Moist convection and its upscale effects in simulations of the Indian monsoon with explicit and parametrised convection

In common with many global models, the Met Office Unified Model (MetUM) climate simulations show large errors in Indian summer monsoon rainfall, with a wet bias over the equatorial Indian Ocean, a dry bias over India, and with too weak low-level flow into India. The representation of moist convection is a dominant source of error in global models, where convection must be parametrised, with the errors growing quickly enough to affect both weather and climate simulations. Here we use the first multi- week continental-scale MetUM simulations over India, with grid-spacings that allow explicit convection, to examine how convective parametrisation contributes to model biases in the region. Some biases are improved in the convection-permitting simulations with more intense rainfall over India, a later peak in the diurnal cycle of convective rainfall over land, and a reduced positive rainfall bias over the Indian Ocean. The simulations suggest that the reduced rainfall over the Indian Ocean leads to an enhanced monsoon circulation and transport of moisture into India. Increases in latent heating associated with increased convection over land deepen the monsoon trough and enhance water vapour transport into the continent. In addition, delayed continental convection allows greater surface insolation and, along with the same rain falling in more intense bursts, generates a drier land surface. This increases land-sea temperature contrasts, and further enhances onshore flow. Changes in the low-level water vapour advection into India are dominated by these changes to the flow, rather than to the moisture content in the flow. The results demonstrate the need to improve the representations of convection over both land and oceans to improve simulations of the monsoon

The nuclear cofactor receptor interacting protein-140 (RIP140) regulates the expression of genes involved in A beta generation

The receptor interacting protein-140 (RIP140) is a cofactor for several nuclear receptors and has been involved in the regulation of metabolic and inflammatory genes. We hypothesize that RIP140 may also affect Aβ generation because it modulates the activity of transcription factors previously implicated in amyloid precursor protein (APP) processing, such as peroxisome proliferator-activated receptor-γ (PPARγ). We found that the levels of RIP140 are reduced in Alzheimer's disease (AD) postmortem brains compared with healthy controls. In addition, in situ hybridization experiments revealed that RIP140 expression is enriched in the same brain areas involved in AD pathology, such as cortex and hippocampus. Furthermore, we provide evidence using cell lines and genetically modified mice that RIP140 is able to modulate the transcription of certain genes involved in AD pathology, such as β-APP cleaving enzyme (BACE1) and GSK3. Consequently, we found that RIP140 overexpression reduced the generation of Aβ in a neuroblastoma cell line by decreasing the transcription of β-APP cleaving enzyme via a PPARγ–dependent mechanism. The results of this study therefore provide molecular insights into common signaling pathways linking metabolic disease with AD

Development of a tool to predict outcome of Autologous Chondrocyte Implantation

Objective. The study had 2 objectives: first, to evaluate the success of autologous chondrocyte implantation (ACI) in terms of incidence of surgical re-intervention, including arthroplasty, and investigate predictors of successful treatment outcome. The second objective was to derive a tool predicting a patient’s arthroplasty risk following ACI. Design. In this Level II, prognostic study, 170 ACI-treated patients (110 males [aged 36.8 ± 9.4 years]; 60 females [aged 38.1 ± 10.2 years]) completed a questionnaire about further surgery on their knee treated with ACI 10.9 ± 3.5 years previously. Factors commonly assessed preoperatively (age, gender, defect location and number, previous surgery at this site, and the preoperative Lysholm score) were used as independent factors in regression analyses. Results. At final follow-up (maximum of 19 years post-ACI), 40 patients (23.5%) had undergone surgical re-intervention following ACI. Twenty-six patients (15.3%) underwent arthroplasty, more commonly females (25%) than males (10%; P = 0.001). Cox regression analyses identified 4 factors associated with re-intervention: age at ACI, multiple operations before ACI, patellar defects, and lower pretreatment Lysholm scores (Nagelkerke’s R2 = 0.20). Six predictive items associated with risk of arthroplasty following ACI (Nagelkerke’s R2 = 0.34) were used to develop the Oswestry Risk of Knee Arthroplasty index with internal crossvalidation. Conclusion. In a single-center study, we have identified 6 factors (age, gender, location and number of defects, number of previous operations, and Lysholm score before ACI) that appear to influence the likelihood of ACI patients progressing to arthroplasty. We have used this information to propose a formula or “tool” that could aid treatment decisions and improve patient selection for ACI

FGF signalling through RAS/MAPK and PI3K pathways regulates cell movement and gene expression in the chicken primitive streak without affecting E-cadherin expression

<p>Abstract</p> <p>Background</p> <p>FGF signalling regulates numerous aspects of early embryo development. During gastrulation in amniotes, epiblast cells undergo an epithelial to mesenchymal transition (EMT) in the primitive streak to form the mesoderm and endoderm. In mice lacking FGFR1, epiblast cells in the primitive streak fail to downregulate E-cadherin and undergo EMT, and cell migration is inhibited. This study investigated how FGF signalling regulates cell movement and gene expression in the primitive streak of chicken embryos.</p> <p>Results</p> <p>We find that pharmacological inhibition of FGFR activity blocks migration of cells through the primitive streak of chicken embryos without apparent alterations in the level or intracellular localization of E-cadherin. E-cadherin protein is localized to the periphery of epiblast, primitive streak and some mesodermal cells. FGFR inhibition leads to downregulation of a large number of regulatory genes in the preingression epiblast adjacent to the primitive streak, the primitive streak and the newly formed mesoderm. This includes members of the FGF, NOTCH, EPH, PDGF, and canonical and non-canonical WNT pathways, negative modulators of these pathways, and a large number of transcriptional regulatory genes. <it>SNAI2 </it>expression in the primitive streak and mesoderm is not altered by FGFR inhibition, but is downregulated only in the preingression epiblast region with no significant effect on E-cadherin. Furthermore, over expression of SNAIL has no discernable effect on E-cadherin protein levels or localization in epiblast, primitive streak or mesodermal cells. FGFR activity modulates distinct downstream pathways including RAS/MAPK and PI3K/AKT. Pharmacological inhibition of MEK or AKT indicate that these downstream effectors control discrete and overlapping groups of genes during gastrulation. FGFR activity regulates components of several pathways known to be required for cell migration through the streak or in the mesoderm, including RHOA, the non-canonical WNT pathway, PDGF signalling and the cell adhesion protein N-cadherin.</p> <p>Conclusions</p> <p>In chicken embryos, FGF signalling regulates cell movement through the primitive streak by mechanisms that appear to be independent of changes in E-cadherin expression or protein localization. The positive and negative effects on large groups of genes by pharmacological inhibition of FGF signalling, including major signalling pathways and transcription factor families, indicates that the FGF pathway is a focal point of regulation during gastrulation in chicken.</p

Independent component analysis (ICA) applied to dynamic oxygen-enhanced MRI (OE-MRI) for robust functional lung imaging at 3 T.

PURPOSE: Dynamic lung oxygen-enhanced MRI (OE-MRI) is challenging due to the presence of confounding signals and poor signal-to-noise ratio, particularly at 3 T. We have created a robust pipeline utilizing independent component analysis (ICA) to automatically extract the oxygen-induced signal change from confounding factors to improve the accuracy and sensitivity of lung OE-MRI. METHODS: Dynamic OE-MRI was performed on healthy participants using a dual-echo multi-slice spoiled gradient echo sequence at 3 T and cyclical gas delivery. ICA was applied to each echo within a thoracic mask. The ICA component relating to the oxygen-enhancement signal was automatically identified using correlation analysis. The oxygen-enhancement component was reconstructed, and the percentage signal enhancement (PSE) was calculated. The lung PSE of current smokers was compared with nonsmokers; scan-rescan repeatability, ICA pipeline repeatability, and reproducibility between two vendors were assessed. RESULTS: ICA successfully extracted a consistent oxygen-enhancement component for all participants. Lung tissue and oxygenated blood displayed the opposite oxygen-induced signal enhancements. A significant difference in PSE was observed between the lungs of current smokers and nonsmokers. The scan-rescan repeatability and the ICA pipeline repeatability were good. CONCLUSION: The developed pipeline demonstrated sensitivity to the signal enhancements of the lung tissue and oxygenated blood at 3 T. The difference in lung PSE between current smokers and nonsmokers indicates a likely sensitivity to lung function alterations that may be seen in mild pathology, supporting future use of our methods in patient studies

Regional differences in the response of rainfall to convectively coupled Kelvin waves over tropical Africa

The representation of convection remains one of the most important sources of bias in global models and evaluation methods are needed that show that models provide the correct mean state and variability; both for the correct reasons. Here we develop a novel approach for evaluating rainfall variability due to CCKWs in this region. A phase cycle was defined for the CCKW cycle in OLR and used to composite rainfall anomalies. We characterize the observed (TRMM) rainfall response to CCKWs over tropical Africa in April and evaluate the performance of regional climate model (RCM) simulations: a parameterized convection simulation (P25) and the first pan-Africa convection permitting simulation (CP4). TRMM mean rainfall is enhanced and suppressed by CCKW activity and the occurrence of extreme rainfall and dry days is coupled with CCKW activity. Focusing on regional differences, we show for the first time that: there is a dipole between West Africa and the Gulf of Guinea involving onshore/offshore shifts in rainfall; and the transition to enhanced rainfall over west equatorial Africa occurs one phase before the transition over east equatorial Africa. The global model used to drive the RCMs simulated CCKWs with mean amplitudes of 75%-82% of observations. The RCMs simulated coherent responses to the CCKWs and captured the large-scale spatial patterns and phase relationships in rainfall although the simulated rainfall response is weaker than observations and there are regional biases which are bigger away from the equator. P25 produced a closer match to TRMM mean rainfall anomalies than CP4 although the response in dry days was more closely simulated by CP4

Does mass drug administration for the integrated treatment of neglected tropical diseases really work? Assessing evidence for the control of schistosomiasis and soil-transmitted helminths in Uganda

This paper was one of four papers commissioned to review the role of social sciences in NTD control by TDR, the Special Programme for Research and Training on Tropical Diseases, which is executed by WHO and co-sponsored by UNICEF, UNDP, the World Bank and WHO.This article has been made available through the Brunel Open Access Publishing Fund.Background: Less is known about mass drug administration [MDA] for neglected tropical diseases [NTDs] than is suggested by those so vigorously promoting expansion of the approach. This paper fills an important gap: it draws upon local level research to examine the roll out of treatment for two NTDs, schistosomiasis and soil-transmitted helminths, in Uganda. Methods: Ethnographic research was undertaken over a period of four years between 2005-2009 in north-west and south-east Uganda. In addition to participant observation, survey data recording self-reported take-up of drugs for schistosomiasis, soil-transmitted helminths and, where relevant, lymphatic filariasis and onchocerciasis was collected from a random sample of at least 10% of households at study locations. Data recording the take-up of drugs in Ministry of Health registers for NTDs were analysed in the light of these ethnographic and social survey data. Results: The comparative analysis of the take-up of drugs among adults revealed that although most long term residents have been offered treatment at least once since 2004, the actual take up of drugs for schistosomiasis and soil-transmitted helminths varies considerably from one district to another and often also within districts. The specific reasons why MDA succeeds in some locations and falters in others relates to local dynamics. Issues such as population movement across borders, changing food supply, relations between drug distributors and targeted groups, rumours and conspiracy theories about the 'real' purpose of treatment, subjective experiences of side effects from treatment, alternative understandings of affliction, responses to social control measures and historical experiences of public health control measures, can all make a huge difference. The paper highlights the need to adapt MDA to local circumstances. It also points to specific generalisable issues, notably with respect to health education, drug distribution and more effective use of existing public health legislation. Conclusion: While it has been an achievement to have offered free drugs to so many adults, current standard practices of monitoring, evaluation and delivery of MDA for NTDs are inconsistent and inadequate. Efforts to integrate programmes have exacerbated the difficulties. Improved assessment of what is really happening on the ground will be an essential step in achieving long-term overall reduction of the NTD burden for impoverished communities.This article is available through the Brunel Open Access Publishing Fund

Theoretical Models of Sunspot Structure and Dynamics

Recent progress in theoretical modeling of a sunspot is reviewed. The observed properties of umbral dots are well reproduced by realistic simulations of magnetoconvection in a vertical, monolithic magnetic field. To understand the penumbra, it is useful to distinguish between the inner penumbra, dominated by bright filaments containing slender dark cores, and the outer penumbra, made up of dark and bright filaments of comparable width with corresponding magnetic fields differing in inclination by some 30 degrees and strong Evershed flows in the dark filaments along nearly horizontal or downward-plunging magnetic fields. The role of magnetic flux pumping in submerging magnetic flux in the outer penumbra is examined through numerical experiments, and different geometric models of the penumbral magnetic field are discussed in the light of high-resolution observations. Recent, realistic numerical MHD simulations of an entire sunspot have succeeded in reproducing the salient features of the convective pattern in the umbra and the inner penumbra. The siphon-flow mechanism still provides the best explanation of the Evershed flow, particularly in the outer penumbra where it often consists of cool, supersonic downflows.Comment: To appear in "Magnetic Coupling between the Interior and the Atmosphere of the Sun", eds. S.S. Hasan and R.J. Rutten, Astrophysics and Space Science Proceedings, Springer-Verlag, Heidelberg, Berlin, 200

Arterial pressure: agreement between a brachial cuff-based device and radial tonometry

Objectives: Aortic (central) blood pressure (BP) differs from brachial BP and may be a superior predictor of cardiovascular events. However, its measurement is currently restricted to research settings, owing to a moderate level of operator dependency. We tested a new noninvasive device in a large UK cohort. The device estimates central BP using measurements obtained with an upper arm cuff inflated to suprasystolic pressure. We compared these estimates with those obtained using radial tonometry as well as with invasively acquired measurements of aortic BP in a limited number of individuals. Methods: Consecutive cuff-based and tonometry-based estimates of the pressure waveform and the central BP were obtained from 1107 individuals (70 ± 6 years). Short-term and long-term reproducibility studies were performed on 28 individuals. Simultaneous cuff-based and invasively measured pressure traces were acquired and compared in an additional six individuals (65 ± 20 years). Results: Central systolic BP, as estimated by the cuff-based device, was found to be highly reproducible (coefficient of variation 4 and 8% for short and long-term reproducibility, respectively) and was comparable to that estimated by tonometry (average difference 3 ± 6 mmHg, intraclass correlation coefficient = 0.91). The cuff-based pressure waveforms were similar to those acquired invasively (cross-correlation coefficient 0.93), and the difference in the estimated central systolic BP was −5 ± 8 mmHg (P = 0.2). Conclusion: Cuff-based devices show promise to simplify the measurement of central BP, whilst maintaining a similar fidelity to tonometry. This could lead to improved adoption of estimates of central BP in clinical practice