A self-assembling polycationic nanocarrier that exhibits exceptional gene transfection efficiency

The lack of an efficient and safe carrier is a major impediment in the field of gene therapy. Although gelatin (GT), a naturally derived polymer, is widely used in drug delivery applications, it is unable to bind DNA efficiently. In this study, a novel polycationic gene carrier was prepared by conjugation of low molecular weight polyethyleneimine (LPEI) with GT through 4-bromonaphthaleic anhydride as a coupling agent to avoid self crosslinking. Self-assembly of LPEI conjugated GT (GT-LPEI) with plasmid DNA (pDNA) yielded nanoparticles with high gene complexation ability to form similar to 250 nm cylindrical nanoparticles with a zeta potential of similar to 27 mV. GT-LPEI showed exceptionally high transfection efficiency (> 90%) in various mammalian cells including primary stem cells with minimal cytotoxicity. The transfection efficiency of GT-LPEI significantly surpassed that of many commercial reagents. The high gene transfection expression was confirmed in vivo. Thus, GT-LPEI is shown to be a promising nonviral carrier for potential use in gene therapy.

Self-Organized Criticality, Plasticity and Sensorimotor Coupling. Explorations with a Neurorobotic Model in a Behavioural Preference Task

During the last two decades, analysis of 1/f noise in cognitive science has led to a considerable progress in the way we understand the organization of our mental life. However, there is still a lack of specific models providing explanations of how 1/f noise is generated in coupled brain-body-environment systems, since existing models and experiments typically target either externally observable behaviour or isolated neuronal systems but do not address the interplay between neuronal mechanisms and sensorimotor dynamics. We present a conceptual model of a minimal neurorobotic agent solving a behavioural task that makes it possible to relate mechanistic (neurodynamic) and behavioural levels of description. The model consists of a simulated robot controlled by a network of Kuramoto oscillators with homeostatic plasticity and the ability to develop behavioural preferences mediated by sensorimotor patterns. With only three oscillators, this simple model displays self-organized criticality in the form of robust 1/f noise and a wide multifractal spectrum. We show that the emergence of self-organized criticality and 1/f noise in our model is the result of three simultaneous conditions: a) non-linear interaction dynamics capable of generating stable collective patterns, b) internal plastic mechanisms modulating the sensorimotor flows, and c) strong sensorimotor coupling with the environment that induces transient metastable neurodynamic regimes. We carry out a number of experiments to show that both synaptic plasticity and strong sensorimotor coupling play a necessary role, as constituents of self-organized criticality, in the generation of 1/f noise. The experiments also shown to be useful to test the robustness of 1/f scaling comparing the results of different techniques. We finally discuss the role of conceptual models as mediators between nomothetic and mechanistic models and how they can inform future experimental research where self-organized critically includes sensorimotor coupling among the essential interaction-dominant process giving rise to 1/f noise.

Low-threshold diode-pumped Yb3+, Na+: CaF2 self-Q-switched laser

For the first time to our knowledge, the laser performance of Yb3+, Na+-codoped CaF2 single crystals was demonstrated. Self-Q-switched laser operation at 1050nm was observed for 976 nm diode pumping at room temperature. On 5 W of incident power, the repetition rate and width of the self-Q-switched pulses reached 28 kHz and 1.5 mu s, respectively. A maximal slope efficiency of 20.3% and minimal threshold absorbed pump power of 30 mW were respectively achieved with different output couplers, showing the promising application of Yb3+, Na+-codoped CaF2 crystals as compact and efficient solid-state lasers. (C) 2005 Optical Society of America.

ARTMAP: Supervised Real-Time Learning and Classification of Nonstationary Data by a Self-Organizing Neural Network

This article introduces a new neural network architecture, called ARTMAP, that autonomously learns to classify arbitrarily many, arbitrarily ordered vectors into recognition categories based on predictive success. This supervised learning system is built up from a pair of Adaptive Resonance Theory modules (ARTa and ARTb) that are capable of self-organizing stable recognition categories in response to arbitrary sequences of input patterns. During training trials, the ARTa module receives a stream {a^(p)} of input patterns, and ARTb receives a stream {b^(p)} of input patterns, where b^(p) is the correct prediction given a^(p). These ART modules are linked by an associative learning network and an internal controller that ensures autonomous system operation in real time. During test trials, the remaining patterns a^(p) are presented without b^(p), and their predictions at ARTb are compared with b^(p). Tested on a benchmark machine learning database in both on-line and off-line simulations, the ARTMAP system learns orders of magnitude more quickly, efficiently, and accurately than alternative algorithms, and achieves 100% accuracy after training on less than half the input patterns in the database. It achieves these properties by using an internal controller that conjointly maximizes predictive generalization and minimizes predictive error by linking predictive success to category size on a trial-by-trial basis, using only local operations. This computation increases the vigilance parameter ρa of ARTa by the minimal amount needed to correct a predictive error at ARTb· Parameter ρa calibrates the minimum confidence that ARTa must have in a category, or hypothesis, activated by an input a^(p) in order for ARTa to accept that category, rather than search for a better one through an automatically controlled process of hypothesis testing. Parameter ρa is compared with the degree of match between a^(p) and the top-down learned expectation, or prototype, that is read-out subsequent to activation of an ARTa category. Search occurs if the degree of match is less than ρa. ARTMAP is hereby a type of self-organizing expert system that calibrates the selectivity of its hypotheses based upon predictive success. As a result, rare but important events can be quickly and sharply distinguished even if they are similar to frequent events with different consequences. Between input trials ρa relaxes to a baseline vigilance pa When ρa is large, the system runs in a conservative mode, wherein predictions are made only if the system is confident of the outcome. Very few false-alarm errors then occur at any stage of learning, yet the system reaches asymptote with no loss of speed. Because ARTMAP learning is self stabilizing, it can continue learning one or more databases, without degrading its corpus of memories, until its full memory capacity is utilized.

Mitigation of Fatigue Damage in Self-Healing Vascular Materials

The fatigue response of an epoxy matrix containing vasculature for the delivery of liquid healing agents is investigated. The release of a rapidly curing, two-part epoxy healing chemistry into the wake of a propagating crack reduces the rate of crack extension by shielding the crack tip from the full range of applied stress intensity factor. Crack propagation is studied for a variety of loading conditions, with the maximum applied stress intensity factor ranging from 62 to 84% of the quasi-static fracture toughness of the material. At the highest level of applied load, the rate of mechanical damage is so fast that the healing agents do not fully mix and polymerize, and the effect of healing is minimal. The self-healing response is most effective at impeding the slower propagating cracks, with complete crack arrest occurring at the lowest level of applied load, and reductions of 79–84% in the rate of crack extension at intermediate loads.

Adaptive self-calibrating image rejection receiver

An adaptive self-calibrating image rejection receiver is described, containing a modified Weaver image rejection mixer and a Digital Image Rejection Processor (DIRP). The blind source-separation-based DIRP eliminates the I/Q errors improving the Image Rejection Ratio (IRR) without the need for trimming or use of power-hungry discrete components. Hardware complexity is minimal, requiring only two complex coefficients; hence it can be easily integrated into the signal processing path of any receiver. Simulation results show that the proposed approach achieves 75-97 dB of IRR.

Self-organization for scheduling in agile manufacturing

Agility refers to the manufacturing system ability to rapidly adapt to market and environmental changes in efficient and cost-effective ways. This paper addresses the development of self-organization methods to enhance the operations of a scheduling system, by integrating scheduling system, configuration and optimization into a single autonomic process requiring minimal manual intervention to increase productivity and effectiveness while minimizing complexity for users. We intend to conceptualize real manufacturing systems as interacting autonomous entities in order to build future Decision Support Systems (DSS) for Scheduling in agile manufacturing environments.

Effort, reward and self-reported mental health: a simulation study on negative affectivity bias.

Background : In the present article, we propose an alternative method for dealing with negative affectivity (NA) biases in research, while investigating the association between a deleterious psychosocial environment at work and poor mental health. First, we investigated how strong NA must be to cause an observed correlation between the independent and dependent variables. Second, we subjectively assessed whether NA can have a large enough impact on a large enough number of subjects to invalidate the observed correlations between dependent and independent variables.Methods : We simulated 10,000 populations of 300 subjects each, using the marginal distribution of workers in an actual population that had answered the Siegrist's questionnaire on effort and reward imbalance (ERI) and the General Health Questionnaire (GHQ).Results : The results of the present study suggested that simulated NA has a minimal effect on the mean scores for effort and reward. However, the correlations between the effort and reward imbalance (ERI) ratio and the GHQ score might be important, even in simulated populations with a limited NA.Conclusions : When investigating the relationship between the ERI ratio and the GHQ score, we suggest the following rules for the interpretation of the results: correlations with an explained variance of 5% and below should be considered with caution; correlations with an explained variance between 5% and 10% may result from NA, although this effect does not seem likely; and correlations with an explained variance of 10% and above are not likely to be the result of NA biases. [Authors]

A model for self-directed problem-based learning for renal therapeutics

Objective To introduce a new approach to problem-based learning (PBL) for self-directed learning in renal therapeutics. Design This 5-week course, designed for large student cohorts using minimal teaching resources, was based on a series of case studies and subsequent pharmaceutical care plans, followed by intensive and regular feedback from the instructor. Assessment Assessment of achievement of the learning outcomes was based on weekly-graded care plans and peer review assessment, allowing each student to judge the contributions of each group member and their own, along with a written case-study based examination. The pharmaceutical care plan template, designed using a “tick-box” system, significantly reduced staff time for feedback and scoring. Conclusion The proposed instructional model achieved the desired learning outcomes with appropriate student feedback, while promoting skills that are essential for the students' future careers as health care professionals.

Triggering Solar-Powered Vehicle Activated Signs using Self Organising Maps with K-means

Solar-powered vehicle activated signs (VAS) are speed warning signs powered by batteries that are recharged by solar panels. These signs are more desirable than other active warning signs due to the low cost of installation and the minimal maintenance requirements. However, one problem that can affect a solar-powered VAS is the limited power capacity available to keep the sign operational. In order to be able to operate the sign more efficiently, it is proposed that the sign be appropriately triggered by taking into account the prevalent conditions. Triggering the sign depends on many factors such as the prevailing speed limit, road geometry, traffic behaviour, the weather and the number of hours of daylight. The main goal of this paper is therefore to develop an intelligent algorithm that would help optimize the trigger point to achieve the best compromise between speed reduction and power consumption. Data have been systematically collected whereby vehicle speed data were gathered whilst varying the value of the trigger speed threshold. A two stage algorithm is then utilized to extract the trigger speed value. Initially the algorithm employs a Self-Organising Map (SOM), to effectively visualize and explore the properties of the data that is then clustered in the second stage using K-means clustering method. Preliminary results achieved in the study indicate that using a SOM in conjunction with K-means method is found to perform well as opposed to direct clustering of the data by K-means alone. Using a SOM in the current case helped the algorithm determine the number of clusters in the data set, which is a frequent problem in data clustering.

Indigenous peoples, self-determination and international law

The article examines the re-emergence of indigenous rights in contemporary international law in the context of worldwide agitation by indigenous peoples for the adoption by the United Nations of a Declaration on the Rights of Indigenous Peoples. Two approaches to the protection of indigenous rights are considered: a minimal one that relies on existing human rights conventions, and an inspirational one that seeks a Declaration negotiated in partnership with states willing to recognise indigenous autonomy. Attention is given to judicial recognition of the right to self-determination as a right of free choice, and to the distinction between minority rights and indigenous autonomy. The importance of defining indigenous self-determination in a positive way is emphasised, and prospects for a new UN permanent indigenous forum overcoming the stalemate about indigenous rights are reviewed in terms of the need for greater dialogue.

The influence of object-image velocity change on perceived heading in minimal environments

When human observers move forward and rotate their eyes, a complex pattern of light flows across the retina. This pattern is referred to as retinal flow. A model has been proposed to explain how humans perceive their direction of self-movement (or heading) from (1) static depth, (2) direction of image motion, and (3) whether image velocity undergoes acceleration or deceleration (Wang & Cutting, 1999). However, findings from past research in which sparse or minimalist stimuli were used have suggested that not all of the information to which participants are sensitive is captured within the scope of this model. In particular it has been suggested that the magnitude or size of image velocity change may be of significance beyond simply whether image velocity could be categorized as speeding up (i.e., accelerating) or slowing down (i.e., decelerating). In two experiments, the influence of this factor on heading judgments under minimal conditions was investigated. Evidence was found in support of the idea that the rate of image velocity change can influence judgments of the direction of self-movement in minimalist conditions.

The extent and breadth of benefits from participating in chronic disease self-management courses: a national patient-reported outcomes survey

Objective
To quantify the benefits that people receive from participating in self-management courses and identify subgroups that benefit most.

Methods
People with a wide range of chronic conditions attending self-management courses (N = 1341 individuals) were administered the Health Education Impact Questionnaire (heiQ). Baseline and follow-up data were collected resulting in 842 complete responses. Outcomes were categorized as substantial improvement (effect size, ES ≥ 0.5), minimal/no change (ES −0.49 to 0.49) and substantial decline (ES ≤ −0.5).

Results
On average, one third of participants reported substantial benefits at the end of a course and this ranged from 49% in the heiQ subscale Skill and technique acquisition to 27% in the heiQ subscale Health service navigation. Stratification by gender, age and education showed that younger participants were more likely to benefit, particularly young women. No further subgroup differences were observed.

Conclusion
While the well-being of people with chronic diseases tends to decline, about one third of participants from a wide range of backgrounds show substantial improvements in a range of skills that enable them to self-manage.

Practice implications
These data support the application of self-management courses indicating that they are a useful adjunct to usual care for a modest proportion of attendees.

Can a disease-specific education program augment self-management skills and improve Health-Related Quality of Life in people with hip or knee osteoarthritis?

Background: Patient education and self-management programs are offered in many countries to people with chronic conditions such as osteoarthritis (OA). The most well-known is the disease-specific Stanford Arthritis Self-Management Program (ASMP). While Australian and international clinical guidelines promote the concept of self-management for OA, there is currently little evidence to support the use of the ASMP. Several meta-analyses have reported that arthritis self-management programs had minimal or no effect on reducing pain and disability. However, previous studies have had methodological shortcomings including the use of outcome measures which do not accurately reflect program goals. Additionally, limited cost-effectiveness analyses have been undertaken and the cost-utility of the program has not been explored.

Methods/design: This study is a randomised controlled trial to determine the efficacy (in terms of Health-Related Quality of Life and self-management skills) and cost-utility of a 6-week group-based Stanford ASMP for people with hip or knee OA.

Six hundred participants referred to an orthopaedic surgeon or rheumatologist for hip or knee OA will be recruited from outpatient clinics at 2 public hospitals and community-based private practices within 2 private hospital settings in Victoria, Australia. Participants must be 18 years or over, fluent in English and able to attend ASMP sessions. Exclusion criteria include cognitive dysfunction, previous participation in self-management programs and placement on a waiting list for joint replacement surgery or scheduled joint replacement.

Eligible, consenting participants will be randomised to an intervention group (who receive the ASMP and an arthritis self-management book) or a control group (who receive the book only). Follow-up will be at 6 weeks, 3 months and 12 months using standardised self-report measures. The primary outcome is Health-Related Quality of Life at 12 months, measured using the Assessment of Quality of Life instrument. Secondary outcome measures include the Health Education Impact Questionnaire, Western Ontario and McMaster Universities Osteoarthritis Index (pain subscale and total scores), Kessler Psychological Distress Scale and the Hip and Knee Multi-Attribute Priority Tool. Cost-utility analyses will be undertaken using administrative records and self-report data. A subgroup of 100 participants will undergo qualitative interviews to explore the broader potential impacts of the ASMP.

Discussion: Using an innovative design combining both quantitative and qualitative components, this project will provide high quality data to facilitate evidence-based recommendations regarding the ASMP.

Social control, self-control and psychosocial problems in adolescent males

‘Psychosocial problems’ are psychological problems that are regarded as resulting from the interaction between the adaptive capacities of individuals and the demands of their physical and social environments. Many different factors have been theoretically proposed, and empirically established, as predictors of a range of psychosocial problems in adolescents. However, a problem exists in that this literature appears to lack an integrative framework that has validity across the range of problems that are observed. The purpose of the current research is to propose and test a model that draws together three clusters of factors that are useful in predicting the incidence of adolescent psychosocial problems. These are family structural background factors, family functioning variables and control beliefs. Data were collected from 155 adolescent males aged between 12 and 19 by a single concurrent and retrospective self-report questionnaire. This included data about the respondent (age, involvements with mental health or juvenile justice agencies) and family structural background factors (days per week worked by mother/father, occupational status for mother/father, residential mobility, number of persons in the family home). The questionnaire also incorporated the Parental Bonding Instrument (Parker, Tupling & Brown, 1979) to quantify the levels of perceived parental care and overprotection, and an adaptation of the Parental Discipline Style Scale (Shaw & Scott, 1991), to assess punitive, love withdrawing and inductive discipline practices. In addition, the (Low) Self-control Scale (Grasmick, Tittle, Bursick & Arneklev, 1993) and the Locus of Control of Behaviour Scale (Craig, Franklin, & Andrews, 1984) were used to collect data concerning adolescents’ perceived behavioural self-control and locus of control. Finally, selected sub-scales of the Child Behavior Checklist Youth Self-Report (Achenbach, 1991b) were used to collect data on the incidence of social withdrawal, somatisation, anxiety and depression, aggression and delinquency among the respondents, and in aggregated form, the incidence of ‘total problems’ and internalising and externalising behaviours. Results indicated family structural background factors, family functioning variables and control beliefs possess limited predicted validity and that the usefulness of the proposed model varies between specific psychosocial problems. Family functioning variables were generally stronger predictors than family structural background factors, particularly for internalising behaviours. Of these, levels of parental care and overprotection were generally the strongest predictors. Perceived self-control and locus of control were also generally strong predictors, but were particularly powerful with respect to externalising behaviours. The strength of predictive relationships was observed to vary between specific internalising and externalising behaviours, suggesting that individual difference variables not assessed in the current research were differentially influential. Finally, the parental and individual characteristics that predicted maximal levels of adjustment (defined in terms of minimal levels of internalising and externalising behaviours) were explored and the correlates of various parenting style typologies (Parker et al., 1979) were investigated. These results strongly confirmed the importance of family functioning and control beliefs with respect to the prediction of internalising, externalising and well-adjusted behaviours. In all analyses, substantial proportions of the variance in the incidence of problem behaviours remain unexplained. The findings are examined in relation to previous research focused on (familial) social control and (individual) self-control with respect to psychosocial problems in adolescents. In addition, methodological considerations are discussed and the implications of the findings for clinical and community interventions to address problem behaviours, and for further study, are explored.