Potential of lipid core peptide technology as a novel self-adjuvanting vaccine delivery system for multiple different synthetic peptide immunogens

This study demonstrates the effectiveness of a novel self-adjuvanting vaccine delivery system for multiple different synthetic peptide immunogens by use of lipid core peptide (LCP) technology. An LCP formulation incorporating two different protective epitopes of the surface antiphagocytic M protein of group A streptococci (GAS)-the causative agents of rheumatic fever and subsequent rheumatic heart disease-was tested in a murine parenteral immunization and GAS challenge model. Mice were immunized with the LCP-GAS formulation, which contains an M protein amino-terminal type-specific peptide sequence (8830) in combination with a conserved non-host-cross-reactive carboxy-terminal C-region peptide sequence (J8) of the M protein. Our data demonstrated immunogenicity of the LCP-8830-J8 formulation in B10.BR mice when coadministered in complete Freund's adjuvant and in the absence of a conventional adjuvant. In both cases, immunization led to induction of high-titer GAS peptide-specific serum immunoglobulin G antibody responses and induction of highly opsonic antibodies that did not cross-react with human heart tissue proteins. Moreover, mice were completely protected from GAS infection when immunized with LCP-8830-J8 in the presence or absence of a conventional adjuvant. Mice were not protected, however, following immunization with an LCP formulation containing a control peptide from a Schistosoma sp. These data support the potential of LCP technology in the development of novel self-adjuvanting multi-antigen component vaccines and point to the potential application of this system in the development of human vaccines against infectious diseases.

Modelling the population cost-effectiveness of current and evidence-based optimal treatment for anxiety disorders

Background. The present paper describes a component of a large Population cost-effectiveness study that aimed to identify the averted burden and economic efficiency of current and optimal treatment for the major mental disorders. This paper reports on the findings for the anxiety disorders (panic disorder/agoraphobia, social phobia, generalized anxiety disorder, post-traumatic stress disorder and obsessive-compulsive disorder). Method. Outcome was calculated as averted 'years lived with disability' (YLD), a population summary measure of disability burden. Costs were the direct health care costs in 1997-8 Australian dollars. The cost per YLD averted (efficiency) was calculated for those already in contact with the health system for a mental health problem (current care) and for a hypothetical optimal care package of evidence-based treatment for this same group. Data sources included the Australian National Survey of Mental Health and Well-being and published treatment effects and unit costs. Results. Current coverage was around 40% for most disorders with the exception of social phobia at 21%. Receipt of interventions consistent with evidence-based care ranged from 32% of those in contact with services for social phobia to 64% for post-traumatic stress disorder. The cost of this care was estimated at $400 million, resulting in a cost per YLD averted ranging from $7761 for generalized anxiety disorder to $34 389 for panic/agoraphobia. Under optimal care, costs remained similar but health gains were increased substantially, reducing the cost per YLD to < $20 000 for all disorders. Conclusions. Evidence-based care for anxiety disorders would produce greater population health gain at a similar cost to that of current care, resulting in a substantial increase in the cost-effectiveness of treatment.

A cost-effectiveness analysis of two rehabilitation support services for women with breast cancer

The purpose of this research was to estimate the cost-effectiveness of two rehabilitation interventions for breast cancer survivors, each compared to a population-based, non-intervention group (n = 208). The two services included an early home-based physiotherapy intervention (DAART, n = 36) and a group-based exercise and psychosocial intervention (STRETCH, n = 31). A societal perspective was taken and costs were included as those incurred by the health care system, the survivors and community. Health outcomes included: (a) 'rehabilitated cases' based on changes in health-related quality of life between 6 and 12 months post-diagnosis, using the Functional Assessment of Cancer Therapy - Breast Cancer plus Arm Morbidity (FACT-B+4) questionnaire, and (b) quality-adjusted life years (QALYs) using utility scores from the Subjective Health Estimation (SHE) scale. Data were collected using self-reported questionnaires, medical records and program budgets. A Monte-Carlo modelling approach was used to test for uncertainty in cost and outcome estimates. The proportion of rehabilitated cases was similar across the three groups. From a societal perspective compared with the non-intervention group, the DAART intervention appeared to be the most efficient option with an incremental cost of $1344 per QALY gained, whereas the incremental cost per QALY gained from the STRETCH program was $14,478. Both DAART and STRETCH are low-cost, low-technological health promoting programs representing excellent public health investments.

Effectiveness of hospital-based smoking cessation

Study objectives: Smoking cessation for current smokers is a health-care imperative. It is not clear which approaches to smoking cessation are the most effective in the hospital setting and which factors predict long-term abstinence. We hypothesized that a hospital-based smoking cessation program involving behavioral modification and support would provide an effective intervention for smoking cessation. Design: Prospective cohort study. Setting: Smoking cessation clinics in a tertiary referral, cardiothoracic hospital. Patients or participants: Two hundred forty-three smokers and 187 never-smoker control subjects. Interventions: Smokers underwent specific sessions of individual counseling on behavioral modification, including written information, advice about quit aids, and support during the quit attempt. Abstinence was confirmed by exhaled carbon monoxide measurements. Measurements and results: Compared to never-smoker control subjects, smokers were more likely to have grown up with a smoking father or siblings, and to currently live or socialize with other smokers. Two hundred sixteen smokers attended at least two sessions of the smoking cessation program. Of these, 25% were unavailable for follow-up at 12 months and were assumed to be smoking. The point prevalence abstinence rate at 12 months was 32%. Independent factors associated with abstinence at 12 months were self-belief in quitting ability, having a heart condition, growing up without siblings who smoked, and increasing number of pack-years. Conclusions: This prospective study has demonstrated that this hospital-based smoking cessation program was as effective as programs in other settings. Social and psychological factors were associated with a greater chance of abstinence.

Pollination of Australian Macrozamia cycads (Zamiaceae): Effectiveness and behavior of specialist vectors in a dependent mutualism

Complementary field and laboratory tests confirmed and quantified the pollination abilities of Tranes sp. weevils and Cycadothrips chadwicki thrips, specialist insects of their respective cycad hosts, Macrozamia machinii and M. lucida. No agamospermous seeds were produced when both wind and insects were excluded from female cones; and the exclusion of wind-vectored pollen alone did not eliminate seed set, because insects were able to reach the cone. Based on enclosure pollination tests, each weevil pollinates an average 26.2 ovules per cone and each thrips 2.4 ovules per cone. These pollinators visited similar numbers of ovules per cone in fluorescent dye tests that traced insect movement through cones. Fluorescent dye granules deposited by Cycadothrips were concentrated around the micropyle of each visited ovule, the site of pollen droplet release, where pollen must be deposited to achieve pollination. In contrast, Tranes weevils left dye scattered on different areas of each visited ovule, indicating that chance plays a greater role in this system. Each weevil and 25 thrips delivered 6.2 and 5.2 pollen grains, respectively, on average, to each visited ovule per cone, based on examination of dissected pollen canals. In sum, the pollination potential of 25 Cycadothrips approximates that of one Tranes weevil.

A cognitive genetic algorithm for power distribution system planning

Power systems are large scale nonlinear systems with high complexity. Various optimization techniques and expert systems have been used in power system planning. However, there are always some factors that cannot be quantified, modeled, or even expressed by expert systems. Moreover, such planning problems are often large scale optimization problems. Although computational algorithms that are capable of handling large dimensional problems can be used, the computational costs are still very high. To solve these problems, in this paper, investigation is made to explore the efficiency and effectiveness of combining mathematic algorithms with human intelligence. It had been discovered that humans can join the decision making progresses by cognitive feedback. Based on cognitive feedback and genetic algorithm, a new algorithm called cognitive genetic algorithm is presented. This algorithm can clarify and extract human's cognition. As an important application of this cognitive genetic algorithm, a practical decision method for power distribution system planning is proposed. By using this decision method, the optimal results that satisfy human expertise can be obtained and the limitations of human experts can be minimized in the mean time.

An Internet-based telerehabilitation system for the assessment of motor speech disorders: A pilot study

Purpose: This pilot study explored the feasibility and effectiveness of an Internet-based telerehabilitation application for the assessment of motor speech disorders in adults with acquired neurological impairment. Method: Using a counterbalanced, repeated measures research design, 2 speech-language pathologists assessed 19 speakers with dysarthria on a battery of perceptual assessments. The assessments included a 19-item version of the Frenchay Dysarthria Assessment (FDA; P. Enderby, 1983), the Assessment of Intelligibility of Dysarthric Speech (K. M. Yorkston & D. R. Beukelman, 1981), perceptual analysis of a speech sample, and an overall rating of severity of the dysarthria. One assessment was conducted in the traditional face-to-face manner, whereas the other assessment was conducted using an online, custom-built telerehabilitation application. This application enabled real-time videoconferencing at 128 kb/s and the transfer of store-and-forward audio and video data between the speaker and speech-language pathologist sites. The assessment methods were compared using the J.M.Bland and D.G.Altman (1986, 1999) limits-of-agreement method and percentage level of agreement between the 2 methods. Results: Measurements of severity of dysarthria, percentage intelligibility in sentences, and most perceptual ratings made in the telerehabilitation environment were found to fall within the clinically acceptable criteria. However, several ratings on the FDA were not comparable between the environments, and explanations for these results were explored. Conclusions: The online assessment of motor speech disorders using an Internet-based telerehabilitation system is feasible. This study suggests that with additional refinement of the technology and assessment protocols, reliable assessment of motor speech disorders over the Internet is possible. Future research methods are outlined.

Incremental cost-effectiveness of exercise echocardiography vs. SPECT imaging for the evaluation of stable chest pain

Aims Technological advances in cardiac imaging have led to dramatic increases in test utilization and consumption of a growing proportion of cardiovascular healthcare costs. The opportunity costs of strategies favouring exercise echocardiography or SPECT imaging have been incompletely evaluated. Methods and results We examined prognosis and cost-effectiveness of exercise echocardiography (n=4884) vs. SPECT (n=4637) imaging in stable, intermediate risk, chest pain patients. Ischaemia extent was defined as the number of vascular territories with echocardiographic wall motion or SPECT perfusion abnormalities. Cox proportional hazard models were employed to assess time to cardiac death or myocardial infarction (MI). Total cardiovascular costs were summed (discounted and inflation-corrected) throughout follow-up. A cost-effectiveness ratio = 2% annual event risk), SPECT ischaemia was associated with earlier and greater utilization of coronary revascularization (P < 0.0001) resulting in an incremental cost-effectiveness ratio of $32 381/LYS. Conclusion Health care policies aimed at allocating limited resources can be effectively guided by applying clinical and economic outcomes evidence. A strategy aimed at cost-effective testing would support using echocardiography in low-risk patients with suspected coronary disease, whereas those higher risk patients benefit from referral to SPECT imaging.

Integrated power scheme simulator for human-system integration studies

We present a simulator of a hydropower company’s view of its scheme, and its broader market and network context, which has been developed to evaluate advanced displays for control room operations. Although simplified, the simulator captures all the main aspects of scheme operations. The simulator allows controlled studies to be performed that test the effectiveness of current vs advanced display concepts under normal vs unexpected operating conditions that can be scripted into the simulator.

Internet-based indicated prevention for panic disorder: An effectiveness trial in primary care

Previous studies have shown that an internet delivered indicated prevention program for panic disorder can be effective. However, those studies were done with select populations. Most individuals who are at risk for panic disorder present to hospital emergency rooms and primary care settings. This paper reports on a study currently being undertaken in Scotland where the program is being trialed in primary care. The intervention and experimental design will be described. However the key research question is whether General Practitioners will make use of the internet-based intervention system. Preliminary results will be reported. The results of the study will have implications for the way that primary care is recruited into the prevention of mental health problems.

Effectiveness of evaporative cooling of beef cattle housed in confinement

Eighteen Angus steers exposed to high heat load conditions were used to assess the effectiveness of four spray cooling systems, on reducing the effects of heat load, the impact on microclimate and water usage. The steers were housed in groups of nine in a fully enclosed shed and were exposed to high heat load conditions for four days. The cooling systems used were water applied via a hose, via overhead sprinklers, via sprinklers at leg height and via misters. The water used was approximately 31 oC and contained 3% NaCl. Fans were used to ensure adequate air movement over the cattle. The animal parameters measured were feed intake, respiration rate, panting score and behaviour. Climatic factors were ambient temperature and wet bulb temperature. Ammonia levels were also measured. The hose, overhead sprinklers and misting were successful in reducing heat load on the cattle. The leg wetting system did not work because the dominant cattle blocked access to the sprinklers. The misting system used the most water (5483 L) and the hose the least (845 L). The application of water had minor impacts on wet bulb temperature, but resulted in significant reductions in dry bulb temperatures.

Optimum switching point assessment of parallel braking resistor and serial current limiter for power system stability enhancement

A new control algorithm using parallel braking resistor (BR) and serial fault current limiter (FCL) for power system transient stability enhancement is presented in this paper. The proposed control algorithm can prevent transient instability during first swing by immediately taking away the transient energy gained in faulted period. It can also reduce generator oscillation time and efficiently make system back to the post-fault equilibrium. The algorithm is based on a new system energy function based method to choose optimal switching point. The parallel BR and serial FCL resistor can be switched at the calculated optimal point to get the best control result. This method allows optimum dissipation of the transient energy caused by disturbance so to make system back to equilibrium in minimum time. Case studies are given to verify the efficiency and effectiveness of this new control algorithm.