Giant Cell Arteritis Presenting as Small Bowel Infarction

Giant cell arteritis predominantly affects cranial arteries and rarely involves other sites. We report a patient who presented with small bowel obstruction because of infarction from mesenteric giant cell arteritis. She had an unusual cause of her obstruction and a rare manifestation of giant cell arteritis. In spite of aggressive therapy with steroids, she died a month later because of multiple complications. We discuss the diagnosis and management of small bowel obstruction and differential diagnosis of vasculitis of the gastrointestinal tract. We were able to find 11 cases of bowel involvement with giant cell arteritis in the English literature. This case report illustrates that giant cell arteritis can be a cause of small bowel obstruction and bowel infarction. In the proper clinical setting, vasculitides need to be considered early in the differential diagnosis when therapy may be most effective

Design optimisation of an offshore vertical axis wind turbine

Horizontal axis wind turbines have a number of limitations for offshore operations, particularly in deep water (i.e. over 50 m). For example, scalability restrictions, the necessity for high lift installations offshore requiring specialist vessels, high gravitational and aerodynamic moments on the support structure and a need to maintain rotary equipment at heights typically over 60–80 m. Conversely, vertical axis wind turbines have several inherent attributes that offer some advantages for offshore operations, particularly their scalability and low over-turning moments with better accessibility to drivetrain components. This paper describes the aerodynamic optimisation of a novel 10 MW vertical axis wind turbine rotor shape offering a low-stress design to minimise manufacturing and maintenance costs of the whole turbine assembly including the supporting structure and foundations. The Aerogenerator vertical axis wind turbine is self-supporting so does not require a supporting tower, giving a low centre of gravity and producing significantly lower aerodynamic over-turning moments than conventional vertical axis wind turbines or horizontal axis wind turbines, making it a credible option for a floating, deep water platform. A numerical optimisation procedure is described to minimise the Aerogenerator weight while imposing aerodynamic, mechanical and structural side constraints. The study proposes a novel ‘sycamore’-shaped rotor design that demonstrates a lower cost of energy compared with conventional offshore turbines

Protection against Diarrhea Associated with Giardia intestinalis Is Lost with Multi-Nutrient Supplementation: A Study in Tanzanian Children

Giardia intestinalis is a well-known cause of diarrhea in industrialized countries. In children in developing countries, asymptomatic infections are common and their role as cause of diarrhea has been questioned. In a cohort of rural Tanzanian pre-school children, we assessed the association between the presence of Giardia at baseline and subsequent diarrhea risk. The study was conducted in the context of a randomised trial assessing the effect of supplementation with zinc and other micro-nutrients on malaria, and half of the children daily received a multi-nutrient supplement. Surprisingly, we found that the presence of Giardia at baseline was associated with a substantial reduction in diarrhea risk. Multivariate statistical analysis showed that this protection could not be explained by differences in age or walking distance to the dispensary between children with and without Giardia. Because we cannot exclude that children differed in other (unmeasured) characteristics, we cannot draw firm conclusions about the causality of the observed association, but our findings support the view that the parasite is not an important cause of diarrhea in highly endemic settings. Striking was that the Giardia-associated protection was lost when children received multi-nutrients. Our data do not provide information about the mechanisms involved, but suggest that multi-nutrients may influence the compositionor pathogenicity of intestinal biota

Susceptibility of Anopheles stephensi to Plasmodium gallinaceum: A Trait of the Mosquito, the Parasite, and the Environment

Vector susceptibility to Plasmodium infection is treated primarily as a vector trait, although it is a composite trait expressing the joint occurrence of the parasite and the vector with genetic contributions of both. A comprehensive approach to assess the specific contribution of genetic and environmental variation on "vector susceptibility" is lacking. Here we developed and implemented a simple scheme to assess the specific contributions of the vector, the parasite, and the environment to "vector susceptibility." To the best of our knowledge this is the first study that employs such an approach.We conducted selection experiments on the vector (while holding the parasite "constant") and on the parasite (while holding the vector "constant") to estimate the genetic contributions of the mosquito and the parasite to the susceptibility of Anopheles stephensi to Plasmodium gallinaceum. We separately estimated the realized heritability of (i) susceptibility to parasite infection by the mosquito vector and (ii) parasite compatibility (transmissibility) with the vector while controlling the other. The heritabilities of vector and the parasite were higher for the prevalence, i.e., fraction of infected mosquitoes, than the corresponding heritabilities of parasite load, i.e., the number of oocysts per mosquito.The vector's genetics (heritability) comprised 67% of "vector susceptibility" measured by the prevalence of mosquitoes infected with P. gallinaceum oocysts, whereas the specific contribution of parasite genetics (heritability) to this trait was only 5%. Our parasite source might possess minimal genetic diversity, which could explain its low heritability (and the high value of the vector). Notably, the environment contributed 28%. These estimates are relevant only to the particular system under study, but this experimental design could be useful for other parasite-host systems. The prospects and limitations of the genetic manipulation of vector populations to render the vector resistant to the parasite are better considered on the basis of this framework

Evolutionary Patterning: A Novel Approach to the Identification of Potential Drug Target Sites in Plasmodium falciparum

Malaria continues to be the most lethal protozoan disease of humans. Drug development programs exhibit a high attrition rate and parasite resistance to chemotherapeutic drugs exacerbates the problem. Strategies that limit the development of resistance and minimize host side-effects are therefore of major importance. In this study, a novel approach, termed evolutionary patterning (EP), was used to identify suitable drug target sites that would minimize the emergence of parasite resistance. EP uses the ratio of non-synonymous to synonymous substitutions (ω) to assess the patterns of evolutionary change at individual codons in a gene and to identify codons under the most intense purifying selection (ω≤0.1). The extreme evolutionary pressure to maintain these residues implies that resistance mutations are highly unlikely to develop, which makes them attractive chemotherapeutic targets. Method validation included a demonstration that none of the residues providing pyrimethamine resistance in the Plasmodium falciparum dihydrofolate reductase enzyme were under extreme purifying selection. To illustrate the EP approach, the putative P. falciparum glycerol kinase (PfGK) was used as an example. The gene was cloned and the recombinant protein was active in vitro, verifying the database annotation. Parasite and human GK gene sequences were analyzed separately as part of protozoan and metazoan clades, respectively, and key differences in the evolutionary patterns of the two molecules were identified. Potential drug target sites containing residues under extreme evolutionary constraints were selected. Structural modeling was used to evaluate the functional importance and drug accessibility of these sites, which narrowed down the number of candidates. The strategy of evolutionary patterning and refinement with structural modeling addresses the problem of targeting sites to minimize the development of drug resistance. This represents a significant advance for drug discovery programs in malaria and other infectious diseases

Degrees of change: between and within population variation in thermal reaction norms of phenology in a viviparous lizard

As the earth warms, populations will be faced with novel environments to which they may not be adapted. In the short term, populations can be buffered against the negative effects, or maximize the beneficial effects, of such environmental change via phenotypic plasticity and, in the longer term, via adaptive evolution. However, the extent and direction of these population-level responses will be dependent on the degree to which responses vary among the individuals within them (i.e., within population variation in plasticity), which is, itself, likely to vary among populations. Despite this, we have estimates of among-individual variation in plastic responses across multiple populations for only a few systems. This lack of data limits our ability to predict the consequences of environmental change for population and species persistence accurately. Here, we utilized a 16-yr data set from climatically distinct populations of the viviparous skink Niveoscincus ocellatus tracking over 1,200 litters from more than 600 females from each population to examine inter- and intrapopulation variability in the response of parturition date to environmental temperature. We found that these populations share a common population-mean reaction norm but differ in the degree to which reaction norms vary among individuals. These results suggest that even where populations share a common mean-level response, we cannot assume that they will be affected similarly by altered environmental conditions. If we are to assess how changing climates will impact species and populations accurately, we require estimates of how plastic responses vary both among and within populations

Electroanatomic mapping of right atrial activation in patients with and without paroxysmal atrial fibrillation

Inter-atrial conduction delay in patients with atrial fibrillation (AF) has been reported. However, the area of this conduction delay has not been well identified. The activation time and conduction velocity over the right atrial endocardium were evaluated during sinus rhythm using the CARTO mapping technique in 6 patients with paroxysmal AF (AF group) and 11 patients without history of AF (control group). No significant differences were observed between the 2 groups in the mean activation times and conduction velocities from the earliest activation site to the superior septum. His bundle area and coronary sinus ostium, or in the total activation times of the right atrium. There was no significant difference between the two groups in the local conduction velocity between 2 adjacent sites in the free wall, septum and bottom of the right atrium. This study suggests the previously reported conduction delay in the posteroseptal region in patients with paroxysmal AF might locate within the posterior inter-atrial septum