164 research outputs found
The Influence of Low-Energy Algorithms on Steganography
Recent advances in pseudorandom archetypes and client- server methodologies have introduced a domain for e-business. Given the current status of concurrent configurations, theorists daringly desire the evaluation of e-business, demonstrates the private importance of steganography. Our focus in our research is not on whether lambda calculus and 802.11b are often incompatible, but rather on exploring a novel methodology for the refinement of forward-error correction (Gerocomy)
A randomised controlled trial to prevent hospital readmissions and loss of functional ability in high risk older adults: a study protocol
Background Older people have higher rates of hospital admission than the general population and higher rates of readmission due to complications and falls. During hospitalisation, older people experience significant functional decline which impairs their future independence and quality of life. Acute hospital services comprise the largest section of health expenditure in Australia and prevention or delay of disease is known to produce more effective use of services. Current models of discharge planning and follow-up care, however, do not address the need to prevent deconditioning or functional decline. This paper describes the protocol of a randomised controlled trial which aims to evaluate innovative transitional care strategies to reduce unplanned readmissions and improve functional status, independence, and psycho-social well-being of community-based older people at risk of readmission. Methods/Design The study is a randomised controlled trial. Within 72 hours of hospital admission, a sample of older adults fitting the inclusion/exclusion criteria (aged 65 years and over, admitted with a medical diagnosis, able to walk independently for 3 meters, and at least one risk factor for readmission) are randomised into one of four groups: 1) the usual care control group, 2) the exercise and in-home/telephone follow-up intervention group, 3) the exercise only intervention group, or 4) the in-home/telephone follow-up only intervention group. The usual care control group receive usual discharge planning provided by the health service. In addition to usual care, the exercise and in-home/telephone follow-up intervention group receive an intervention consisting of a tailored exercise program, in-home visit and 24 week telephone follow-up by a gerontic nurse. The exercise only and in-home/telephone follow-up only intervention groups, in addition to usual care receive only the exercise or gerontic nurse components of the intervention respectively. Data collection is undertaken at baseline within 72 hours of hospital admission, 4 weeks following hospital discharge, 12 weeks following hospital discharge, and 24 weeks following hospital discharge. Outcome assessors are blinded to group allocation. Primary outcomes are emergency hospital readmissions and health service use, functional status, psychosocial well-being and cost effectiveness. Discussion The acute hospital sector comprises the largest component of health care system expenditure in developed countries, and older adults are the most frequent consumers. There are few trials to demonstrate effective models of transitional care to prevent emergency readmissions, loss of functional ability and independence in this population following an acute hospital admission. This study aims to address that gap and provide information for future health service planning which meets client needs and lowers the use of acute care services
Proportions of Convective and Stratiform Precipitation Revealed in Water Isotope Ratios
Tropical and midlatitude precipitation is fundamentally of two types, spatially-limited and high-intensity convective or widespread and lower-intensity stratiform, owing to differences in vertical air motions and microphysical processes governing rain formation. These processes are difficult to observe or model and precipitation partitioning into rain types is critical for understanding how the water cycle responds to climate changes. Here, we combine two independent data sets – convective and stratiform precipitation fractions, derived from the Tropical Rainfall Measuring Mission satellite or synoptic cloud observations, and stable isotope and tritium compositions of surface precipitation, derived from a global network – to show that isotope ratios reflect rain type proportions and are negatively correlated with stratiform fractions. Condensation and riming associated with boundary layer moisture produces higher isotope ratios in convective rain, along with higher tritium when riming in deep convection occurs with entrained air at higher altitudes. Based on our data, stable isotope ratios can be used to monitor changes in the character of precipitation in response to periodic variability or changes in climate. Our results also provide observational constraints for an improved simulation of convection in climate models and a better understanding of isotope variations in proxy archives, such as speleothems and tropical ice
Identification of CD4+ T Cell Epitopes in C. burnetii Antigens Targeted by Antibody Responses
Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes acute Q fever and chronic infections in humans. A killed, whole cell vaccine is efficacious, but vaccination can result in severe local or systemic adverse reactions. Although T cell responses are considered pivotal for vaccine derived protective immunity, the epitope targets of CD4+ T cell responses in C. burnetii vaccination have not been elucidated. Since mapping CD4+ epitopes in a genome with over 2,000 ORFs is resource intensive, we focused on 7 antigens that were known to be targeted by antibody responses. 117 candidate peptides were selected from these antigens based on bioinformatics predictions of binding to the murine MHC class II molecule H-2 IAb. We screened these peptides for recognition by IFN-γ producing CD4+ T cell in phase I C. burnetii whole cell vaccine (PI-WCV) vaccinated C57BL/6 mice and identified 8 distinct epitopes from four different proteins. The identified epitope targets account for 8% of the total vaccination induced IFN-γ producing CD4+ T cells. Given that less than 0.4% of the antigens contained in C. burnetii were screened, this suggests that prioritizing antigens targeted by antibody responses is an efficient strategy to identify at least a subset of CD4+ targets in large pathogens. Finally, we examined the nature of linkage between CD4+ T cell and antibody responses in PI-WCV vaccinated mice. We found a surprisingly non-uniform pattern in the help provided by epitope specific CD4+ T cells for antibody production, which can be specific for the epitope source antigen as well as non-specific. This suggests that a complete map of CD4+ response targets in PI-WCV vaccinated mice will likely include antigens against which no antibody responses are made
Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection
Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene expression analyses in general, but not by the identification of specific regulatory elements responsible for changes in transcription and phenotype. To identify the genetic source of regulatory differences, we mapped DNaseI hypersensitive (DHS) sites, which mark all types of active gene regulatory elements, genome-wide in the same cell type isolated from human, chimpanzee, and macaque. Most DHS sites were conserved among all three species, as expected based on their central role in regulating transcription. However, we found evidence that several hundred DHS sites were gained or lost on the lineages leading to modern human and chimpanzee. Species-specific DHS site gains are enriched near differentially expressed genes, are positively correlated with increased transcription, show evidence of branch-specific positive selection, and overlap with active chromatin marks. Species-specific sequence differences in transcription factor motifs found within these DHS sites are linked with species-specific changes in chromatin accessibility. Together, these indicate that the regulatory elements identified here are genetic contributors to transcriptional and phenotypic differences among primate species
Clinical Utility of Random Anti–Tumor Necrosis Factor Drug–Level Testing and Measurement of Antidrug Antibodies on the Long-Term Treatment Response in Rheumatoid Arthritis
Objective: To investigate whether antidrug antibodies and/or drug non-trough levels predict the long-term treatment response in a large cohort of patients with rheumatoid arthritis (RA) treated with adalimumab or etanercept and to identify factors influencing antidrug antibody and drug levels to optimize future treatment decisions. Methods: A total of 331 patients from an observational prospective cohort were selected (160 patients treated with adalimumab and 171 treated with etanercept). Antidrug antibody levels were measured by radioimmunoassay, and drug levels were measured by enzyme-linked immunosorbent assay in 835 serial serum samples obtained 3, 6, and 12 months after initiation of therapy. The association between antidrug antibodies and drug non-trough levels and the treatment response (change in the Disease Activity Score in 28 joints) was evaluated. Results: Among patients who completed 12 months of followup, antidrug antibodies were detected in 24.8% of those receiving adalimumab (31 of 125) and in none of those receiving etanercept. At 3 months, antidrug antibody formation and low adalimumab levels were significant predictors of no response according to the European League Against Rheumatism (EULAR) criteria at 12 months (area under the receiver operating characteristic curve 0.71 [95% confidence interval (95% CI) 0.57, 0.85]). Antidrug antibody–positive patients received lower median dosages of methotrexate compared with antidrug antibody–negative patients (15 mg/week versus 20 mg/week; P = 0.01) and had a longer disease duration (14.0 versus 7.7 years; P = 0.03). The adalimumab level was the best predictor of change in the DAS28 at 12 months, after adjustment for confounders (regression coefficient 0.060 [95% CI 0.015, 0.10], P = 0.009). Etanercept levels were associated with the EULAR response at 12 months (regression coefficient 0.088 [95% CI 0.019, 0.16], P = 0.012); however, this difference was not significant after adjustment. A body mass index of ≥30 kg/m2 and poor adherence were associated with lower drug levels. Conclusion: Pharmacologic testing in anti–tumor necrosis factor–treated patients is clinically useful even in the absence of trough levels. At 3 months, antidrug antibodies and low adalimumab levels are significant predictors of no response according to the EULAR criteria at 12 months
Design principles in housing for people with complex physical and cognitive disability: towards an integrated framework for practice
To develop a research-based environmental framework to guide the design and construction of suitable residential dwellings for individuals with complex disability. An environmental approach to housing design and development recognises that there are physical, psychological and social components relating to housing design, dwelling location and the neighbourhood context, and that these elements interact to affect the physical, psychological, and social wellness of individuals. Following theoretical review and synthesis, a comprehensive set of design features that are conducive to residents’ wellness and quality of life are described. It is clear that housing design and development for people with complex disability ought to consider the physical, social, natural, symbolic, and care environment in relation to housing design, dwelling location, and the neighbourhood context for improved housing outcomes. An integrated housing design and development framework is presented. It is hoped this practical matrix/evaluative tool will inform future inclusive housing design and development decisions in Australia and internationally. The application of this framework is especially relevant to political climates striving to achieve design innovation to increase housing choice for people with complex disability
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