Advanced glycation endproducts in horses with insulin-induced laminitis

Advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of cancer, inflammatory conditions and diabetic complications. An interaction of AGEs with their receptor (RAGE) results in increased release of pro-inflammatory cytokines and reactive oxygen species (ROS), causing damage to susceptible tissues. Laminitis, a debilitating foot condition of horses, occurs in association with endocrine dysfunction and the potential involvement of AGE and RAGE in the pathogenesis of the disease has not been previously investigated. Glucose transport in lamellar tissue is thought to be largely insulin-independent (GLUT-1), which may make the lamellae susceptible to protein glycosylation and oxidative stress during periods of increased glucose metabolism. Archived lamellar tissue from horses with insulin-induced laminitis (n=4), normal control horses (n=4) and horses in the developmental stages (6 h, 12 h and 24 h) of the disease (n=12) was assessed for AGE accumulation and the presence of oxidative protein damage and cellular lipid peroxidation. The equine-specific RAGE gene was identified in lamellar tissue, sequenced and is now available on GenBank. Lamellar glucose transporter (GLUT-1 and GLUT-4) gene expression was assessed quantitatively with qRT-PCR in laminitic and control horses and horses in the mid-developmental time-point (24 h) of the disease. Significant AGE accumulation had occurred by the onset of insulin-induced laminitis (48 h) but not at earlier time-points, or in control horses. Evidence of oxidative stress was not found in any group. The equine-specific RAGE gene was not expressed differently in treated and control animals, nor was the insulin-dependent glucose transporter GLUT-4. However, the glucose transporter GLUT-1 was increased in lamellar tissue in the developmental stages of insulin-induced laminitis compared to control horses and the insulin-independent nature of the lamellae may facilitate AGE formation. However, due to the lack of AGE accumulation during disease development and a failure to detect an increase in ROS or upregulation of RAGE, it appears unlikely that oxidative stress and protein glycosylation play a central role in the pathogenesis of acute, insulin-induced laminitis.

Prevalence of hallux valgus in the general population : a systematic review and meta-analysis

BACKGROUND: Hallux valgus (HV) is a foot deformity commonly seen in medical practice, often accompanied by significant functional disability and foot pain. Despite frequent mention in a diverse body of literature, a precise estimate of the prevalence of HV is difficult to ascertain. The purpose of this systematic review was to investigate prevalence of HV in the overall population and evaluate the influence of age and gender. METHODS: Electronic databases (Medline, Embase, and CINAHL) and reference lists of included papers were searched to June 2009 for papers on HV prevalence without language restriction. MeSH terms and keywords were used relating to HV or bunions, prevalence and various synonyms. Included studies were surveys reporting original data for prevalence of HV or bunions in healthy populations of any age group. Surveys reporting prevalence data grouped with other foot deformities and in specific disease groups (e.g. rheumatoid arthritis, diabetes) were excluded. Two independent investigators quality rated all included papers on the Epidemiological Appraisal Instrument. Data on raw prevalence, population studied and methodology were extracted. Prevalence proportions and the standard error were calculated, and meta-analysis was performed using a random effects model. RESULTS: A total of 78 papers reporting results of 76 surveys (total 496,957 participants) were included and grouped by study population for meta-analysis. Pooled prevalence estimates for HV were 23% in adults aged 18-65 years (CI: 16.3 to 29.6) and 35.7% in elderly people aged over 65 years (CI: 29.5 to 42.0). Prevalence increased with age and was higher in females [30% (CI: 22 to 38)] compared to males [13% (CI: 9 to 17)]. Potential sources of bias were sampling method, study quality and method of HV diagnosis. CONCLUSIONS: Notwithstanding the wide variation in estimates, it is evident that HV is prevalent; more so in females and with increasing age. Methodological quality issues need to be addressed in interpreting reports in the literature and in future research.

Alternating direction implicit numerical method for the space and time fractional Bloch-Torrey equation in 3-D

Recently, some authors have considered a new diffusion model–space and time fractional Bloch-Torrey equation (ST-FBTE). Magin et al. (2008) have derived analytical solutions with fractional order dynamics in space (i.e., _ = 1, β an arbitrary real number, 1 < β ≤ 2) and time (i.e., 0 < α < 1, and β = 2), respectively. Yu et al. (2011) have derived an analytical solution and an effective implicit numerical method for solving ST-FBTEs, and also discussed the stability and convergence of the implicit numerical method. However, due to the computational overheads necessary to perform the simulations for nuclear magnetic resonance (NMR) in three dimensions, they present a study based on a two-dimensional example to confirm their theoretical analysis. Alternating direction implicit (ADI) schemes have been proposed for the numerical simulations of classic differential equations. The ADI schemes will reduce a multidimensional problem to a series of independent one-dimensional problems and are thus computationally efficient. In this paper, we consider the numerical solution of a ST-FBTE on a finite domain. The time and space derivatives in the ST-FBTE are replaced by the Caputo and the sequential Riesz fractional derivatives, respectively. A fractional alternating direction implicit scheme (FADIS) for the ST-FBTE in 3-D is proposed. Stability and convergence properties of the FADIS are discussed. Finally, some numerical results for ST-FBTE are given.

An implicit RBF meshless method for a fractal mobile/immobile transport model

Fractional differential equation is used to describe a fractal model of mobile/immobile transport with a power law memory function. This equation is the limiting equation that governs continuous time random walks with heavy tailed random waiting times. In this paper, we firstly propose a finite difference method to discretize the time variable and obtain a semi-discrete scheme. Then we discuss its stability and convergence. Secondly we consider a meshless method based on radial basis functions (RBF) to discretize the space variable. By contrast to conventional FDM and FEM, the meshless method is demonstrated to have distinct advantages: calculations can be performed independent of a mesh, it is more accurate and it can be used to solve complex problems. Finally the convergence order is verified from a numerical example is presented to describe the fractal model of mobile/immobile transport process with different problem domains. The numerical results indicate that the present meshless approach is very effective for modeling and simulating of fractional differential equations, and it has good potential in development of a robust simulation tool for problems in engineering and science that are governed by various types of fractional differential equations.

Digital Storytelling within a Service-Learning Partnership: Technology as Product and Process for University Students and Culturally and Linguistically Diverse High School Youth

This chapter describes a university/high school partnership focused on digital storytelling. It also explains the multi-stage process used to establish this successful partnership and project. The authors discuss the central role that technology played in developing this university/high school partnership, a collaboration that extended the impact of a digital storytelling project to reach high school students, university students, educators, high school administrators, and the local community. Valuing a reflective process that can lead to the creation of a powerful final product, the authors describe the impact of digital storytelling on multiple stakeholders, including the 13 university students and 33 culturally and linguistically diverse high school youth who participated during the fall of 2009. In addition, the chapter includes reflections from university and high school student participants expressed during focus groups conducted throughout the project. While most participants had a positive experience with the project, complications with the technology component often caused frustrations and additional challenges. Goals for sharing this project are to critically evaluate digital storytelling, describe lessons learned, and recommend good practices for others working within a similar context or with parallel goals.

Numerical analysis of the time variable fractional order mobile-immobile advection-dispersion model

Many physical processes exhibit fractional order behavior that varies with time or space. The continuum of order in the fractional calculus allows the order of the fractional operator to be considered as a variable. In this paper, we consider the time variable fractional order mobile-immobile advection-dispersion model. Numerical methods and analyses of stability and convergence for the fractional partial differential equations are quite limited and difficult to derive. This motivates us to develop efficient numerical methods as well as stability and convergence of the implicit numerical methods for the fractional order mobile immobile advection-dispersion model. In the paper, we use the Coimbra variable time fractional derivative which is more efficient from the numerical standpoint and is preferable for modeling dynamical systems. An implicit Euler approximation for the equation is proposed and then the stability of the approximation are investigated. As for the convergence of the numerical scheme we only consider a special case, i.e. the time fractional derivative is independent of time variable t. The case where the time fractional derivative depends both the time variable t and the space variable x will be considered in the future work. Finally, numerical examples are provided to show that the implicit Euler approximation is computationally efficient.

Practical client puzzles in the standard model

Client puzzles are cryptographic problems that are neither easy nor hard to solve. Most puzzles are based on either number theoretic or hash inversions problems. Hash-based puzzles are very efficient but so far have been shown secure only in the random oracle model; number theoretic puzzles, while secure in the standard model, tend to be inefficient. In this paper, we solve the problem of constucting cryptographic puzzles that are secure int he standard model and are very efficient. We present an efficient number theoretic puzzle that satisfies the puzzle security definition of Chen et al. (ASIACRYPT 2009). To prove the security of our puzzle, we introduce a new variant of the interval discrete logarithm assumption which may be of independent interest, and show this new problem to be hard under reasonable assumptions. Our experimental results show that, for 512-bit modulus, the solution verification time of our proposed puzzle can be up to 50x and 89x faster than the Karame-Capkum puzzle and the Rivest et al.'s time-lock puzzle respectively. In particular, the solution verification tiem of our puzzle is only 1.4x slower than that of Chen et al.'s efficient hash based puzzle.

In the pursuit of effective affective computing : the relationship between features and registration

For facial expression recognition systems to be applicable in the real world, they need to be able to detect and track a previously unseen person's face and its facial movements accurately in realistic environments. A highly plausible solution involves performing a "dense" form of alignment, where 60-70 fiducial facial points are tracked with high accuracy. The problem is that, in practice, this type of dense alignment had so far been impossible to achieve in a generic sense, mainly due to poor reliability and robustness. Instead, many expression detection methods have opted for a "coarse" form of face alignment, followed by an application of a biologically inspired appearance descriptor such as the histogram of oriented gradients or Gabor magnitudes. Encouragingly, recent advances to a number of dense alignment algorithms have demonstrated both high reliability and accuracy for unseen subjects [e.g., constrained local models (CLMs)]. This begs the question: Aside from countering against illumination variation, what do these appearance descriptors do that standard pixel representations do not? In this paper, we show that, when close to perfect alignment is obtained, there is no real benefit in employing these different appearance-based representations (under consistent illumination conditions). In fact, when misalignment does occur, we show that these appearance descriptors do work well by encoding robustness to alignment error. For this work, we compared two popular methods for dense alignment-subject-dependent active appearance models versus subject-independent CLMs-on the task of action-unit detection. These comparisons were conducted through a battery of experiments across various publicly available data sets (i.e., CK+, Pain, M3, and GEMEP-FERA). We also report our performance in the recent 2011 Facial Expression Recognition and Analysis Challenge for the subject-independent task.

Disobedient Citizens : Press Depictions of Striking School Teachers in NSW and Anti-Vietnam War Demonstrators in NSW and Victoria in 1968

Across Australia in 1968, students demonstrating against the Vietnam War engaged in confrontational behaviour. The metropolitan daily newspapers,the most important source of news for most people, enthusiastically reported the scenes. The demonstrations were exciting. Sensational headlines and photographs captured the interest of readers and influenced their opinions. But radical opposition to government policies at the time was not limited to university students opposing the Vietnam War. Teachers had become increasingly critical of conditions in schools, with Victorian secondary school teachers having stopped work on a number of occasions since 1965. In October 1968, both primary and secondary school teachers in New South Wales participated in eastern Australia’s first state-wide teachers’ strike. As Sydney’s Sun commented on 1 October 1968, “The teachers’ strike threw the ... education system into chaos ... A huge proportion of the State’s 2764 schools were silent and empty.” Similarities with the anti-war demonstrations were obvious. Although not as confrontational, the New South Wales teachers’ strike was a publicity-seeking action. This examination of the teachers’ more restrained, but more effective, approach to challenging government policies provides a new voice and vision to our understandings of the diverse nature of radicalism in Australia in the 1960s.

Cellular settings mediating Src Substrate switching between Focal Adhesion Kinase Tyrosine 861 and CUB-domain-containing protein 1 (CDCP1) Tyrosine 734

Reciprocal interactions between Src family kinases (SFKs) and focal adhesion kinase (FAK) are critical during changes in cell attachment. Recently it has been recognized that another SFK substrate, CUB-domain-containing protein 1 (CDCP1), is differentially phosphorylated during these events. However, the molecular processes underlying SFK-mediated phosphorylation of CDCP1 are poorly understood. Here we identify a novel mechanism in which FAK tyrosine 861 and CDCP1-Tyr-734 compete as SFK substrates and demonstrate cellular settings in which SFKs switch between these sites. Our results show that stable CDCP1 expression induces robust SFK-mediated phosphorylation of CDCP1-Tyr-734 with concomitant loss of p-FAK-Tyr-861 in adherent HeLa cells. SFK substrate switching in these cells is dependent on the level of expression of CDCP1 and is also dependent on CDCP1-Tyr-734 but is independent of CDCP1-Tyr-743 and -Tyr-762. In HeLa CDCP1 cells, engagement of SFKs with CDCP1 is accompanied by an increase in phosphorylation of Src-Tyr-416 and a change in cell morphology to a fibroblastic appearance dependent on CDCP1-Tyr-734. SFK switching between FAK-Tyr-861 and CDCP1-Tyr-734 also occurs during changes in adhesion of colorectal cancer cell lines endogenously expressing these two proteins. Consistently, increased p-FAK-Tyr-861 levels and a more epithelial morphology are seen in colon cancer SW480 cells silenced for CDCP1. Unlike protein kinase Cδ, FAK does not appear to form a trimeric complex with Src and CDCP1. These data demonstrate novel aspects of the dynamics of SFK-mediated cell signaling that may be relevant during cancer progression.

The influence of smoking status on malnutrition risk and 1-year mortality in outpatients with chronic obstructive pulmonary disease.

Introduction:  Smoking status in outpatients with chronic obstructive pulmonary disease (COPD) has been associated with a low body mass index (BMI) and reduced mid-arm muscle circumference (Cochrane & Afolabi, 2004). Individuals with COPD identified as malnourished have also been found to be twice as likely to die within 1 year compared to non-malnourished patients (Collins et al., 2010). Although malnutrition is both preventable and treatable, it is not clear what influence current smoking status, another modifiable risk factor, has on malnutrition risk. The current study aimed to establish the influence of smoking status on malnutrition risk and 1-year mortality in outpatients with COPD. Methods:  A prospective nutritional screening survey was carried out between July 2008 and May 2009 at a large teaching hospital (Southampton General Hospital) and a smaller community hospital within Hampshire (Lymington New Forest Hospital). In total, 424 outpatients with a diagnosis of COPD were routinely screened using the ‘Malnutrition Universal Screening Tool’, ‘MUST’ (Elia, 2003); 222 males, 202 females; mean (SD) age 73 (9.9) years; mean (SD) BMI 25.9 (6.4) kg m−2. Smoking status on the date of screening was obtained for 401 of the outpatients. Severity of COPD was assessed using the GOLD criteria, and social deprivation determined using the Index of Multiple Deprivation (Nobel et al., 2008). Results:  The overall prevalence of malnutrition (medium + high risk) was 22%, with 32% of current smokers at risk (who accounted for 19% of the total COPD population). In comparison, 19% of nonsmokers and ex-smokers were likely to be malnourished [odds ratio, 1.965; 95% confidence interval (CI), 1.133–3.394; P = 0.015]. Smoking status remained an independent risk factor for malnutrition even after adjustment for age, social deprivation and disease-severity (odds ratio, 2.048; 95% CI, 1.085–3.866; P = 0.027) using binary logistic regression. After adjusting for age, disease severity, social deprivation, smoking status, malnutrition remained a significant predictor of 1-year mortality [odds ratio (medium + high risk versus low risk), 2.161; 95% CI, 1.021–4.573; P = 0.044], whereas smoking status did not (odds ratio for smokers versus ex-smokers + nonsmokers was 1.968; 95% CI, 0.788–4.913; P = 0.147). Discussion:  This study highlights the potential importance of combined nutritional support and smoking cessation in order to treat malnutrition. The close association between smoking status and malnutrition risk in COPD suggests that smoking is an important consideration in the nutritional management of malnourished COPD outpatients. Conclusions:  Smoking status in COPD outpatients is a significant independent risk factor for malnutrition and a weaker (nonsignificant) predictor of 1-year mortality. Malnutrition significantly predicted 1 year mortality. References:  Cochrane, W.J. & Afolabi, O.A. (2004) Investigation into the nutritional status, dietary intake and smoking habits of patients with chronic obstructive pulmonary disease. J. Hum. Nutr. Diet.17, 3–11. Collins, P.F., Stratton, R.J., Kurukulaaratchym R., Warwick, H. Cawood, A.L. & Elia, M. (2010) ‘MUST’ predicts 1-year survival in outpatients with chronic obstructive pulmonary disease. Clin. Nutr.5, 17. Elia, M. (Ed) (2003) The ‘MUST’ Report. BAPEN. http://www.bapen.org.uk (accessed on March 30 2011). Nobel, M., McLennan, D., Wilkinson, K., Whitworth, A. & Barnes, H. (2008) The English Indices of Deprivation 2007. http://www.communities.gov.uk (accessed on March 30 2011).