Altered serological and cellular reactivity to H-2 antigens after target cell infection with vaccinia virus

MICE generate cytotoxic T lymphocytes (CTL) which are able to lyse virus infected target cells in vitro after infection with lymphocytic choriomeningitis virus (LCMV) and pox-viruses1−3. CTL kill syngeneic and semiallogenic infected cells but not allogenic infected targets. Target cell lysis in these systems seems to be restricted by H-2 antigens, especially by the K or D end of the major histocompatibility complex (MHC). In experiments where virus specific sensitised lymphocytes kill virus infected allogenic target cells4 the effector lymphocytes have not been characterised exactly. Recent investigations suggest that the active cell in this assay, at least in the measles infection, is a non-thymus derived cell (H. Kreth, personal communication). An H-2 restriction of cell mediated cytolysis (CMC) to trinitrophenol (TNP)-modified lymphocytes has also been described5. Zinkernagel and Doherty6 postulated that the CTL is directed against syngeneic H-2 antigens and viral antigens and they suggested an alteration of H-2 induced by the LCMV infection. Earlier7 we found a close topological relationship between H-2 antigens and the target antigen(s) responsible for CMC in the vaccinia system. Here we report experiments which were carried out to prove alteration of H-2 after infection of L-929 fibroblasts with vaccinia virus

Testing the paradox of enrichment along a land use gradient in a multitrophic aboveground and belowground community

In the light of ongoing land use changes, it is important to understand how multitrophic communities perform at different land use intensities. The paradox of enrichment predicts that fertilization leads to destabilization and extinction of predator-prey systems. We tested this prediction for a land use intensity gradient from natural to highly fertilized agricultural ecosystems. We included multiple aboveground and belowground trophic levels and land use-dependent searching efficiencies of insects. To overcome logistic constraints of field experiments, we used a successfully validated simulation model to investigate plant responses to removal of herbivores and their enemies. Consistent with our predictions, instability measured by herbivore-induced plant mortality increased with increasing land use intensity. Simultaneously, the balance between herbivores and natural enemies turned increasingly towards herbivore dominance and natural enemy failure. Under natural conditions, there were more frequently significant effects of belowground herbivores and their natural enemies on plant performance, whereas there were more aboveground effects in agroecosystems. This result was partly due to the “boom-bust” behavior of the shoot herbivore population. Plant responses to herbivore or natural enemy removal were much more abrupt than the imposed smooth land use intensity gradient. This may be due to the presence of multiple trophic levels aboveground and belowground. Our model suggests that destabilization and extinction are more likely to occur in agroecosystems than in natural communities, but the shape of the relationship is nonlinear under the influence of multiple trophic interactions.

A Method of Drusen Measurement Based on the Geometry of Fundus Reflectance

BACKGROUND: The hallmarks of age-related macular degeneration, the leading cause of blindness in the developed world, are the subretinal deposits known as drusen. Drusen identification and measurement play a key role in clinical studies of this disease. Current manual methods of drusen measurement are laborious and subjective. Our purpose was to expedite clinical research with an accurate, reliable digital method. METHODS: An interactive semi-automated procedure was developed to level the macular background reflectance for the purpose of morphometric analysis of drusen. 12 color fundus photographs of patients with age-related macular degeneration and drusen were analyzed. After digitizing the photographs, the underlying background pattern in the green channel was leveled by an algorithm based on the elliptically concentric geometry of the reflectance in the normal macula: the gray scale values of all structures within defined elliptical boundaries were raised sequentially until a uniform background was obtained. Segmentation of drusen and area measurements in the central and middle subfields (1000 μm and 3000 μm diameters) were performed by uniform thresholds. Two observers using this interactive semi-automated software measured each image digitally. The mean digital measurements were compared to independent stereo fundus gradings by two expert graders (stereo Grader 1 estimated the drusen percentage in each of the 24 regions as falling into one of four standard broad ranges; stereo Grader 2 estimated drusen percentages in 1% to 5% intervals). RESULTS: The mean digital area measurements had a median standard deviation of 1.9%. The mean digital area measurements agreed with stereo Grader 1 in 22/24 cases. The 95% limits of agreement between the mean digital area measurements and the more precise stereo gradings of Grader 2 were -6.4 % to +6.8 % in the central subfield and -6.0 % to +4.5 % in the middle subfield. The mean absolute differences between the digital and stereo gradings 2 were 2.8 +/- 3.4% in the central subfield and 2.2 +/- 2.7% in the middle subfield. CONCLUSIONS: Semi-automated, supervised drusen measurements may be done reproducibly and accurately with adaptations of commercial software. This technique for macular image analysis has potential for use in clinical research

The distribution of burden of dental caries in schoolchildren: a critique of the high-risk caries prevention strategy for populations

BACKGROUND: The 'high-risk approach' is a commonly adopted strategy recommended for the prevention of dental caries in populations. The scientific basis for the strategy has been questioned. The objective of this study is to assess the contribution that children identified at 'high-risk' made towards the total of new caries lesions over a 4-year period, by analysing the distribution of new lesions per 100 children. METHODS: Data are from the National Preventive Dentistry Demonstration Programme (NPDDP) in the United States. The analyses identified the distribution of new carious lesions over a 4-year period in four groups of 7 year-old children who received differing preventive regimes. RESULTS: The majority of new lesions occurred in those children classified at lowest caries risk at baseline. Irrespective of the preventive regime adopted and the initial caries levels, children classified as 'highest risk' contributed less than 6% of the total number of new lesions developing over 4 years. CONCLUSION: These findings challenge the basis for the adoption of a high-risk strategy

The meaning and measurement of implementation climate

<p>Abstract</p> <p>Background</p> <p>Climate has a long history in organizational studies, but few theoretical models integrate the complex effects of climate during innovation implementation. In 1996, a theoretical model was proposed that organizations could develop a positive climate for implementation by making use of various policies and practices that promote organizational members' means, motives, and opportunities for innovation use. The model proposes that implementation climate--or the extent to which organizational members perceive that innovation use is expected, supported, and rewarded--is positively associated with implementation effectiveness. The implementation climate construct holds significant promise for advancing scientific knowledge about the organizational determinants of innovation implementation. However, the construct has not received sufficient scholarly attention, despite numerous citations in the scientific literature. In this article, we clarify the meaning of implementation climate, discuss several measurement issues, and propose guidelines for empirical study.</p> <p>Discussion</p> <p>Implementation climate differs from constructs such as organizational climate, culture, or context in two important respects: first, it has a strategic focus (implementation), and second, it is innovation-specific. Measuring implementation climate is challenging because the construct operates at the organizational level, but requires the collection of multi-dimensional perceptual data from many expected innovation users within an organization. In order to avoid problems with construct validity, assessments of within-group agreement of implementation climate measures must be carefully considered. Implementation climate implies a high degree of within-group agreement in climate perceptions. However, researchers might find it useful to distinguish implementation climate level (the average of implementation climate perceptions) from implementation climate strength (the variability of implementation climate perceptions). It is important to recognize that the implementation climate construct applies most readily to innovations that require collective, coordinated behavior change by many organizational members both for successful implementation and for realization of anticipated benefits. For innovations that do not possess these attributes, individual-level theories of behavior change could be more useful in explaining implementation effectiveness.</p> <p>Summary</p> <p>This construct has considerable value in implementation science, however, further debate and development is necessary to refine and distinguish the construct for empirical use.</p

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

[Plasma 2020 Decadal] Disentangling the Spatiotemporal Structure of Turbulence Using Multi-Spacecraft Data

This white paper submitted for 2020 Decadal Assessment of Plasma Science concerns the importance of multi-spacecraft missions to address fundamental questions concerning plasma turbulence. Plasma turbulence is ubiquitous in the universe, and it is responsible for the transport of mass, momentum, and energy in such diverse systems as the solar corona and wind, accretion discs, planet formation, and laboratory fusion devices. Turbulence is an inherently multi-scale and multi-process phenomenon, coupling the largest scales of a system to sub-electron scales via a cascade of energy, while simultaneously generating reconnecting current layers, shocks, and a myriad of instabilities and waves. The solar wind is humankind's best resource for studying the naturally occurring turbulent plasmas that permeate the universe. Since launching our first major scientific spacecraft mission, Explorer 1, in 1958, we have made significant progress characterizing solar wind turbulence. Yet, due to the severe limitations imposed by single point measurements, we are unable to characterize sufficiently the spatial and temporal properties of the solar wind, leaving many fundamental questions about plasma turbulence unanswered. Therefore, the time has now come wherein making significant additional progress to determine the dynamical nature of solar wind turbulence requires multi-spacecraft missions spanning a wide range of scales simultaneously. A dedicated multi-spacecraft mission concurrently covering a wide range of scales in the solar wind would not only allow us to directly determine the spatial and temporal structure of plasma turbulence, but it would also mitigate the limitations that current multi-spacecraft missions face, such as non-ideal orbits for observing solar wind turbulence. Some of the fundamentally important questions that can only be addressed by in situ multipoint measurements are discussed

The prevalence of obesity in children with autism: a secondary data analysis using nationally representative data from the National Survey of Children's Health

<p>Abstract</p> <p>Background</p> <p>The prevalence of childhood obesity has increased dramatically in the last two decades and numerous efforts to understand, intervene on, and prevent this significant threat to children's health are underway for many segments of the pediatric population. Understanding the prevalence of obesity in populations of children with developmental disorders is an important undertaking, as the factors that give rise to obesity may not be the same as for typically developing children, and because prevention and treatment efforts may need to be tailored to meet their needs and the needs of their families. The goal of the current study was to estimate the prevalence of obesity in children and adolescents with autism.</p> <p>Methods</p> <p>This study was a secondary data analysis of cross-sectional nationally representative data collected by telephone interview of parents/guardians on 85,272 children ages 3-17 from the 2003-2004 National Survey of Children's Health (NSCH). Autism was determined by response to the question, "Has a doctor or health professional ever told you that your child has autism?" Children and adolescents were classified as obese accordingto CDC guidelines for body mass index (BMI) for age and sex.</p> <p>Results</p> <p>The prevalence of obesity in children with autism was 30.4% compared to 23.6% of children without autism (p = .075). The unadjusted odds of obesity in children with autism was 1.42 (95% confidence interval (CI): 1.00, 2.02, p = .052) compared to children without autism.</p> <p>Conclusions</p> <p>Based on US nationally representative data, children with autism have a prevalence of obesity at least as high as children overall. These findings suggest that additional research is warranted to understand better the factors that influence the development of obesity in this population of children.</p

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721