Structural features of human immunoglobulin G that determine isotype-specific differences in complement activation.

Although very similar in sequence, the four subclasses of human immunoglobulin G (IgG) differ markedly in their ability to activate complement. Glu318-Lys320-Lys322 has been identified as a key binding motif for the first component of complement, C1q, and is present in all isotypes of Ig capable of activating complement. This motif, however, is present in all subclasses of human IgG, including those that show little (IgG2) or even no (IgG4) complement activity. Using point mutants of chimeric antibodies, we have identified specific residues responsible for the differing ability of the IgG subclasses to fix complement. In particular, we show that Ser at position 331 in gamma 4 is critical for determining the inability of that isotype to bind C1q and activate complement. Additionally, we provide further evidence that levels of C1q binding do not necessarily correlate with levels of complement activity, and that C1q binding alone is not sufficient for complement activation

A Problem Solving Approach to Identifying Civil Engineering Infrastructure Projects

Civil engineering infrastructure projects are solutions to problems facing communities, societies or even an entire nation. Addressing societal needs and problems is a key element of infrastructure project success. However, recent evidence suggests that decision makers often invest in projects that do not address clearly defined problems. Therefore, this research aims to contribute towards improving the identification process of civil engineering infrastructure projects. A desk study involving mapping of a generic infrastructure project life cycle onto two problem solving process models was undertaken. It was found that if civil engineering infrastructure projects are viewed as solutions to problems, ideas of a problem solving process can be adapted and incorporated into the identification process of infrastructure projects. This led to the design of a novel two-stage identification process for civil engineering infrastructure projects. The process brings together developers and concerned stakeholders to: first agree on the problem to be addressed, and second generate solutions, assess them and then choose a preferred solution to be implemented. Identifying civil engineering infrastructure projects in this manner ensures that public funds are spent on projects that address societal problems, provide the greatest benefits to society, and that they are spent in the most efficient way

Creating realistic synthetic populations at varying spatial scales: A comparative critique of population synthesis techniques

There are several established methodologies for generating synthetic populations. These include deterministic reweighting, conditional probability (Monte Carlo simulation) and simulated annealing. However, each of these approaches is limited by, for example, the level of geography to which it can be applied, or number of characteristics of the real population that can be replicated. The research examines and critiques the performance of each of these methods over varying spatial scales. Results show that the most consistent and accurate populations generated over all the spatial scales are produced from the simulated annealing algorithm. The relative merits and limitations of each method are evaluated in the discussion

On the Wiener-Hopf solution of water-wave interaction with a submerged elastic or poroelastic plate.

A solution to the problem of water-wave scattering by a semi-infinite submerged thin elastic plate, which is either porous or non-porous, is presented using the Wiener-Hopf technique. The derivation of the Wiener-Hopf equation is rather different from that which is used traditionally in water-waves problems, and it leads to the required equations directly. It is also shown how the solution can be computed straightforwardly using Cauchy-type integrals, which avoids the need to find the roots of the highly non-trivial dispersion equations. We illustrate the method with some numerical computations, focusing on the evolution of an incident wave pulse which illustrates the existence of two transmitted waves in the submerged plate system. The effect of the porosity is studied, and it is shown to influence the shorter-wavelength pulse much more strongly than the longer-wavelength pulse

Effects of Brief Mindfulness-Based Interventions on Health-Related Outcomes: a Systematic Review

Objectives Traditional mindfulness-based interventions (MBIs) have been applied successfully across many populations. The time commitment for these programs is often a barrier, and while brief MBIs have become popular, the impact of these on health-related outcomes is unclear as they have not yet been reviewed. Methods A search of databases, including Medline, Embase, and PsycINFO, was conducted with qualitative and case studies being excluded. Findings were summarized using a narrative approach for all studies that met the inclusion criteria. Results With one exception, all 85 studies that were included were randomized controlled trials and were relatively robust methodologically. Seventy-nine reported significant positive effects on at least one health-related outcome and over a quarter targeted a clinical population. The majority of studies focused on psychological outcomes, such as anxiety and depression, as well as emotion regulation, stress, and cognitive outcomes. Conclusions Despite heterogeneity of outcomes across studies, there is evidence that brief MBIs can impact numerous health-related outcomes, after only one session and with interventions as brief as 5 min. These interventions have the potential to be the initial steps leading to sustainable and positive health outcomes

Comparison of 20nm silver nanoparticles synthesized with and without a gold core: Structure, dissolution in cell culture media, and biological impact on macrophages

Widespread use of silver nanoparticles raises questions of environmental and biological impact. Many synthesis approaches are used to produce pure silver and silver-shell gold-core particles optimized for specific applications. Since both nanoparticles and silver dissolved from the particles may impact the biological response, it is important to understand the physicochemical characteristics along with the biological impact of nanoparticles produced by different processes. The authors have examined the structure, dissolution, and impact of particle exposure to macrophage cells of two 20 nm silver particles synthesized in different ways, which have different internal structures. The structures were examined by electron microscopy and dissolution measured in Rosewell Park Memorial Institute media with 10% fetal bovine serum. Cytotoxicity and oxidative stress were used to measure biological impact on RAW 264.7 macrophage cells. The particles were polycrystalline, but 20 nm particles grown on gold seed particles had smaller crystallite size with many high-energy grain boundaries and defects, and an apparent higher solubility than 20 nm pure silver particles. Greater oxidative stress and cytotoxicity were observed for 20 nm particles containing the Au core than for 20 nm pure silver particles. A simple dissolution model described the time variation of particle size and dissolved silver for particle loadings larger than 9 μg/ml for the 24-h period characteristic of many in-vitro studies

Health system performance assessment in small countries: The case study of Latvia

Managing the complexity that characterizes health systems requires sophisticated performance assessment information to support the decision‐making processes of healthcare stakeholders at various levels. Accordingly, in the past few decades, many countries have designed and implemented health system performance assessment (HSPA) programmes. Literature and practice agree on the key features that performance measurement in health should have, namely, multidimensionality, evidence‐based data collection, systematic benchmarking of results, shared design, transparent disclosure, and timeliness. Nevertheless, the specific characteristics of different countries may pose challenges in the implementation of such programmes. In the case of small countries, many of these challenges are common and related to their inherent characteristics, eg, small populations, small volumes of activity for certain treatments, and lack of benchmarks. Through the development of the case study of Latvia, this paper aims at discussing the challenges and opportunities for assessing health system performance in a small country. As a result, for each of the performance measurement features identified by the literature, the authors discuss the issues emerging when adopting them in Latvia and set out the potential solutions that have been designed during the development of the case study

Assessment of best single sample for finding chlamydia in women with and without symptoms: a diagnostic test study

Objective: to compare vulvovaginal swabs with endocervical swabs as optimal diagnostic sample for detection of Chlamydia trachomatis infection. Design: a diagnostic test study. Setting: an urban sexual health centre. Participants: 3973 women aged ≥16 years requesting testing for sexually transmitted infections. Interventions: participants took a vulvovaginal swab before routine examination, and clinicians took an endocervical swab during examination. Main outcome measure: diagnosis of chlamydia infection with samples analysed using the Aptima Combo-2 assay; positive results confirmed with the Aptima CT assay. Results: of the 3973 participants, 410 (10.3%) were infected with C trachomatis. Infected women were significantly younger (22 v 25 years, P<0.0001) and more likely to have symptoms suggestive of a bacterial sexually transmitted infection (53% v 41%, odds ratio 1.63 (95% CI 1.30 to 2.04)), be a contact of someone with a sexually transmitted infection (25% v 5%, odds ratio 6.18 (4.61 to 8.30)), clinically diagnosed with cervicitis (17% v 4%, odds ratio 4.92 (3.50 to 6.91)), and have pelvic inflammatory disease (9% v 3%, odds ratio 2.85 (1.87 to 4.33)). When women co-infected with gonorrhoea were included in the analysis, there was an association with mixed ethnicity (10% v 7%, odds ratio 1.53 (1.07 to 2.17)); but when those with gonorrhoea were removed, women of white ethnicity were significantly more likely to have chlamydia (85% v 80%, odds ratio 1.40 (1.03 to 1.91)). On analysis of complete paired results, vulvovaginal swabs were significantly more sensitive than endocervical swabs (97% (95% CI 95% to 98%) v 88% (85% to 91%), P<0.00001); corresponding specificities were 99.9% and 100%. In women with symptoms suggestive of a bacterial sexually transmitted infection, vulvovaginal swabs were significantly more sensitive than endocervical swabs (97% (93% to 98%) v 88% (83% to 92%), P=0.0008), as they were in women without symptoms (97% (94% to 99%) v 89% (84% to 93%), P=0.002). Conclusions: vulvovaginal swabs are significantly better than endocervical swabs at detecting chlamydia in women with and without symptoms suggestive of sexually transmitted infections. In those with symptoms, using endocervical samples rather than vulvovaginal swabs would have missed 9% of infections, or 1 in every 11 cases of chlamydia