Association of the ENPP1 rs997509 polymorphism with obesity in South African mixed ancestry learners

Background: The Ectonucleotide Pyrophosphatase Phosphodiesterase1 (ENPP1) polymorphisms have been associated with metabolic traits. There is no data on the effect of ENPP1 in South African children or adults. Objective: To investigate the role of K121Q (rs1044498), rs997509 and rs9402349 in obesity and other components of the metabolic syndrome. Design: A case-control study. Subjects: Sixty four obese and 64 lean mixed ancestry learners. Setting: Western Cape, South Africa. Main outcome measure: The EN PP1 rs997509T allele is independently associated with obesity in children of mixed ancestry from South Africa. Results: The T allele frequency of the rs997509 differed significantly between obese and controls, p=0.0100 and increased the risk of being obese, p = 0.0238. Furthermore, the estimated effect of the T allele was an increase of 8.6 cm in waist circumference, 10.2 kg in weight and a corresponding 4.9 kg/m2 in BMI. Individuals carrying both the 121Q and the T allele of rs997509 were more associated with obesity (odds ratio = 3.85, 95% CI: 1.13 to 13.09) whilst those carrying the C allele of rs997509 in the presence of 121Q were likely to be lean with odds ratio of obesity 0.41 (95% CI: 0.19 to 0.87). Conclusion: Our findings suggest that ENPP1 polymorphisms may contribute to different metabolic characteristics, all of which are associated with insulin resistance in mixed ancestry children of South Africa. However, a larger study is required to confirm findings of this study.East African Medical Journal Vol. 87 No. 8 August 201

Shade alters savanna grass layer structure and function along a gradient of canopy cover

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordData availability statement: Data used for this study are available as supporting information.Aim: In savannas, a grass-dominated ground layer is key to ecosystem function via grass–fire feedbacks that maintain open ecosystems. With woody encroachment, tree density increases, thereby decreasing light in the ground layer and potentially altering ecosystem function. We investigated how light availability can filter individual grass species distributions and whether different functional traits are associated with response to a shade gradient in a landscape experiencing woody encroachment. Location: Savanna–forest mosaic in the Cerrado domain, southeastern Brazil. Methods: Along an encroachment gradient of increasing tree leaf area index (LAI) and shade, we determined how changing light availability alters grass diversity and ground layer structure relative to grass cover and grass functional traits (photosynthetic pathway, underground storage organs, bud protection and traits related to grass shape, size and leaf dimensions). Results: Increasing shade led to a decrease in grass cover and grass species richness, and also compositional and functional changes. We found that where tree LAI reached 1, grass cover was reduced by 50% and species richness by 30%. While C4 grass species abundances decreased with increasing shade, the opposite pattern was true for C3 grasses. There were only small differences in light preferences among C4 subtypes, with phosphoenolpyruvate carboxykinase (PCK) species tolerating slightly more shaded conditions. Persistence of some C4 species under more shaded conditions was possible, likely due to an ability to store starch reserves via underground storage organs. Conclusions: Woody encroachment changes diversity and structure of the grassy layer that is critical to the functioning of savanna ecosystems, highlighting the dependence of the diverse grass layer on open and sunny conditions. Our results suggest a threshold of tree cover close to LAI ≈ 1 as being critical to cerrado grassy layer conservation.National Science Foundation (NSF)São Paulo Research Foundation (FAPESP)National Council for Scientific and Technological DevelopmentCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Assessing the cost of global biodiversity and conservation knowledge

Knowledge products comprise assessments of authoritative information supported by stan-dards, governance, quality control, data, tools, and capacity building mechanisms. Considerable resources are dedicated to developing and maintaining knowledge productsfor biodiversity conservation, and they are widely used to inform policy and advise decisionmakers and practitioners. However, the financial cost of delivering this information is largelyundocumented. We evaluated the costs and funding sources for developing and maintain-ing four global biodiversity and conservation knowledge products: The IUCN Red List ofThreatened Species, the IUCN Red List of Ecosystems, Protected Planet, and the WorldDatabase of Key Biodiversity Areas. These are secondary data sets, built on primary datacollected by extensive networks of expert contributors worldwide. We estimate that US$160million (range: US$116–204 million), plus 293 person-years of volunteer time (range: 278–308 person-years) valued at US$14 million (range US$12–16 million), were invested inthese four knowledge products between 1979 and 2013. More than half of this financingwas provided through philanthropy, and nearly three-quarters was spent on personnelcosts. The estimated annual cost of maintaining data and platforms for three of these knowl-edge products (excluding the IUCN Red List of Ecosystems for which annual costs were notpossible to estimate for 2013) is US$6.5 million in total (range: US$6.2–6.7 million). We esti-mated that an additional US$114 million will be needed to reach pre-defined baselines ofdata coverage for all the four knowledge products, and that once achieved, annual mainte-nance costs will be approximately US$12 million. These costs are much lower than those tomaintain many other, similarly important, global knowledge products. Ensuring that biodi-versity and conservation knowledge products are sufficiently up to date, comprehensiveand accurate is fundamental to inform decision-making for biodiversity conservation andsustainable development. Thus, the development and implementation of plans for sustain-able long-term financing for them is critical

Effects of Grassland Management Practices on Ant Functional Groups in Central North America

Tallgrass prairies of central North America have experienced disturbances including fire and grazing for millennia. Little is known about the effects of these disturbances on prairie ants, even though ants are thought to play major roles in ecosystem maintenance. We implemented three management treatments on remnant and restored grassland tracts in the central U.S., and compared the effects of treatment on abundance of ant functional groups. Management treatments were: (1) patch-burn graze—rotational burning of three spatially distinct patches within a fenced tract, and growing-season cattle grazing; (2) graze-and-burn—burning entire tract every 3 years, and growing-season cattle grazing, and (3) burn-only—burning entire tract every 3 years, but no cattle grazing. Ant species were classified into one of four functional groups. Opportunist ants and the dominant ant species, Formica montana, were more abundant in burn-only tracts than tracts managed with either of the grazing treatments. Generalists were more abundant in graze-and-burn tracts than in burn-only tracts. Abundance of F. montana was negatively associated with pre-treatment time since fire, whereas generalist ant abundance was positively associated. F. montanawere more abundant in restored tracts than remnants, whereas the opposite was true for subdominants and opportunists. In summary, abundance of the dominant F. montana increased in response to intense disturbances that were followed by quick recovery of plant biomass. Generalist ant abundance decreased in response to those disturbances, which we attribute to the effects of competitive dominance of F. montana upon the generalists

Blooming Artifact Reduction in Coronary Artery Calcification by A New De-blooming Algorithm: Initial Study

The aim of this study was to investigate the use of de-blooming algorithm in coronary CT angiography (CCTA) for optimal evaluation of calcified plaques. Calcified plaques were simulated on a coronary vessel phantom and a cardiac motion phantom. Two convolution kernels, standard (STND) and high-definition standard (HD STND), were used for imaging reconstruction. A dedicated de-blooming algorithm was used for imaging processing. We found a smaller bias towards measurement of stenosis using the deblooming algorithm (STND: bias 24.6% vs 15.0%, range 10.2% to 39.0% vs 4.0% to 25.9%; HD STND: bias 17.9% vs 11.0%, range 8.9% to 30.6% vs 0.5% to 21.5%). With use of de-blooming algorithm, specificity for diagnosing significant stenosis increased from 45.8% to 75.0% (STND), from 62.5% to 83.3% (HD STND); while positive predictive value (PPV) increased from 69.8% to 83.3% (STND), from 76.9% to 88.2% (HD STND). In the patient group, reduction in calcification volume was 48.1 ± 10.3%, reduction in coronary diameter stenosis over calcified plaque was 52.4 ± 24.2%. Our results suggest that the novel de-blooming algorithm could effectively decrease the blooming artifacts caused by coronary calcified plaques, and consequently improve diagnostic accuracy of CCTA in assessing coronary stenosis

Kypho-IORT - a novel approach of intraoperative radiotherapy during kyphoplasty for vertebral metastases

<p>Abstract</p> <p>Background</p> <p>Instable and painful vertebral metastases in patients with progressive visceral metastases present a common therapeutic dilemma. We developed a novel approach to deliver intraoperative radiotherapy (IORT) during kyphoplasty and report the first treated case.</p> <p>Methods/Results</p> <p>60 year old patient with metastasizing breast cancer under chemotherapy presented with a newly diagnosed painful metastasis in the 12^ththoracic vertebra. Under general anaesthesia, a bipedicular approach into the vertebra was chosen with insertion of specially designed metallic sleeves to guide the electron drift tube of the miniature X-ray generator (INTRABEAM, Carl Zeiss Surgical, Oberkochen, Germany). This was inserted with a novel sheet designed for this approach protecting the drift tube. A radiation dose of 8 Gy in 5 mm distance (50 kV X-rays) was delivered. The kyphoplasty balloons (KyphX, Kyphon Inc, Sunnyvale) were inflated after IORT and polymethylmethacrylate cement was injected. The whole procedure lasted less than 90 minutes.</p> <p>Conclusion</p> <p>In conclusion, this novel, minimally invasive procedure can be performed in standard operating rooms and may become a valuable option for patients with vertebral metastases providing immediate stability and local control. A phase I/II study is under way to establish the optimal dose prescription.</p

Microcirculatory alterations: potential mechanisms and implications for therapy

Multiple experimental and human trials have shown that microcirculatory alterations are frequent in sepsis. In this review, we discuss the characteristics of these alterations, the various mechanisms potentially involved, and the implications for therapy. Sepsis-induced microvascular alterations are characterized by a decrease in capillary density with an increased number of stopped-flow and intermittent-flow capillaries, in close vicinity to well-perfused capillaries. Accordingly, the surface available for exchange is decreased but also is highly heterogeneous. Multiple mechanisms may contribute to these alterations, including endothelial dysfunction, impaired inter-cell communication, altered glycocalyx, adhesion and rolling of white blood cells and platelets, and altered red blood cell deformability. Given the heterogeneous nature of these alterations and the mechanisms potentially involved, classical hemodynamic interventions, such as fluids, red blood cell transfusions, vasopressors, and inotropic agents, have only a limited impact, and the microcirculatory changes often persist after resuscitation. Nevertheless, fluids seem to improve the microcirculation in the early phase of sepsis and dobutamine also can improve the microcirculation, although the magnitude of this effect varies considerably among patients. Finally, maintaining a sufficient perfusion pressure seems to positively influence the microcirculation; however, which mean arterial pressure levels should be targeted remains controversial. Some trials using vasodilating agents, especially nitroglycerin, showed promising initial results but they were challenged in other trials, so it is difficult to recommend the use of these agents in current practice. Other agents can markedly improve the microcirculation, including activated protein C and antithrombin, vitamin C, or steroids. In conclusion, microcirculatory alterations may play an important role in the development of sepsis-related organ dysfunction. At this stage, therapies to target microcirculation specifically are still being investigated

Involvement of mast cells in monocrotaline-induced pulmonary hypertension in rats

Background: Mast cells (MCs) are implicated in inflammation and tissue remodeling. Accumulation of lung MCs is described in pulmonary hypertension (PH); however, whether MC degranulation and c-kit, a tyrosine kinase receptor critically involved in MC biology, contribute to the pathogenesis and progression of PH has not been fully explored.Methods: Pulmonary MCs of idiopathic pulmonary arterial hypertension (IPAH) patients and monocrotaline-injected rats (MCT-rats) were examined by histochemistry and morphometry. Effects of the specific c-kit inhibitor PLX and MC stabilizer cromolyn sodium salt (CSS) were investigated in MCT-rats both by the preventive and therapeutic approaches. Hemodynamic and right ventricular hypertrophy measurements, pulmonary vascular morphometry and analysis of pulmonary MC localization/counts/activation were performed in animal model studies.Results: There was a prevalence of pulmonary MCs in IPAH patients and MCT-rats as compared to the donors and healthy rats, respectively. Notably, the perivascular MCs were increased and a majority of them were degranulated in lungs of IPAH patients and MCT-rats (p < 0.05 versus donor and control, respectively). In MCT-rats, the pharmacological inhibitions of MC degranulation and c-kit with CSS and PLX, respectively by a preventive approach (treatment from day 1 to 21 of MCT-injection) significantly attenuated right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH). Moreover, vascular remodeling, as evident from the significantly decreased muscularization and medial wall thickness of distal pulmonary vessels, was improved. However, treatments with CSS and PLX by a therapeutic approach (from day 21 to 35 of MCT-injection) neither improved hemodynamics and RVH nor vascular remodeling.Conclusions: The accumulation and activation of perivascular MCs in the lungs are the histopathological features present in clinical (IPAH patients) and experimental (MCT-rats) PH. Moreover, the accumulation and activation of MCs in the lungs contribute to the development of PH in MCT-rats. Our findings reveal an important pathophysiological insight into the role of MCs in the pathogenesis of PH in MCT- rats

Large Scale Application of Neural Network Based Semantic Role Labeling for Automated Relation Extraction from Biomedical Texts

To reduce the increasing amount of time spent on literature search in the life sciences, several methods for automated knowledge extraction have been developed. Co-occurrence based approaches can deal with large text corpora like MEDLINE in an acceptable time but are not able to extract any specific type of semantic relation. Semantic relation extraction methods based on syntax trees, on the other hand, are computationally expensive and the interpretation of the generated trees is difficult. Several natural language processing (NLP) approaches for the biomedical domain exist focusing specifically on the detection of a limited set of relation types. For systems biology, generic approaches for the detection of a multitude of relation types which in addition are able to process large text corpora are needed but the number of systems meeting both requirements is very limited. We introduce the use of SENNA (“Semantic Extraction using a Neural Network Architecture”), a fast and accurate neural network based Semantic Role Labeling (SRL) program, for the large scale extraction of semantic relations from the biomedical literature. A comparison of processing times of SENNA and other SRL systems or syntactical parsers used in the biomedical domain revealed that SENNA is the fastest Proposition Bank (PropBank) conforming SRL program currently available. 89 million biomedical sentences were tagged with SENNA on a 100 node cluster within three days. The accuracy of the presented relation extraction approach was evaluated on two test sets of annotated sentences resulting in precision/recall values of 0.71/0.43. We show that the accuracy as well as processing speed of the proposed semantic relation extraction approach is sufficient for its large scale application on biomedical text. The proposed approach is highly generalizable regarding the supported relation types and appears to be especially suited for general-purpose, broad-scale text mining systems. The presented approach bridges the gap between fast, cooccurrence-based approaches lacking semantic relations and highly specialized and computationally demanding NLP approaches