Spatial Access to Emergency Services in Low- and Middle-Income Countries: A GIS-Based Analysis

Injury is a leading cause of the global disease burden, accounting for 10 percent of all deaths worldwide. Despite 90 percent of these deaths occurring in low and middle-income countries (LMICs), the majority of trauma research and infrastructure development has taken place in high-income settings. Furthermore, although accessible services are of central importance to a mature trauma system, there remains a paucity of literature describing the spatial accessibility of emergency services in LMICs. Using data from the Service Provision Assessment component of the Demographic and Health Surveys of Namibia and Haiti we defined the capabilities of healthcare facilities in each country in terms of their preparedness to provide emergency services. A Geographic Information System-based network analysis method was used to define 5- 10- and 50-kilometer catchment areas for all facilities capable of providing 24-hour care, higher-level resuscitative services or tertiary care. The proportion of a country’s population with access to each level of service was obtained by amalgamating the catchment areas with a population layer. A significant proportion of the population of both countries had poor spatial access to lower level services with 25% of the population of Haiti and 51% of the population of Namibia living further than 50 kilometers from a facility capable of providing 24-hour care. Spatial access to tertiary care was considerably lower with 51% of Haitians and 72% of Namibians having no access to these higher-level services within 50 kilometers. These results demonstrate a significant disparity in potential spatial access to emergency services in two LMICs compared to analogous estimates from high-income settings, and suggest that strengthening the capabilities of existing facilities may improve the equity of emergency services in these countries. Routine collection of georeferenced patient and facility data in LMICs will be important to understanding how spatial access to services influences outcomes.     

A comparison of the structure,composition and mechanical properties of anosteocytic vertebrae of medaka (O. latipes) and osteocytic vertebrae of zebrafish (D. rerio)

Medaka (O. latipes) and zebrafish (D. rerio) are two teleost fish increasingly used as models to study human skeletal diseases. Although they are similar in size, swimming pattern and many other characteristics, these two species are very distant from an evolutionary point of view (by at least 100 million years). A prominent difference between the skeletons of medaka and zebrafish is the total absence of osteocytes in medaka (anosteocytic), while zebrafish bone contains numerous osteocytes (osteocytic). This fundamental difference suggests the possibility that the bony elements of their skeleton may be different in a variety of other aspects, structural, mechanical or both, particularly in heavily loaded bones like the vertebrae. Here we report on the results of a comparative study that aimed to determine the similarities and differences in medaka and zebrafish vertebrae in terms of their macro- to nanostructure, composition and mechanical properties. Our results reveal many similarities between medaka and zebrafish vertebrae, making the lack or presence of osteocytes the only major difference between the bones of these two species.     

The effect of steepness of temporal resource gradients on spatial root allocation

Plants are able to discriminately allocate greater biomass to organs that grow under higher resource levels. Recent evidence demonstrates that split-root plants also discriminately allocate more resources to roots that grow under dynamically improving nutrient levels, even when their other roots grow in richer patches. Here, we further tested whether, besides their responsiveness to the direction of resource gradients, plants are also sensitive to the steepness of environmental trajectories. Split-root Pisum sativum plants were grown so that one of their roots developed under constantly-high nutrient levels and the other root was subjected to dynamically improving nutrient levels of variable steepness. As expected, plants usually allocated a greater proportion of their biomass to roots that developed under constantly high resource availability; however, when given a choice, they allocated greater biomass to roots that initially experienced relatively low but steeply improving nutrient availabilities than to roots that developed under continuously-high nutrient availability. Such discrimination was not observed when the roots in the poor patch experienced only gentler improvements in nutrient availability. The results are compatible with the notion that responsiveness to the direction and steepness of environmental gradients could assist annual plants to increase their performance by anticipating resource availabilities foreseeable before the end of the growing season. The results exemplify the ability of plants to integrate and utilize environmental information and execute adaptive behaviors which, until recently, were attributed only to animals with central nervous systems.Key words: anticipatory responses, environmental information, foraging, gradient perception, phenotypic plasticity, plant behavior, rate of change, resource gradients     

Transition of endothelium to cartilage and bone

Mesenchymal stromal cells (MSCs) are capable of differentiating into bone-forming osteoblasts. A recent Nature Medicine study (Medici et al., 2010) shows that the mislocalized bone in the human disease fibrodisplasia ossificans progressiva (FOP) originates from vascular endothelium that gives rise to MSCs.     

The Expression of the Beta Cell-Derived Autoimmune Ligand for the Killer Receptor Nkp46 Is Attenuated in Type 2 Diabetes

NK cells rapidly kill tumor cells, virus infected cells and even self cells. This is mediated via killer receptors, among which NKp46 (NCR1 in mice) is prominent. We have recently demonstrated that in type 1 diabetes (T1D) NK cells accumulate in the diseased pancreas and that they manifest a hyporesponsive phenotype. In addition, we found that NKp46 recognizes an unknown ligand expressed by beta cells derived from humans and mice and that blocking of NKp46 activity prevented diabetes development. Here we investigated the properties of the unknown NKp46 ligand. We show that the NKp46 ligand is mainly located in insulin granules and that it is constitutively secreted. Following glucose stimulation the NKp46 ligand translocates to the cell membrane and its secretion decreases. We further demonstrate by using several modalities that the unknown NKp46 ligand is not insulin. Finally, we studied the expression of the NKp46 ligand in type 2 diabetes (T2D) using 3 different in vivo models and 2 species; mice and gerbils. We demonstrate that the expression of the NKp46 ligand is decreased in all models of T2D studied, suggesting that NKp46 is not involved in T2D.     

YopP-Expressing Variant of Y. pestis Activates a Potent Innate Immune Response Affording Cross-Protection against Yersiniosis and Tularemia

Plague, initiated by Yersinia pestis infection, is a rapidly progressing disease with a high mortality rate if not quickly treated. The existence of antibiotic-resistant Y. pestis strains emphasizes the need for the development of novel countermeasures against plague. We previously reported the generation of a recombinant Y. pestis strain (Kim53ΔJ+P) that over-expresses Y. enterocolitica YopP. When this strain was administered subcutaneously to mice, it elicited a fast and effective protective immune response in models of bubonic, pneumonic and septicemic plague. In the present study, we further characterized the immune response induced by the Kim53ΔJ+P recombinant strain. Using a panel of mouse strains defective in specific immune functions, we observed the induction of a prompt protective innate immune response that was interferon-γ dependent. Moreover, inoculation of mice with Y. pestis Kim53ΔJ+P elicited a rapid protective response against secondary infection by other bacterial pathogens, including the enteropathogen Y. enterocolitica and the respiratory pathogen Francisella tularensis. Thus, the development of new therapies to enhance the innate immune response may provide an initial critical delay in disease progression following the exposure to highly virulent bacterial pathogens, extending the time window for successful treatment.     

Hexokinase mediates stomatal closure

Stomata, composed of two guard cells, are the gates whose controlled movement allows the plant to balance the demand for CO₂ for photosynthesis with the loss of water through transpiration. Increased guard‐cell osmolarity leads to the opening of the stomata and decreased osmolarity causes the stomata to close. The role of sugars in the regulation of stomata is not yet clear. In this study, we examined the role of hexokinase (HXK), a sugar‐phosphorylating enzyme involved in sugar‐sensing, in guard cells and its effect on stomatal aperture. We show here that increased expression of HXK in guard cells accelerates stomatal closure. We further show that this closure is induced by sugar and is mediated by abscisic acid. These findings support the existence of a feedback‐inhibition mechanism that is mediated by a product of photosynthesis, namely sucrose. When the rate of sucrose production exceeds the rate at which sucrose is loaded into the phloem, the surplus sucrose is carried toward the stomata by the transpiration stream and stimulates stomatal closure via HXK, thereby preventing the loss of precious water.     

Achieving 80% ten-fold cross-validated accuracy for secondary structure prediction by large-scale training

An integrated system of neural networks, called SPINE, is established and optimized for predicting structural properties of proteins. SPINE is applied to three-state secondary-structure and residue-solvent-accessibility (RSA) prediction in this paper. The integrated neural networks are carefully trained with a large dataset of 2640 chains, sequence profiles generated from multiple sequence alignment, representative amino acid properties, a slow learning rate, overfitting protection, and an optimized sliding-widow size. More than 200,000 weights in SPINE are optimized by maximizing the accuracy measured by Q(3) (the percentage of correctly classified residues). SPINE yields a 10-fold cross-validated accuracy of 79.5% (80.0% for chains of length between 50 and 300) in secondary-structure prediction after one-month (CPU time) training on 22 processors. An accuracy of 87.5% is achieved for exposed residues (RSA >95%). The latter approaches the theoretical upper limit of 88-90% accuracy in assigning secondary structures. An accuracy of 73% for three-state solvent-accessibility prediction (25%/75% cutoff) and 79.3% for two-state prediction (25% cutoff) is also obtained.     

Novel pyrazolopiperazinone- and pyrrolopiperazinone-based MCH-R1 antagonists

The synthesis and biological testing of novel classes of potent melanin-concentrating hormone (MCH-R1) antagonists based on pyrazolopiperazinone and pyrrolopiperazinone scaffolds are described.