Fibrin independent proinflammatory effects of tissuefactor in experimental crescentic glomerulonephritis

Fibrin independent proinflammatory effects of tissue factor in experimental crescentic glomerulonephritis.BackgroundTissue factor initiated glomerular fibrin deposition is an important mediator of injury in crescentic glomerulonephritis. Recent data have suggested noncoagulant roles for tissue factor in inflammation.MethodsTo test the hypothesis that in addition to its effects in initiating coagulation, tissue factor has proinflammatory effects in glomerulonephritis, rabbits given crescentic anti-glomerular basement membrane (GBM) antibody–induced glomerulonephritis were defibrinogenated with ancrod. One group of defibrinogenated rabbits was also given anti-tissue factor antibodies. Comparisons were made between these groups, as well as a third group that was neither defibrinogenated with ancrod nor given anti-tissue factor antibodies.ResultsDefibrinogenation alone abolished glomerular fibrin deposition, reduced crescent formation, and limited renal impairment (ancrod-treated, serum creatinine 274 ± 37 μmol/L; untreated 415 ± 51 μmol/L; P < 0.01). Tissue factor inhibition in defibrinogenated rabbits resulted in further protection of renal function (creatinine 140 ± 19 μmol/L, P < 0.01) and reduced proteinuria (0.4 ± 0.2g/day, untreated 2.6 ± 0.4 g/day, P <0.01), which was significantly increased by defibrinogenation alone (ancrod-treated, 5.6 ± 1.2 g/day). Anti-tissue factor antibodies (but not defibrinogenation alone) attenuated glomerular T-cell and macrophage recruitment, and major histocompatibility complex (MHC) class II expression.ConclusionThese results demonstrate important proinflammatory effects of tissue factor in crescentic glomerulonephritis that are fibrin independent and provide in vivo evidence for tissue factor's proinflammatory effects on MHC class II expression and leukocyte accumulation

In-situ monitoring for CVD processes

Aiming towards process control of industrial high yield/high volume CVD reactors, the potential of optical sensors as a monitoring tool has been explored. The sensors selected are based on both Fourier transform infrared spectroscopy (FTIR) and tunable diode laser spectroscopy (NIR-DLS). The former has the advantage of wide spectral capability, and well established databases. NIR-DLS spectroscopy has potentially high sensitivity, laser spatial resolution, and the benefits of comparatively easier integration capabilities-including optical fibre compatibility. The proposed technical approach for process control is characterised by a 'chemistry based' feedback system with in-situ optical data as input information. The selected optical sensors continuously analyze the gas phase near the surface of the growing layer. The spectroscopic data has been correlated with process performance and layer properties which, in turn establish data basis for process control. The new process control approach is currently being verified on different industrialised CVD coaters. One of the selected applications deals with the deposition of SnO2 layers on glass based on the oxidation of (CH3)2SnCl2, which is used in high volume production for low-E glazing

Relationships Between Recovery and Relapse, and Default and Repeated Episodes of Default in the Management of Acute Malnutrition in Children in Humanitarian Emergencies: A systematic review protocol

This protocol outlines plans for conducting a mixed-methods systematic review on acute malnutrition in humanitarian crises. The review will investigate the relationship between recovery/cure and relapse, and between relapse and default and/or return defaults/episodes of default in the management of acute malnutrition in children under five in humanitarian emergencies. The review will also explore the contexts in which acute malnutrition management programmes were implemented, in order to identify and describe how context influences relapse and default and/or return default/episodes. This review is funded through the Humanitarian Evidence Programme, a UK Aid-funded partnership between Oxfam and Feinstein International Center (FIC) at the Friedman School of Nutrition at Tufts University. The Humanitarian Evidence Programme aims to synthesize evidence in the humanitarian sector and communicate the findings to stakeholders, with the ultimate goal of improving humanitarian policy and practice

Exploiting changes in the tumour microenvironment with sequential cytokine and matrix metalloprotease inhibitor treatment in a murine breast cancer model

The study of treatment-induced changes in the tumour microenvironment might lead to effective combinations of biological therapy. IL-12 induced tumour regression and cure of an experimental murine breast cancer, HTH-K, but only after long-term treatment that was associated with chronic toxicity. During IL-12 therapy, tumour levels of the matrix metalloprotease MMP-9 declined and its inhibitor TIMP-1 was strongly induced. We therefore administered alternate cycles of IL-12 and the MMP inhibitor Batimastat (BB94) to mice. Therapeutic efficacy was increased compared with short-term IL-12 therapy but without the chronic toxicity associated with long-term IL-12 treatment. Image analysis of treated tumours revealed that BB94 prevented regeneration of tumour and stromal compartments that normally occurred after short-term IL-12 therapy. © 2000 Cancer Research Campaign http://www.bjcancer.co

Interleukin-4 deficiency enhances Th1 responses and crescentic glomerulonephritis in mice

Interleukin-4 deficiency enhances Th1 responses and crescentic glomerulonephritis in mice. Evidence suggests that crescentic glomerulonephritis (GN) is due to T helper cell 1 (Th1) directed delayed-type hypersensitivity (DTH)-like injury. As endogenous interleukin (IL)-4, (the pivotal cytokine in Th2 responses) may attenuate Th1 responses in this disease, we compared the development of crescentic GN, induced by a planted antigen, in mice genetically deficient in IL-4 (IL-4−/−) with disease in normal mice (IL-4+/+). IL-4−/− mice developed more severe GN with increased renal impairment (CCr 35 ± 7 μl/min vs. 133 ± 14 μl/min, P < 0.002) and crescent formation (55.7 ± 8.4% vs. 4.9 ± 1.2%, P < 0.002). This was associated with increased glomerular fibrin deposition, glomerular CD4+ T cell infiltration and macrophage recruitment. Systemically, IL-4−/− mice showed an increased antigen specific Th1 response indicated by increased skin DTH, and increased IgG3 and IgG2b. Decreased IgG1 levels indicated a reduced Th2 response. These results demonstrate a protective role for endogenous IL-4 in crescentic GN. They show that IL-4 deficiency promotes crescentic glomerular injury and amplifies local and systemic Th1 responses. They support the hypothesis that crescent formation results from Th1 immune responses to antigens in the glomerulus

Implementation of healthy food environment policies to prevent nutrition-related non-communicable diseases in Ghana : national experts’ assessment of Government action

Nutrition-related non-communicable diseases (NR-NCDs) are a global health problem, increasingly recognised as driven by unhealthy food environments. Yet little is known about government action to implement food environment-relevant policies, particularly in low-and lower-middle income countries. This study assessed government action, implementation gaps, and priorities to improve the food environment in Ghana. Using the Healthy Food-Environment Policy Index (Food-EPI), a panel comprising government and independent experts (n = 19) rated government action to improve the healthiness of food environment in Ghana against international best practices and according to steps within a policy cycle. Forty-three good practice indicators of food environment policy and infrastructure support were used, with ratings informed by systematically collected evidence of action validated by government officials. Following the rating exercise, the expert panel proposed and prioritized actions for government implementation. Three-quarters of all good practice indicators were rated at ‘low’/‘very little’ implementation. Restricting the marketing of breast milk substitutes was the only indicator rated “very high”. Of ten policy actions prioritized for implementation, restricting unhealthy food marketing in children’s settings and in the media were ranked the highest priority. Providing sufficient funds for nationally-relevant research on nutrition and NCDs was the highest priority infrastructure-support action. Other priority infrastructure-support actions related to leadership, monitoring and evaluation. This study identified gaps in Ghana’s implementation of internationally-recommended policies to promote healthy food environments. National stakeholders recommended actions, which will require legislation and leadership. The findings provide a baseline for measuring government progress towards implementing effective policies to prevent NR-NCDs

Factors influencing dietary behaviours in urban food environments in Africa: a systematic mapping review

Objective: To identify factors influencing dietary behaviours in urban food environments in Africa and identify areas for future research. Design: We systematically reviewed published/grey literature (protocol CRD4201706893). Findings were compiled into a map using a socio-ecological model on four environmental levels: individual, social, physical and macro. Setting: Urban food environments in Africa. Participants: Studies involving adolescents and adults (11–70 years, male/female). Results: Thirty-nine studies were included (six adolescent, fifteen adolescent/adult combined and eighteen adult). Quantitative methods were most common (twenty-eight quantitative, nine qualitative and two mixed methods). Studies were from fifteen African countries. Seventy-seven factors influencing dietary behaviours were identified, with two-thirds at the individual level (45/77). Factors in the social (11/77), physical (12/77) and macro (9/77) environments were investigated less. Individual-level factors that specifically emerged for adolescents included self-esteem, body satisfaction, dieting, spoken language, school attendance, gender, body composition, pubertal development, BMI and fat mass. Studies involving adolescents investigated social environment-level factors more, for example, sharing food with friends. The physical food environment was more commonly explored in adults, for example, convenience/availability of food. Macro-level factors associated with dietary behaviours were food/drink advertising, religion and food prices. Factors associated with dietary behaviour were broadly similar for men and women. Conclusions: The dominance of studies exploring individual-level factors suggests a need for research to explore how social, physical and macro-level environments drive dietary behaviours of adolescents and adults in urban Africa. More studies are needed for adolescents and men, and studies widening the geographical scope to encompass all African countries

Trade-off between angular and spatial resolutions in in vivo fiber tractography

Tractography is becoming an increasingly popular method to reconstruct white matter connections in vivo. The diffusion MRI data that tractography is based on requires a high angular resolution to resolve crossing fibers whereas high spatial resolution is required to distinguish kissing from crossing fibers. However, scan time increases with increasing spatial and angular resolutions, which can become infeasible in clinical settings. Here we investigated the trade-off between spatial and angular resolutions to determine which of these factors is most worth investing scan time in. We created a unique diffusion MRI dataset with 1.0mm isotropic resolution and a high angular resolution (100 directions) using an advanced 3D diffusion-weighted multi-slab EPI acquisition. This dataset was reconstructed to create subsets of lower angular (75, 50, and 25 directions) and lower spatial (1.5, 2.0, and 2.5mm) resolution. Using all subsets, we investigated the effects of angular and spatial resolutions in three fiber bundles-the corticospinal tract, arcuate fasciculus and corpus callosum-by analyzing the volumetric bundle overlap and anatomical correspondence between tracts. Our results indicate that the subsets of 25 and 50 directions provided inferior tract reconstructions compared with the datasets with 75 and 100 directions. Datasets with spatial resolutions of 1.0, 1.5, and 2.0mm were comparable, while the lowest resolution (2.5mm) datasets had discernible inferior quality. In conclusion, we found that angular resolution appeared to be more influential than spatial resolution in improving tractography results. Spatial resolutions higher than 2.0mm only appear to benefit multi-fiber tractography methods if this is not at the cost of decreased angular resolution

Strike-slip influenced stratigraphic and structural development of the Foula Sandstone Group, Shetland: implications for offshore Devonian basin development on the northern UK continental shelf

The island of Foula, located 25 km SW of Shetland, preserves a gently folded, 1.6 km thick sequence of Middle Devonian sandstones spectacularly exposed in kilometre-long cliff sections >350 m high. These rocks unconformably overlie likely Precambrian-age amphibolite facies basement rocks that are intruded by sheeted granites. The onshore succession is similar in age to the nearby Lower Clair Group offshore to the west. New mapping, incorporating the use of drone imagery in the inaccessible cliff sections, uses down-plunge projections to show that growth folding and faulting on Foula were contemporaneous with sedimentation during basin filling. The large-scale structural geometry is consistent with the regional constrictional strain due to the sinistral transtension associated with movements along the Walls Boundary–Great Glen fault zone system during the Mid-Devonian. Detrital zircon provenance studies indicate that the Devonian sequences of Foula (and nearby Melby in western Shetland) show similarities with the Clair Group and Orkney successions. We suggest that NE–SW transtensional fold development contemporaneous with regional subsidence in the Devonian basins of Scotland may be more widespread than previously realized. Large, kilometre-scale folds previously interpreted to be related to Permo-Carboniferous inversion may therefore have initiated earlier in the basin evolution sequence than previously realized