Improving resolution in multidimensional NMR using random quadrature detection with compressed sensing reconstruction.

NMR spectroscopy is central to atomic resolution studies in biology and chemistry. Key to this approach are multidimensional experiments. Obtaining such experiments with sufficient resolution, however, is a slow process, in part since each time increment in every indirect dimension needs to be recorded twice, in quadrature. We introduce a modified compressed sensing (CS) algorithm enabling reconstruction of data acquired with random acquisition of quadrature components in gradient-selection NMR. We name this approach random quadrature detection (RQD). Gradient-selection experiments are essential to the success of modern NMR and with RQD, a 50 % reduction in the number of data points per indirect dimension is possible, by only acquiring one quadrature component per time point. Using our algorithm (CSRQD), high quality reconstructions are achieved. RQD is modular and combined with non-uniform sampling we show that this provides increased flexibility in designing sampling schedules leading to improved resolution with increasing benefits as dimensionality of experiments increases, with particular advantages for 4- and higher dimensional experiments.Part of this work was performed using the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/), provided by Dell Inc. using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England and funding from the Science and Technology Facilities Council.This is the final version of the article. It first appeared from Springer via https://doi.org/10.1007/s10858-016-0062-

Capacity to make health care decisions: its importance in clinical practice

Background. Assessment of capacity plays a pivotal role in determining when decisions need to be made on behalf of an individual. It therefore has major clinical management implications for health care professionals and civil liberties implications for the person concerned. In many countries, there is a presumption that adults have the capacity to make health care decisions. However, in persons with a mental disability, capacity may be temporarily or permanently impaired. Methods. A selective review is presented which considers: (i) the broad approaches taken to determining capacity; (ii) the abilities commonly assessed in determining capacity; and (iii) the principles underlying health care decision-making for adults who are without capacity. Results. Capacity is a functional concept, determined by the person's ability to understand, retain, and weigh up information relevant to the decision in order to arrive at a choice, and then to communicate that choice. We have reviewed the studies that examined decision-making abilities in people with dementia, chronic mental illness or intellectual disabilities. Approaches to decision-making in adults who lack capacity include: anticipatory decisions made through advance health care statements or decisions by proxy based on ‘best interests’ or ‘substituted judgement’. Conclusions. The understanding of clinical and legal aspects of capacity is still developing. This paper examines current concepts of capacity and decision-making on behalf of those without capacity. We propose a framework, in line with current ethical and legal guidelines, as an aid to clinicians when they are seeking consent for a health care intervention.published_or_final_versio

Intramuscular Immunisation with Chlamydial Proteins Induces Chlamydia trachomatis Specific Ocular Antibodies.

BACKGROUND: Ocular infection with Chlamydia trachomatis can cause trachoma, which is the leading cause of blindness due to infection worldwide. Despite the large-scale implementation of trachoma control programmes in the majority of countries where trachoma is endemic, there remains a need for a vaccine. Since C. trachomatis infects the conjunctival epithelium and stimulates an immune response in the associated lymphoid tissue, vaccine regimens that enhance local antibody responses could be advantageous. In experimental infections of non-human primates (NHPs), antibody specificity to C. trachomatis antigens was found to change over the course of ocular infection. The appearance of major outer membrane protein (MOMP) specific antibodies correlated with a reduction in ocular chlamydial burden, while subsequent generation of antibodies specific for PmpD and Pgp3 correlated with C. trachomatis eradication. METHODS: We used a range of heterologous prime-boost vaccinations with DNA, Adenovirus, modified vaccinia Ankara (MVA) and protein vaccines based on the major outer membrane protein (MOMP) as an antigen, and investigated the effect of vaccine route, antigen and regimen on the induction of anti-chlamydial antibodies detectable in the ocular lavage fluid of mice. RESULTS: Three intramuscular vaccinations with recombinant protein adjuvanted with MF59 induced significantly greater levels of anti-MOMP ocular antibodies than the other regimens tested. Intranasal delivery of vaccines induced less IgG antibody in the eye than intramuscular delivery. The inclusion of the antigens PmpD and Pgp3, singly or in combination, induced ocular antigen-specific IgG antibodies, although the anti-PmpD antibody response was consistently lower and attenuated by combination with other antigens. CONCLUSIONS: If translatable to NHPs and/or humans, this investigation of the murine C. trachomatis specific ocular antibody response following vaccination provides a potential mouse model for the rapid and high throughput evaluation of future trachoma vaccines

Emergence of interaction effects in Bose-Einstein condensation

We present a quantitative evaluation of the predictions of mean-field theory for describing a Bose-Einstein condensate in a magnetic trap by comparing directly with experimental observations. We study the release energy from ballistic expansion and the cloud density profile as a function of mean-field effects. Significant departure of the cloud shape from both the noninteracting limit and the strongly repulsive limit is observed for our parameters, consistent with theoretical prediction

Risk factors for active trachoma in The Gambia.

Trachoma has been endemic in The Gambia for decades but national surveys indicate that the prevalence is falling. Risk factor data can help guide trachoma control efforts. This study investigated risk factors for active trachoma and ocular Chlamydia trachomatis infection in children aged below 10 years in two Gambian regions. The overall prevalence of C. trachomatis infection was only 0.3% (3/950) compared with 10.4% (311/2990) for active trachoma, therefore analyses were only performed for active trachoma. After adjustment, increased risk of trachoma was associated with being aged 1-2 years (odds ratio (OR) 2.20, 95% CI 1.07-4.52) and 3-5 years (OR 3.62, 95% CI 1.80-7.25) compared with <1 year, nasal discharge (OR 2.07, 95% CI 1.53-2.81), ocular discharge (OR 2.68, 95% CI 1.76-4.09) and there being at least one other child in the household with active trachoma (OR 11.28, 95% CI 8.31-15.31). Compared with other occupations, children of traders had reduced risk (OR 0.53, 95% CI 0.30-0.94). At the household level, only the presence of another child in the household with active trachoma was associated with increased risk of active trachoma, suggesting that current trachoma control interventions are effective at this level. In contrast, child-level factors were associated with increased risk after adjustment, indicating a need to increase control efforts at the child level

Increased Epithelial Expression of CTGF and S100A7 with Elevated Subepithelial Expression of IL-1 beta in Trachomatous Trichiasis

Purpose: To characterize the histological appearance and expression of pro-inflammatory mediators, growth factors, matrix metalloproteinases and biomarkers of epithelial-mesenchymal transition (EMT) in healthy control and trachomatous trichiasis (TT) conjunctival tissue. Methods: Conjunctival biopsies were taken from 20 individuals with TT and from 16 individuals with healthy conjunctiva, which served as controls. Study participants were of varying ethnicity and were living in a trachoma-endemic region of northern Tanzania. Formalin-fixed paraffin-embedded tissue sections were stained using hematoxylin and eosin or by immunohistochemistry using antibodies against: IL-1β, IL-6, IL-17A, IL-22, CXCL5, S100A7, cleaved caspase 1 (CC1), PDGF, CTGF, TGFβ2, MMP7, MMP9, E-cadherin, vimentin, and αSMA. Results: Tissue from TT cases had a greater inflammatory cell infiltrate relative to controls and greater disruption of collagen structure. CTGF and S100A7 were more highly expressed in the epithelium and IL-1β was more highly expressed in the substantia propria of TT cases relative to controls. Latent TGFβ2 was slightly more abundant in the substantia propria of control tissue. No differences were detected between TT cases and controls in the degree of epithelial atrophy, the number of myofibroblasts or expression of EMT biomarkers. Conclusions: These data indicate that the innate immune system is active in the immunopathology of trachoma, even in the absence of clinical inflammation. CTGF might provide a direct link between inflammation and fibrosis and could be a suitable target for therapeutic treatment to halt the progression of trachomatous scarring

Shaping the future for primary care education and training project. Finding the evidence for education & trainingto deliver integrated health & social care: A systematic review of the literature

This literature review is one of series of outputs from Shaping the Future in Primary Care Education and Trainingproject (www.pcet.org.uk) which is funded by the North WestDevelopment Agency (NWDA). It is the result of a collaborative initiative between the NWDA, the North WestUniversities Association and seven Higher Education Institutions in the North West of Englan

Metaproteomics reveals methyltransferases implicated in dichloromethane and glycine betaine fermentation by ‘Candidatus Formimonas warabiya’ strain DCMF

Dichloromethane (DCM; CH2Cl2) is a widespread pollutant with anthropogenic and natural sources. Anaerobic DCM-dechlorinating bacteria use the Wood–Ljungdahl pathway, yet dechlorination reaction mechanisms remain unclear and the enzyme(s) responsible for carbon-chlorine bond cleavage have not been definitively identified. Of the three bacterial taxa known to carry out anaerobic dechlorination of DCM, ‘Candidatus Formimonas warabiya’ strain DCMF is the only organism that can also ferment non-chlorinated substrates, including quaternary amines (i.e., choline and glycine betaine) and methanol. Strain DCMF is present within enrichment culture DFE, which was derived from an organochlorine-contaminated aquifer. We utilized the metabolic versatility of strain DCMF to carry out comparative metaproteomics of cultures grown with DCM or glycine betaine. This revealed differential abundance of numerous proteins, including a methyltransferase gene cluster (the mec cassette) that was significantly more abundant during DCM degradation, as well as highly conserved amongst anaerobic DCM-degrading bacteria. This lends strong support to its involvement in DCM dechlorination. A putative glycine betaine methyltransferase was also discovered, adding to the limited knowledge about the fate of this widespread osmolyte in anoxic subsurface environments. Furthermore, the metagenome of enrichment culture DFE was assembled, resulting in five high quality and two low quality draft metagenome-assembled genomes. Metaproteogenomic analysis did not reveal any genes or proteins for utilization of DCM or glycine betaine in the cohabiting bacteria, supporting the previously held idea that they persist via necromass utilization