Standardising corneal nerve fibre length for nerve tortuosity increases its association with measures of diabetic neuropathy

AIMS: Recent studies on corneal markers have advocated corneal nerve fibre length as the most important measure of diabetic peripheral neuropathy. The aim of this study was to determine if standardizing corneal nerve fibre length for tortuosity increases its association with other measures of diabetic peripheral neuropathy. METHODS: Two hundred and thirty-one individuals with diabetes with either predominantly mild or absent neuropathic changes and 61 control subjects underwent evaluation of diabetic neuropathy symptom score, neuropathy disability score, testing with 10-g monofilament, quantitative sensory testing (warm, cold, vibration detection) and nerve conduction studies. Corneal nerve fibre length and corneal nerve fibre tortuosity were measured using corneal confocal microscopy. A tortuosity-standardised corneal nerve fibre length variable was generated by dividing corneal nerve fibre length by corneal nerve fibre tortuosity. Differences in corneal nerve morphology between individuals with and without diabetic peripheral neuropathy and control subjects were determined and associations were estimated between corneal morphology and established tests of, and risk factors for, diabetic peripheral neuropathy. RESULTS: The tortuosity-standardised corneal nerve fibre length variable was better than corneal nerve fibre length in demonstrating differences between individuals with diabetes, with and without neuropathy (tortuosity-standardised corneal nerve fibre length variable: 70.5 ± 27.3 vs. 84.9 ± 28.7, P < 0.001, receiver operating characteristic area under the curve = 0.67; corneal nerve fibre length: 15.9 ± 6.9 vs. 18.4 ± 6.2 mm/mm(2) , P = 0.004, receiver operating characteristic area under the curve = 0.64). Furthermore, the tortuosity-standardised corneal nerve fibre length variable demonstrated a significant difference between the control subjects and individuals with diabetes, without neuropathy, while corneal nerve fibre length did not (tortuosity-standardised corneal nerve fibre length variable: 94.3 ± 27.1 vs. 84.9 ± 28.7, P = 0.028; corneal nerve fibre length: 20.1 ± 6.3 vs. 18.4 ± 6.2 mm/mm(2) , P = 0.084). Correlations between corneal nerve fibre length and established measures of neuropathy and risk factors for neuropathy were higher when a correction was made for the nerve tortuosity. CONCLUSIONS: Standardizing corneal nerve fibre length for tortuosity enhances the ability to differentiate individuals with diabetes, with and without neuropathy.

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.

Socio-demographic characteristics, modifiable lifestyle factors, and health as predictors of mental health in midlife and older Australian women: a multilevel investigation

Background Poor mental health is a significant cause of morbidity and mortality, yet debate continues about factors most likely to predict poor mental health outcomes. Objective This cohort study examines the influence of modifiable lifestyle factors, menopausal symptoms, and physical health on the mental health of midlife and older Australian women. Methods: Random sampling was used to recruit women aged 40-55, from rural and urban areas of Queensland, Australia. Overall, 340 women completed mailed surveys on socio-demographic characteristics, midlife symptoms (Greene Climacteric Scale©), modifiable lifestyle factors, and mental health (SF-12©) in 2001, 2004 and 2011. Hierarchical repeated-measure models were used to explore the correlates of poor mental health over time. Results The mean age [SD] at baseline was 55 [2.7] years, most were married (73%, n=248) and 18% were pre-menopausal. The model suggested that variance in mental health widened and showed a non-linear increase with age. Decrements in mental health were associated with an increase in midlife symptoms (Greene psychological scale, P <0.01; Greene somatic scale, P <0.05), time (P <0.01), poor physical health (P <0.01) and individual variance (P <0.01). Socio-demographics and lifestyle factors had little influence on mental health over time. Conclusion Findings suggest that while women’s mental health may decline during midlife, the effect is temporary; in older women, physical health and individual factors seem to be increasingly significant. This research highlights the importance of active health promotion as a means of enhancing both physical and mental health in midlife women.

Security analysis of Australian and E.U. e-passport implementation

This paper makes a formal security analysis of the current Australian e-passport implementation using model checking tools CASPER/CSP/FDR. We highlight security issues in the current implementation and identify new threats when an e-passport system is integrated with an automated processing system like SmartGate. The paper also provides a security analysis of the European Union (EU) proposal for Extended Access Control (EAC) that is intended to provide improved security in protecting biometric information of the e-passport bearer. The current e-passport specification fails to provide a list of adequate security goals that could be used for security evaluation. We fill this gap; we present a collection of security goals for evaluation of e-passport protocols. Our analysis confirms existing security weaknesses that were previously identified and shows that both the Australian e-passport implementation and the EU proposal fail to address many security and privacy aspects that are paramount in implementing a secure border control mechanism. ACM Classification C.2.2 (Communication/Networking and Information Technology – Network Protocols – Model Checking), D.2.4 (Software Engineering – Software/Program Verification – Formal Methods), D.4.6 (Operating Systems – Security and Privacy Protection – Authentication)

Factor Five : Transforming the Global Economy through 80% Improvements in Resource Productivity

The 21st century will see monumental change. Either the human race will use its knowledge and skills and change the way it interacts with the environment, or the environment will change the way it interacts with its inhabitants. In the first case, the focus of this book, we would see our sophisticated understanding in areas such as physics, chemistry, engineering, biology, planning, commerce, business and governance accumulated over the last 1,000 years brought to bear on the challenge of dramatically reducing our pressure on the environment. The second case however is the opposite scenario, involving the decline of the planet’s ecosystems until they reach thresholds where recovery is not possible, and following which we have no idea what happens. For instance, if we fail to respond to Sir Nicolas Stern’s call to meet appropriate stabilisation trajectories for greenhouse gas emissions, and we allow the average temperature of our planets surface to increase by 4-6 degrees Celsius, we will see staggering changes to our environment, including rapidly rising sea level, withering crops, diminishing water reserves, drought, cyclones, floods… allowing this to happen will be the failure of our species, and those that survive will have a deadly legacy. In this update to the 1997 International Best Seller, Factor Four, Ernst von Weizsäcker again leads a team to present a compelling case for sector wide advances that can deliver significant resource productivity improvements over the coming century. The purpose of this book is to inspire hope and to then inform meaningful action in the coming decades to respond to the greatest challenge our species has ever faced – that of living in harmony with our planet and its other inhabitants.

Detection and quantification of tear phospholipids and cholesterol in contact lens deposits : the effect of contact lens material and lens care solution

PURPOSE. To examine the deposition of tear phospholipids and cholesterol onto worn contact lenses and the effect of lens material and lens care solution. METHODS. Lipids were extracted from tears and worn contact lenses using 2:1 chloroform: Methanol and the extract washed with aqueous ammonium acetate, before analysis by electrospray ionization tandem mass spectrometry (ESI-MS/MS). RESULTS. Twenty-three molecular lipids from the sphingomyelin (SM) and phosphatidylcholine (PC) classes were detected in tears, with total concentrations of each class determined to be 5 ± 1 pmol/μL (~3.8 μg/mL) and 6 ± 1 pmol/μL (~ 4.6μg/mL), respectively. The profile of individual phospholipids in both of these classes was shown to be similar in contact lens deposits. Deposition of representative polar and nonpolar lipids were shown to be significantly higher on senofilcon A contact lenses, with ~59 ng/lens SM, 195 ng/lens PC, and 9.9 μg/lens cholesterol detected, whereas balafilcon A lens extracts contained ~19 ng/lens SM, 19 ng/lens PC, and 3.9 μg/lens cholesterol. Extracts from lenses disinfected and cleaned with two lens care solutions showed no significant differences in total PC and SM concentrations; however, a greater proportion of PC than SM was observed, compared with that in tears. CONCLUSIONS. Phospholipid deposits extracted from worn contact lenses show a molecular profile similar to that in tears. The concentration of representative polar and nonpolar lipids deposited onto contact lenses is significantly affected by lens composition. There is a differential efficacy in the removal of PC and SM with lens care solutions.

Direct detection of additives and degradation products from polymers by liquid extraction surface analysis employing chip-based nanospray mass spectrometry

RATIONALE: Polymer-based surface coatings in outdoor applications experience accelerated degradation due to exposure to solar radiation, oxygen and atmospheric pollutants. These deleterious agents cause undesirable changes to the aesthetic and mechanical properties of the polymer, reducing its lifetime. The use of antioxidants such as hindered amine light stabilisers (HALS) retards these degradative processes; however, mechanisms for HALS action and polymer degradation are poorly understood. METHODS: Detection of the HALS TINUVINW123 (bis(1-octyloxy-2,2,6,6-tetramethyl-4-piperidyl) sebacate) and the polymer degradation products directly from a polyester-based coil coating was achieved by liquid extraction surface analysis (LESA) coupled to a triple quadrupole QTRAPW 5500 mass spectrometer. The detection of TINUVINW123 and melamine was confirmed by the characteristic fragmentation pattern observed in LESA-MS/MS spectra that was identical to that reported for authentic samples. RESULTS: Analysis of an unstabilised coil coating by LESA-MS after exposure to 4 years of outdoor field testing revealed the presence of melamine (1,3,5-triazine-2,4,6-triamine) as a polymer degradation product at elevated levels. Changes to the physical appearance of the coil coating, including powder-like deposits on the coating's surface, were observed to coincide with melamine deposits and are indicative of the phenomenon known as polymer ' blooming'. CONCLUSIONS: For the first time, in situ detection of analytes from a thermoset polymer coating was accomplished without any sample preparation, providing advantages over traditional extraction-analysis approaches and some contemporary ambient MS methods. Detection of HALS and polymer degradation products such as melamine provides insight into the mechanisms by which degradation occurs and suggests LESA-MS is a powerful new tool for polymer analysis. Copyright (C) 2012 John Wiley & Sons, Ltd.

Design Minds The Big Picture Toolkit

The Design Minds The Big Picture Toolkit was one of six K7-12 secondary school design toolkits commissioned by the State Library of Queensland (SLQ) Asia Pacific Design Library (APDL), to facilitate the delivery of the Stage 1 launch of its Design Minds online platform (www.designminds.org.au) partnership initiative with Queensland Government Arts Queensland and the Smithsonian Cooper-Hewitt National Design Museum, on June 29, 2012. Design Minds toolkits are practical guides, underpinned by a combination of one to three of the Design Minds model phases of ‘Inquire’, ‘Ideate’ and ‘Implement’ (supported by at each stage with structured reflection), to enhance existing school curriculum and empower students with real life design exercises, within the classroom environment. Toolkits directly identify links to Naplan, National Curriculum, C2C and Professional Standards benchmarks, as well as the student capabilities of successful and creative 21st century citizens they seek to engender through design thinking. Inspired by the Unlimited: Designing for the Asia Pacific Generation Workshop 2010 (http://eprints.qut.edu.au/47762/), this toolkit explores, through three distinct exercises, ‘design for the other 90%’, addressing tools and approaches to diverse and changing social, cultural, technological and environmental challenges. The Design Minds The Big Picture Toolkit challenges students to be active agents for change and to think creatively and optimistically about solutions to future global issues that deliver social, economic and environmental benefits. More generally, it aims to facilitate awareness in young people, of the role of design in society and the value of design thinking skills in generating strategies to solve basic to complex systemic challenges, as well as to inspire post-secondary pathways and idea generation for education. The toolkit encourages students and teachers to develop sketching, making, communication, presentation and collaboration skills to improve their design process, as well as explore further inquiry (background research) to enhance the ideation exercises. Exercise 1 focuses on the ‘Inquire’ phase, Exercise 2 the ‘Inquire’ and ‘Ideate’ phases, and Exercise 3 concentrates on the ‘Implement’ phase. Depending on the intensity of the focus, the unit of work could be developed over a 4-5 week program (approximately 4-6 x 60 minute lessons/workshops) or as smaller workshops treated as discrete learning experiences. The toolkit is available for public download from http://designminds.org.au/the-big-picture/ on the Design Minds website.

Survival of rat functional dental pulp cells in vascularized tissue engineering chambers

Regenerative endodontics aims to preserve, repair or regenerate the dental pulp tissue. Dental pulp stem cells, have a potential use in dental tissue generation. However, specific requirements to drive the dental tissue generation are still obscured. We established an in vivo model for studying the survival of dental pulp cells (DPC) and their potential to generate dental pulp tissue. DPC were mixed with collagen scaffold with or without slow release bone morphogenic protein 4 (BMP-4) and fibroblast growth factor 2 (FGF2). The cell suspension was transplanted into a vascularized tissue engineering chamber in the rat groin. Tissue constructs were harvested after 2, 4, 6, and 8 weeks and processed for histomorphological and immunohistochemical analysis. After 2 weeks newly formed tissue with new blood vessel formation were observed inside the chamber. DPC were found around dentin, particularly around the vascular pedicle and also close to the gelatin microspheres. Cell survival, was confirmed up to 8 weeks after transplantation. Dentin Sialophosphoprotein (DSPP) positive matrix production was detected in the chamber, indicating functionality of dental pulp progenitor cells. This study demonstrates the potential of our tissue engineering model to study rat dental pulp cells and their behavior in dental pulp regeneration, for future development of an alternative treatment using these techniques.

Indexes of insulin resistance and secretion in obese children and adolescents : a validation study

OBJECTIVE To assess the concurrent validity of fasting indexes of insulin sensitivity and secretion in - obese prepubertal (Tanner stage 1) children and pubertal (Tanner stages 2-5) glucose tolerance test (FSIVGTT) as a criterion measure. RESEARCH DESIGN AND METHODS Eighteen obese children and adolescents (11 girls and 7 boys, mean age 12.2 +/- 2.4 years, mean BMI 35.4 +/- 6.2 kg/m(2), mean BMI-SDS 3.5 +/- 0.5, 7 prepubertal and I I pubertal) participated in the study. All participants underwent an insulin-modified FSIVGTT on two occasions, and 15 repeated this test a third time (mean 12.9 and 12.0 weeks apart). S-i measured by the FSIVGTT was compared with homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), fasting glucose-to-insulin ratio (FGIR), and fasting insulin (estimates of insulin sensitivity derived from fasting samples). The acute insulin response (AIR) measured by the FSIVGTT was compared with HOMA of percent beta-cell function (HOMA-beta%), FGIR, and fasting insulin (estimates of insulin secretion derived from fasting samples). RESULTS There was a significant negative correlation between HOMA-IR and S-i (r = -0.89, r = -0.90, and r = -0.81, P < 0.01) and a significant positive correlation between QUICKI and S-i (r = 0.89, r = 0.90, and r = 0.81, P < 0.01) at each time point. There was a significant positive correlation between FGIR and S-i (r = 0.91, r = 0.91, and r = 0.82, P < 0.01) and a significant negative correlation between fasting insulin and S-i (r = -90, r = -0.90, and r = -0.88, P < 0.01). HOMA-beta% was not as strongly correlated with AIR (r = 0.60, r = 0.54, and r = 0.61, P < 0.05). CONCLUSIONS HOMA-IR, QUICKI, FGIR, and fasting insulin correlate strongly with S-i assessed by the FSIVGTT in obese children and adolescents. Correlations between HOMA-β% FGIR and fasting insulin, and AIR were not as strong. Indexes derived from fasting samples are a valid tool for assessing insulin sensitivity in prepubertal and pubertal obese children.

Associations between individual and workplace risk factors for self-reported neck pain and disability among female office workers

A cross-sectional survey of female office workers (n=333) was undertaken to determine the level of neck pain and disability (Neck Disability Index—NDI) and to explore the relationship between individual and workplace risk factors with the NDI score and the presence of pain. Workers reported nil (32%), mild (53%), moderate (14%) and severe (1%) neck pain. There were more risk factors associated with the NDI score than the presence of neck pain. The presence of neck pain was associated with a history of neck trauma (OR: 4.8), using a graduated lens (OR: 4.6), and negative affectivity (OR: 2.7) in the multiple regression model. Factors associated with higher NDI score were using the computer mouse for more than 6 h per day, higher negative affectivity, older age and an uncomfortable workstation. These results suggest that measuring the level of neck pain and disability rather than just the presence of neck pain provides more specific directives for the prevention and management of this disorder.

Intervening to reduce workplace sitting time : how and when do changes to sitting time occur?

Objective To investigate how and when changes in workplace sitting time occurred following a workplace intervention to inform evaluation of intervention success. Method The 4-week Stand Up Comcare study (June–September 2011) aimed to reduce workplace sitting time via regularly interrupting and replacing sitting time throughout the day. Activity monitor (activPAL3) workplace data from control (n=22) and intervention participants (n=21) were analysed. Differences in the number and usual duration of sitting bouts were used to evaluate how change occurred. To examine when change occurred, intervention effects were compared by hour since starting work and hour of the workday. Change in workplace activity (sitting, standing, stepping) was examined to further inform alignment with intervention messages. Individual variability was examined in how and when the change occurred. Results Overall, behavioural changes aligned with intervention aims. All intervention participants reduced total workplace sitting time, though there was wide individual variability observed (range −29 to −262 min per 8 h workday). On average, intervention participants reduced number of sitting bouts (−4.6 bouts (95% CI −10.1 to 1.0), p=0.106) and usual sitting bout duration (−5.6 min (95% CI −9.8 to −1.4, p=0.011)) relative to controls. Sitting time reductions were observed across the workday, though intervention effects varied by hour of the day (p=0.015). The intervention group successfully adopted the Stand Up and Sit Less intervention messages across the day. Conclusion These analyses confirmed that this workplace intervention successfully modified sitting behaviour as intended (ie, fewer and shorter sitting bouts, with changes occurring throughout the day).

Physical activity patterns of inner-city elementary schoolchildren

Purpose This study aimed to objectively measure the physical activity (PA) characteristics of a racially and ethnically diverse sample of inner-city elementary schoolchildren and to examine the influence of sex, race/ethnicity, grade level, and weight status on PA. Methods A total of 470 students in grades 4-6 from six inner-city schools in Philadelphia wore an ActiGraph GT3X+ accelerometer (Actigraph, Pensacola, FL) for up to 7 d. The resultant data were uploaded to a customized Visual Basic EXCEL macro to determine the time spent in sedentary (SED), light-intensity PA (LPA), and moderate- to vigorous-intensity PA (MVPA). Results On average, students accumulated 48 min of MVPA daily. Expressed as a percentage of monitoring time, students were sedentary for 63% of the time, in LPA 31% of the time, and in MVPA 6% of the time. Across all race/ethnicity and grade level groups, boys exhibited significantly higher levels of MVPA than girls did; fifth-grade boys exhibited significantly lower MVPA levels than fourth-and sixth-grade boys did, and sixth-grade girls exhibited significantly lower MVPA levels than fourth-and fifth-grade girls did. Hispanic children exhibited lower levels of MVPA than children from other racial/ethnic groups did, and overweight and obese children exhibited significantly lower MVPA levels than children in the healthy weight range did. Across the entire sample, only 24.3% met the current public health guidelines for PA. Physical inactivity was significantly greater among females, Hispanics, and overweight and obese students. Conclusions Fewer than one in four inner-city schoolchildren accumulated the recommended 60 min of MVPA daily. These findings highlight the need for effective and sustainable programs to promote PA in inner-city youth.

Using objective physical activity measures with youth : How many days of monitoring are needed?

Purpose The purpose of this study was to establish the minimal number of days of monitoring required for accelerometers to assess usual physical activity in children. Methods A total of 381 students (189 M, 192 F) wore a CSA 7164 uniaxial accelerometer for seven consecutive days. To examine age-related trends students were grouped as follows: Group I: grades 1-3 (N = 92); Group II: grades 4-6 (N = 98); Group III: grades 7-9 (N = 97); Group IV: grades 10-12 (N = 94). Average daily time spent in moderate-to-vigorous physical activity (MVPA) was calculated from minute-by-minute activity counts using the regression equation developed by Freedson et al. (1997). Results Compared with adolescents in grades 7 to 12, children in grades 1 to 6 exhibited less day-to-day variability in MVPA behavior. Spearman-Brown analysts indicated that between 4 and 5 d of monitoring would be necessary to a achieve a reliability of 0.80 in children, and between 8 and 9 d of monitoring would be necessary to achieve a reliability of 0.80 in adolescents. Within all grade levels, the 7-d monitoring protocol produced acceptable estimates of daily participation in MVPA (R = 0.76 (0.71-0.81) to 0.87 (0.84-0.90)). Compared with weekdays, children exhibited significantly higher levels of MVPA on weekends, whereas adolescents exhibited significantly lower levels of MVPA on weekends. Principal components analysis revealed two distinct time components for MVPA during the day for children (early morning, rest of the day), and three distinct time components for MVPA during the day for adolescents (morning, afternoon, early evening). Conclusions These results indicate that a 7-d monitoring protocol provides reliable estimates of usual physical activity behavior in children and adolescents and accounts for potentially important differences in weekend versus weekday activity behavior as well as differences in activity patterns within a given day.

An MMP13-selective inhibitor delays primary tumor growth and the onset of tumor-associated osteolytic lesions in experimental models of breast cancer

We investigated the effects of the matrix metalloproteinase 13 (MMP13)-selective inhibitor, 5-(4-{4-[4-(4-fluorophenyl)-1,3-oxazol-2-yl]phenoxy}phenoxy)-5-(2-methoxyethyl) pyrimidine-2,4,6(1H,3H,5H)-trione (Cmpd-1), on the primary tumor growth and breast cancer-associated bone remodeling using xenograft and syngeneic mouse models. We used human breast cancer MDA-MB-231 cells inoculated into the mammary fat pad and left ventricle of BALB/c Nu/Nu mice, respectively, and spontaneously metastasizing 4T1.2-Luc mouse mammary cells inoculated into mammary fat pad of BALB/c mice. In a prevention setting, treatment with Cmpd-1 markedly delayed the growth of primary tumors in both models, and reduced the onset and severity of osteolytic lesions in the MDA-MB-231 intracardiac model. Intervention treatment with Cmpd-1 on established MDA-MB-231 primary tumors also significantly inhibited subsequent growth. In contrast, no effects of Cmpd-1 were observed on soft organ metastatic burden following intracardiac or mammary fat pad inoculations of MDA-MB-231 and 4T1.2-Luc cells respectively. MMP13 immunostaining of clinical primary breast tumors and experimental mice tumors revealed intra-tumoral and stromal expression in most tumors, and vasculature expression in all. MMP13 was also detected in osteoblasts in clinical samples of breast-to-bone metastases. The data suggest that MMP13-selective inhibitors, which lack musculoskeletal side effects, may have therapeutic potential both in primary breast cancer and cancer-induced bone osteolysis.