives in the bloodstream work together to amplify the total blood concentration of these tiny biomarkers. The analysis further suggests that alterations in the production of biomarkers lead to gradual rather than immediate changes in biomarker levels in the blood circulation. The model analysis also points to the characteristics of artificial nano-particles that would render them more efficient harvesters of tumor biomarkers in the circulation, opening up possibilities for the early detection of curable disease, rather than simply better detection of advanced disease.