Showing papers by "University of Newcastle published in 2015"

A new criterion for assessing discriminant validity in variance-based structural equation modeling

Abstract: Discriminant validity assessment has become a generally accepted prerequisite for analyzing relationships between latent variables. For variance-based structural equation modeling, such as partial least squares, the Fornell-Larcker criterion and the examination of cross-loadings are the dominant approaches for evaluating discriminant validity. By means of a simulation study, we show that these approaches do not reliably detect the lack of discriminant validity in common research situations. We therefore propose an alternative approach, based on the multitrait-multimethod matrix, to assess discriminant validity: the heterotrait-monotrait ratio of correlations. We demonstrate its superior performance by means of a Monte Carlo simulation study, in which we compare the new approach to the Fornell-Larcker criterion and the assessment of (partial) cross-loadings. Finally, we provide guidelines on how to handle discriminant validity issues in variance-based structural equation modeling.

Advances and Challenges of Liposome Assisted Drug Delivery.

Abstract: The application of liposomes to assist drug delivery has already had a major impact on many biomedical areas. They have been shown to be beneficial for stabilizing therapeutic compounds, overcoming obstacles to cellular and tissue uptake, and improving biodistribution of compounds to target sites in vivo. This enables effective delivery of encapsulated compounds to target sites while minimizing systemic toxicity. Liposomes present as an attractive delivery system due to their flexible physicochemical and biophysical properties, which allow easy manipulation to address different delivery considerations. Despite considerable research in the last 50 years and the plethora of positive results in preclinical studies, the clinical translation of liposome assisted drug delivery platforms has progressed incrementally. In this review, we will discuss the advances in liposome assisted drug delivery, biological challenges that still remain, and current clinical and experimental use of liposomes for biomedical applications. The translational obstacles of liposomal technology will also be presented.

The ONIOM Method and Its Applications

Abstract: Lung Wa Chung,† W. M. C. Sameera,‡ Romain Ramozzi,‡ Alister J. Page, Miho Hatanaka,‡ Galina P. Petrova, Travis V. Harris,‡,⊥ Xin Li, Zhuofeng Ke, Fengyi Liu, Hai-Bei Li, Lina Ding, and Keiji Morokuma*,‡ †Department of Chemistry, South University of Science and Technology of China, Shenzhen 518055, China ‡Fukui Institute for Fundamental Chemistry, Kyoto University, 34-4 Takano Nishihiraki-cho, Sakyo, Kyoto 606-8103, Japan Newcastle Institute for Energy and Resources, The University of Newcastle, Callaghan 2308, Australia Faculty of Chemistry and Pharmacy, University of Sofia, Bulgaria Boulevard James Bourchier 1, 1164 Sofia, Bulgaria Department of Chemistry, State University of New York at Oswego, Oswego, New York 13126, United States State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China Key Laboratory of Macromolecular Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an, Shaanxi 710119, China School of Ocean, Shandong University, Weihai 264209, China School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China

A meta-meta-analysis of the effect of physical activity on depression and anxiety in non-clinical adult populations

Abstract: Amidst strong efforts to promote the therapeutic benefits of physical activity for reducing depression and anxiety in clinical populations, little focus has been directed towards the mental health benefits of activity for non-clinical populations. The objective of this meta-meta-analysis was to systematically aggregate and quantify high-quality meta-analytic findings of the effects of physical activity on depression and anxiety for non-clinical populations. A systematic search identified eight meta-analytic outcomes of randomised trials that investigated the effects of physical activity on depression or anxiety. The subsequent meta-meta-analyses were based on a total of 92 studies with 4310 participants for the effect of physical activity on depression and 306 study effects with 10,755 participants for the effect of physical activity on anxiety. Physical activity reduced depression by a medium effect [standardised mean difference (SMD) = -0.50; 95% CI: -0.93 to -0.06] and anxiety by a small effect (SMD = -0.38; 95% CI: -0.66 to -0.11). Neither effect showed significant heterogeneity across meta-analyses. These findings represent a comprehensive body of high-quality evidence that physical activity reduces depression and anxiety in non-clinical populations.

Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites

Abstract: Asthma is prevalent in Western countries, and recent explanations have evoked the actions of the gut microbiota. Here we show that feeding mice a high-fibre diet yields a distinctive gut microbiota, which increases the levels of the short-chain fatty acid, acetate. High-fibre or acetate-feeding led to marked suppression of allergic airways disease (AAD, a model for human asthma), by enhancing T-regulatory cell numbers and function. Acetate increases acetylation at the Foxp3 promoter, likely through HDAC9 inhibition. Epigenetic effects of fibre/acetate in adult mice led us to examine the influence of maternal intake of fibre/acetate. High-fibre/acetate feeding of pregnant mice imparts on their adult offspring an inability to develop robust AAD. High fibre/acetate suppresses expression of certain genes in the mouse fetal lung linked to both human asthma and mouse AAD. Thus, diet acting on the gut microbiota profoundly influences airway responses, and may represent an approach to prevent asthma, including during pregnancy.

Adjuvant ovarian suppression in premenopausal breast cancer

Abstract: We randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would improve disease-free survival, as compared with tamoxifen alone. In the primary analysis, 46.7% of the patients had not received chemotherapy previously, and 53.3% had received chemotherapy and remained premenopausal. RESULTS After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen–ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P = 0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen–ovarian suppression group and 78.0% in the tamoxifen group (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane–ovarian suppression group (hazard ratio for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87). CONCLUSIONS Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improvement was seen with the use of exemestane plus ovarian suppression. (Funded by Pfizer and others; SOFT ClinicalTrials.gov number, NCT00066690.)

Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants

Abstract: Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

A recently evolved hexose transporter variant confers resistance to multiple pathogens in wheat.

Abstract: As there are numerous pathogen species that cause disease and limit yields of crops, such as wheat (Triticum aestivum), single genes that provide resistance to multiple pathogens are valuable in crop improvement. The mechanistic basis of multi-pathogen resistance is largely unknown. Here we use comparative genomics, mutagenesis and transformation to isolate the wheat Lr67 gene, which confers partial resistance to all three wheat rust pathogen species and powdery mildew. The Lr67 resistance gene encodes a predicted hexose transporter (LR67res) that differs from the susceptible form of the same protein (LR67sus) by two amino acids that are conserved in orthologous hexose transporters. Sugar uptake assays show that LR67sus, and related proteins encoded by homeoalleles, function as high-affinity glucose transporters. LR67res exerts a dominant-negative effect through heterodimerization with these functional transporters to reduce glucose uptake. Alterations in hexose transport in infected leaves may explain its ability to reduce the growth of multiple biotrophic pathogen species.

The Evolution of Cognitive Bias

Abstract: On the surface, cognitive biases appear to be puzzling when viewed through an evolutionary lens. Because they depart from standards of logic and accuracy, they appear to be design flaws instead of examples of good evolutionary engineering. Biases are often ascribed to cognitive “constraints” or flaws in the design of the mind that were somehow not overcome by evolution. To the evolutionary psychologist, however, evolved psychological mechanisms are expected to solve particular problems well, in ways that contributed to fitness ancestrally. Viewed in this way, cognitive biasescould have evolved because they positively impacted fitness. They are, then, not necessarily designflaws—instead, they could be design features. This chapter describes research documenting adaptive biases across many domains. These include inferences about danger, the cooperativeness of others, and the sexual and romantic interests of prospective mates. This chapter also addresses the question of why biases often seem to be implemented at the cognitive level, producing genuine misperceptions, rather than merely biases in enacted behavior. Keywords: evolutionary psychology; cognitive biases; error management theory; social cognition; sexual misperception

The TREAT-NMD DMD Global Database: Analysis of More than 7,000 Duchenne Muscular Dystrophy Mutations

Abstract: Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations).

The impact of dynamic capabilities on operational marketing and technological capabilities: investigating the role of environmental turbulence

Abstract: Marketing and technological capabilities are primary drivers of a firm’s performance and thus of central interest to managers. Yet the way in which these two capabilities align with changing environments to secure superior performance remains unclear. Drawing on the dynamic capability view and data from a survey of 228 firms, this study proposes a model of how frequent dynamic capability utilization, assessed through its underlying processes of sensing and reconfiguring, relates to marketing and technological capabilities, as well as how market, technological, and competitor turbulence might affect these relationships. The results show that frequent sensing and reconfiguring have stronger positive effects in environments characterized by high competitor turbulence; however, frequent sensing can have negative relationships with marketing and technological capabilities in stable environments. Furthermore, marketing capabilities are positively associated with firm performance in highly competitive environments, whereas technological capabilities enhance performance in stable competitive environments.

Exercise interventions for the treatment of chronic low back pain: a systematic review and meta-analysis of randomised controlled trials

Abstract: Objective:To determine, for adults with chronic low back pain, which exercise interventions are the most effective at reducing pain compared to other treatments.Data sources:A search of MEDLINE, CINAHL, EMBASE, SPORTDiscus, PsycINFO and The Cochrane Library was conducted up to October 2014.Review methods:Databases were searched for published reports of randomised trials that investigated the treatment of chronic low back pain of non-specific origin with an exercise intervention. Two authors independently reviewed and selected relevant trials. Methodological quality was evaluated using the Downs and Black tool.Results:Forty-five trials met the inclusion criteria and thirty-nine were included in the meta-analysis. Combined meta-analysis revealed significantly lower chronic low back pain with intervention groups using exercise compared to a control group or other treatment group (Standard Mean Deviation (SMD) =-0.32, CI 95% -0.44 to -0.19, P<0.01). Separate exploratory subgroup analysis showed a significant ...

Jamming Attacks on Remote State Estimation in Cyber-Physical Systems: A Game-Theoretic Approach

Abstract: We consider security issues in remote state estimation of Cyber-Physical Systems (CPS). A sensor node communicates with a remote estimator through a wireless channel which may be jammed by an external attacker. With energy constraints for both the sensor and the attacker, the interactive decision making process of when to send and when to attack is studied. We formulate a game-theoretic framework and prove that the optimal strategies for both sides constitute a Nash equilibrium of a zero-sum game. To tackle the computation complexity issues, we present a constraint-relaxed problem and provide corresponding solutions using Markov chain theory.

Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

Abstract: General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

Predictive Optimal Switching Sequence Direct Power Control for Grid-Connected Power Converters

Abstract: Grid-connected power converters play a key role in several applications such as the integration of renewable energy sources and motor drives. For this reason, the development of high performance control strategies for this particular class of power converters has increasingly attracted the interest of both academic and industry researchers. This paper presents the predictive optimal switching sequence (OSS) direct power control (DPC) (OSS-DPC) algorithm for grid-connected converters. The OSS-DPC method belongs to the predictive-DPC family and provides the desired power references by calculating globally OSSs. To address computational and implementation issues, an efficient control algorithm, named reduced OSS-DPC, is introduced. The implementation of the proposed control strategy in a standard DSP is evaluated on a two-level power converter prototype working as a STATCOM. Experimental results show the algorithm's potential to provide high performance during both transient and steady states.

A systematic review and meta-analysis of social cognitive theory-based physical activity and/or nutrition behavior change interventions for cancer survivors.

Abstract: Little is known about how to improve and create sustainable lifestyle behaviors of cancer survivors. Interventions based on social cognitive theory (SCT) have shown promise. This review examined the effect of SCT-based physical activity and nutrition interventions that target cancer survivors and identified factors associated with their efficacy. A systematic search of seven databases identified randomized controlled trials that (i) targeted adult cancer survivors (any point from diagnosis); (ii) reported a primary outcome of physical activity, diet, or weight management; and (iii) included an SCT-based intervention targeting physical activity or diet. Qualitative synthesis and meta-analysis were conducted. Theoretical constructs and intervention characteristics were examined to identify factors associated with intervention efficacy. Eighteen studies (reported in 33 publications) met review inclusion criteria. Meta-analysis (n = 12) revealed a significant intervention effect for physical activity (standardized mean difference (SMD) = 0.33; P < 0.01). Most studies (six out of eight) that targeted dietary change reported significant improvements in at least one aspect of diet quality. No SCT constructs were associated with intervention effects. There were no consistent trends relating to intervention delivery method or whether the intervention targeted single or multiple behaviors. SCT-based interventions demonstrate promise in improving physical activity and diet behavior in cancer survivors, using a range of intervention delivery modes. Further work is required to understand how and why these interventions offer promise for improving behavior. SCT-based interventions targeting diet or physical activity are safe and result in meaningful changes to diet and physical activity behavior that can result in health improvements.

Point process models for presence-only analysis

Abstract: Summary Presence-only data are widely used for species distribution modelling, and point process regression models are a flexible tool that has considerable potential for this problem, when data arise as point events. In this paper, we review point process models, some of their advantages and some common methods of fitting them to presence-only data. Advantages include (and are not limited to) clarification of what the response variable is that is modelled; a framework for choosing the number and location of quadrature points (commonly referred to as pseudo-absences or ‘background points’) objectively; clarity of model assumptions and tools for checking them; models to handle spatial dependence between points when it is present; and ways forward regarding difficult issues such as accounting for sampling bias. Point process models are related to some common approaches to presence-only species distribution modelling, which means that a variety of different software tools can be used to fit these models, including maxent or generalised linear modelling software.