Polymeric IgA and immune complex concentrations in IgA-related renal disease

Polymeric IgA and immune complex concentrations in IgA-related renal disease. Polymeric IgA (PIgA) and immune complex concentrations in IgA-related renal disease were measured in cross sectional and longitudinal studies to establish the relationship between these parameters and both mucosal infection and renal dysfunction. These studies were performed in 50 patients with IgA nephropathy (IgAN), 17 patients with Henoch Schönlein purpura nephritis (HSPN), 11 control patients with IgA negative, diffuse mesangial proliferative glomerulonephritis (DMPGN) and 50 healthy controls. Total PIgA (PIgAT) and PIgA subclass concentrations were measured using a secretory component binding enzyme immunoassay and isotype specific immune complex concentrations were measured using conglutinin (K) binding immunoassays. In cross sectional studies patients with IgAN were found to have increased concentrations of PIgAT, PIgA1, K-IgA1 and K-IgA2 compared to controls. In the longitudinal studies controls and patients had significant increases in PIgAT and PIgA1 concentrations during infection. However, in patients with IgAN, the increases were greater, persisted for longer, and PIgA2 concentrations were also increased. K-IgA1 and K-IgA2 concentrations increased significantly during episodes of infection in IgAN patients in contrast to controls. Patients with HSPN had results similar to those of IgAN patients. No significant correlation was found between PIgA or K-IgA concentrations, and either serum creatinine concentrations or the degree of hematuria. The results indicate that patients with IgA-related renal disease have abnormal regulation of PIgA and immune complexed IgA, and that these abnormalities are exaggerated during mucosal infection

Effects of nebulised magnesium sulphate on inflammation and function of the guinea-pig airway

Magnesium sulphate is a potential treatment for acute severe asthma. However, the mechanisms and dose-response relationships are poorly understood. The first objective of this study was to examine whether inhaled magnesium sulphate exerts bronchodilator activity measured as bronchoprotection against histamine-induced bronchoconstriction in conscious guinea-pigs alone and combined with salbutamol. Secondly, we examined whether inhaled magnesium sulphate inhibits airways inflammation and function in models of neutrophilic and eosinophilic lung inflammation induced, respectively, by inhaled lipopolysaccharide or the inhaled antigen, ovalbumin (OVA). Airway function was measured in conscious guinea-pigs as specific airway conductance (sGaw) by whole-body plethysmography. Anti-inflammatory activity was measured against lung inflammatory cell influx induced by OVA inhalation in OVA-sensitised animals or by lipopolysaccharide (LPS) exposure of non-sensitised animals. Airway function (sGaw) was measured over 24 h after OVA exposure. Airway hyperresponsiveness to inhaled histamine and inflammatory cells in bronchoalveolar lavage fluid were recorded 24 h after OVA or LPS challenge. Histamine-induced bronchoconstriction was inhibited by inhaled magnesium sulphate or salbutamol alone and in combination, they produced synergistic bronchoprotection. LPS-induced neutrophil influx was inhibited by 6 days pretreatment with magnesium sulphate. Early and late asthmatic responses in OVA sensitised and challenged animals were attenuated by magnesium sulphate. Lung inflammatory cells were increased by OVA, macrophages being significantly reduced by magnesium sulphate. Nebulised magnesium sulphate protects against histamine-induced bronchoconstriction in conscious guinea-pigs and exerts anti-inflammatory activity against pulmonary inflammation induced by allergen (OVA) or LPS. These properties of magnesium sulphate explain its beneficial actions in acute asthma

Treaty doc.

This treaty governs mechanisms designed to ensure long-term conservation and sustainable use of certain species of fish, including tuna, swordfish, and marlin

A survey of facilitators and barriers to recruitment to the MAGNETIC trial

Background Recruitment to randomised controlled trials with children is challenging. It is imperative to understand the factors that boost or hinder recruitment of children to clinical trials. We conducted a survey of facilitators and barriers to recruitment to the MAGNETIC trial, using a previously developed web-based tool. Methods MAGNETIC is a multicentre randomised trial of nebulised magnesium in acute severe asthma, recruiting 508 children from 30 UK sites. Recruiters were asked to grade a list of factors from –3 to +3 depending on whether the factor was perceived as a strong, intermediate or weak barrier (–3 to –1) or facilitator (+1 to + 3), and using (0) if it was thought to be not applicable. Free text responses were invited on strategies applied to counter the identified barriers. Results The commonly identified facilitators were motivation and experience of study teams, effective communication and coordination between teams at site and between sites and the Clinical Trials Unit, the presence of designated research nurses, good trial management, clinical trial publicity, simple inclusion criteria, effective communication with parents and presentation of trial information in a simple and clear manner. The commonly identified barriers were heavy clinical workload, shift patterns of work, Good Clinical Practice (GCP) training, inadequate number of trained staff, time and setting of consent seeking, non-availability of research staff out of hours and parents' concerns about their child taking an experimental medicine. Having a designated research nurse, arranging GCP training and trial-related training sessions for staff were the most commonly reported interventions. Conclusions This study highlights important generic and trial-specific facilitators and barriers to recruitment to a paediatric trial in the acute setting and provides information on the recruitment strategies or interventions that were applied to overcome these barriers. This information can be very useful in informing the design and conduct of future clinical trials with children, particularly in the acute or emergency setting

MULTI-TEMPORAL AND MULTI-PLATFORM AGRICULTURAL LAND COVER CLASSIFICATION IN SOUTHEASTERN MICHIGAN

ABSTRACT We investigated the capabilities of multi-temporal and multi-platform remotely sensed imagery to differentiate crop types in the 14,600 ha Upper Tiffin watershed in southeastern Michigan, a primarily agricultural area. We focused on extracting signatures for corn, soybeans, wheat, alfalfa, and grasses as the major crops for the area. Input data included Landsat 5 TM, Terra/MODIS, and ASTER imagery for different parts of the 2004 and 2005 agricultural growing season. MODIS was selected to address the problems with obtaining sufficient repeat coverage of Landsat data during the growing season. We used both pixel-based and object-oriented classification techniques to assess the value of different techniques in leading to more useful agricultural land cover classifications. To contrast with these classification techniques, we predicted crop distributions using MODIS NDVI time-series profiles. ASTER data were investigated to see if its additional high-resolution bands and its multi-angle instruments could provide supplementary classification information. State and Federal agencies are active in the Upper Tiffin study area because of known problems with sediment and nutrient loading in local waterways. The Natural Resource Conservation Service (NRCS), part of the United States Department of Agriculture, used the results to understand how different land uses were affecting local water quality, and how the problems could be addressed

Observation of Bose-Einstein Condensation in a Strong Synthetic Magnetic Field

Extensions of Berry's phase and the quantum Hall effect have led to the discovery of new states of matter with topological properties. Traditionally, this has been achieved using gauge fields created by magnetic fields or spin orbit interactions which couple only to charged particles. For neutral ultracold atoms, synthetic magnetic fields have been created which are strong enough to realize the Harper-Hofstadter model. Despite many proposals and major experimental efforts, so far it has not been possible to prepare the ground state of this system. Here we report the observation of Bose-Einstein condensation for the Harper-Hofstadter Hamiltonian with one-half flux quantum per lattice unit cell. The diffraction pattern of the superfluid state directly shows the momentum distribution on the wavefuction, which is gauge-dependent. It reveals both the reduced symmetry of the vector potential and the twofold degeneracy of the ground state. We explore an adiabatic many-body state preparation protocol via the Mott insulating phase and observe the superfluid ground state in a three-dimensional lattice with strong interactions.Comment: 6 pages, 5 figures. Supplement: 6 pages, 4 figure

Comment on "The extent of forest in dryland biomes"

Bastin et al (Reports, 12 May 2017, p. 635) infer forest as more globally extensive than previously estimated using tree cover data. However, their forest definition does not reflect ecosystem function or biotic composition. These structural and climatic definitions inflate forest estimates across the tropics and undermine conservation goals, leading to inappropriate management policies and practices in tropical grassy ecosystems

Development of paediatric quality of inpatient care indicators for low-income countries - A Delphi study

BACKGROUND: Indicators of quality of care for children in hospitals in low-income countries have been proposed, but information on their perceived validity and acceptability is lacking. METHODS: Potential indicators representing structural and process aspects of care for six common conditions were selected from existing, largely qualitative WHO assessment tools and guidelines. We employed the Delphi technique, which combines expert opinion and existing scientific information, to assess their perceived validity and acceptability. Panels of experts, one representing an international panel and one a national (Kenyan) panel, were asked to rate the indicators over 3 rounds and 2 rounds respectively according to a variety of attributes. RESULTS: Based on a pre-specified consensus criteria most of the indicators presented to the experts were accepted: 112/137(82%) and 94/133(71%) for the international and local panels respectively. For the other indicators there was no consensus; none were rejected. Most indicators were rated highly on link to outcomes, reliability, relevance, actionability and priority but rated more poorly on feasibility of data collection under routine conditions. There was moderate to substantial agreement between the two panels of experts. CONCLUSIONS: This Delphi study provided evidence for the perceived usefulness of most of a set of measures of quality of hospital care for children proposed for use in low-income countries. However, both international and local experts expressed concerns that data for many process-based indicators may not currently be available. The feasibility of widespread quality assessment and responsiveness of indicators to intervention should be examined as part of continued efforts to improve approaches to informative hospital quality assessment

TGFβ pathway limits dedifferentiation following WNT and MAPK pathway activation to suppress intestinal tumourigenesis

Recent studies have suggested increased plasticity of differentiated cells within the intestine to act both as intestinal stem cells (ISCs) and tumour-initiating cells. However, little is known of the processes that regulate this plasticity. Our previous work has shown that activating mutations of Kras or the NF-κB pathway can drive dedifferentiation of intestinal cells lacking Apc. To investigate this process further, we profiled both cells undergoing dedifferentiation in vitro and tumours generated from these cells in vivo by gene expression analysis. Remarkably, no clear differences were observed in the tumours; however, during dedifferentiation in vitro we found a marked upregulation of TGFβ signalling, a pathway commonly mutated in colorectal cancer (CRC). Genetic inactivation of TGFβ type 1 receptor (Tgfbr1/Alk5) enhanced the ability of KrasG12D/+ mutation to drive dedifferentiation and markedly accelerated tumourigenesis. Mechanistically this is associated with a marked activation of MAPK signalling. Tumourigenesis from differentiated compartments is potently inhibited by MEK inhibition. Taken together, we show that tumours arising in differentiated compartments will be exposed to different suppressive signals, for example, TGFβ and blockade of these makes tumourigenesis more efficient from this compartment