Modelling phosphorus fluxes in Loweswater

1. This is the final report to the Loweswater Care Project (in support of the Catchment Restoration Fund for England) ECRC-ENSIS Project 298, 'Loweswater 12-13'. The study was concerned with the spatial and temporal concentrations of sediment phosphorus (P) in the lake and the use of P measurements from the water column and inflow and outflow samples to derive a simple mass balance model for P in the lake. 2. A review of published and unpublished literature on Loweswater highlighted trends in water chemistry since the mid-eighteenth century. Land use and farming practises have changed over the past 200 years which have led to increased nutrient loading to the lake with significant increases occurring in the mid part of the last century. Agricultural intensification is likely to be a significant cause of the problem as well as inadequate septic tank management. Local management efforts, led by the Loweswater Care Project, has sought to reduce the primary sources of nutrients reaching the lake, but total phosphorus (TP) concentrations in the lake remain higher than desired. 3. Temperature and dissolved oxygen (DO) profiling confirmed that the site stratified in summer with major changes in DO occurring below a depth of 8 m. The deeper waters were almost entirely anoxic. During stratification the maximum TP value was recorded at the lake bottom. This is a clear indication that P is being released from the lake bed during summer stratification. 4. Analysis of the stream water from the Dub Beck inflow (data for 2013), shows that P influx remains high enough to explain the elevated lake water P concentrations, despite considerable efforts to reduce catchment P sources. 5. Analysis of the water column P profiles shows that P release from the sediment is only a minor contribution to the P load. While the sediment core data reveals a substantial pool of P in the sediment very little of this should be released each year to the water column. In 2013 it is estimated that more than 90% of the P came from the catchment and only ~10% from the sediment. 6. As with all modelling exercises there are uncertainties inherent in the approach. In this case the model output is based on a single year of input data for the inflow P flux calculations and it would be preferable to have a longer data series to inform the modelling. Inflow fluxes are highly dependent on flow conditions and here, in the absence of flow data from Dub Beck, we used data from a nearby stream. Further, the monthly sampling has resulted in most samples being taken in low flow conditions, thus missing potential storm flow conditions. Finally, stream input information is restricted to Dub Beck, and contributions from the other stream is unknown. 7. Nevertheless, the results from the modelling are clear and on that basis we conclude that the priority is for P loading to the lake to be reduced by better catchment management and that lake manipulation is not warranted. Integrated catchment management supported by modelling together with local stakeholder engagement should provide the most effective means of improving the condition of the lake

Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G

Background: The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised. Methodology/Principal Findings: We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy. Conclusions/Significance: We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality

Differential viral accessibility (DIVA) identifies alterations in chromatin architecture through large-scale mapping of lentiviral integration sites.

Alterations in chromatin structure play a major role in the epigenetic regulation of gene expression. Here, we describe a step-by-step protocol for differential viral accessibility (DIVA), a method for identifying changes in chromatin accessibility genome-wide. Commonly used methods for mapping accessible genomic loci have strong preferences toward detecting 'open' chromatin found at regulatory regions but are not well suited to studying chromatin accessibility in gene bodies and intergenic regions. DIVA overcomes this limitation, enabling a broader range of sites to be interrogated. Conceptually, DIVA is similar to ATAC-seq in that it relies on the integration of exogenous DNA into the genome to map accessible chromatin, except that chromatin architecture is probed through mapping integration sites of exogenous lentiviruses. An isogenic pair of cell lines are transduced with a lentiviral vector, followed by PCR amplification and Illumina sequencing of virus-genome junctions; the resulting sequences define a set of unique lentiviral integration sites, which are compared to determine whether genomic loci exhibit significantly altered accessibility between experimental and control cells. Experienced researchers will take 6 d to generate lentiviral stocks and transduce the target cells, a further 5 d to prepare the Illumina sequencing libraries and a few hours to perform the bioinformatic analysis

Status and perspectives of hospital mortality in a public urban Hellenic hospital, based on a five-year review

<p>Abstract</p> <p>Background</p> <p>Analysis of hospital mortality helps to assess the standards of health-care delivery.</p> <p>Methods</p> <p>This is a retrospective cohort study evaluating the causes of deaths which occurred during the years 1995–1999 in a single hospital. The causes of death were classified according to the International Statistical Classification of Diseases (ICD-10).</p> <p>Results</p> <p>Of the 149,896 patients who were discharged the 5836 (3.4%) died. Males constituted 55% and females 45%. The median age was 75.1 years (1 day – 100 years).</p> <p>The seven most common ICD-10 chapters IX, II, IV, XI, XX, X, XIV included 92% of the total 5836 deaths.</p> <p>The most common contributors of non-neoplasmatic causes of death were cerebrovascular diseases (I60–I69) at 15.8%, ischemic heart disease (I20–I25) at 10.3%, cardiac failure (I50.0–I50.9) at 7.9%, diseases of the digestive system (K00–K93) at 6.7%, diabetes mellitus (E10–E14) at 6.6%, external causes of morbidity and mortality (V01–Y98) at 6.2%, renal failure (N17–N19) at 4.5%, influenza and pneumonia (J10–J18) at 4.1% and certain infectious and parasitic diseases (A00–B99) at 3.2%, accounting for 65.3% of the total 5836 deaths.</p> <p>Neoplasms (C00–D48) caused 17.7% (n = 1027) of the total 5836 deaths, with leading forms being the malignant neoplasms of bronchus and lung (C34) at 3.5% and the malignant neoplasms of large intestine (C18–21.2) at 1.5%. The highest death rates occurred in the intensive care unit (23.3%), general medicine (10.7%), cardiology (6.5%) and nephrology (5.5%).</p> <p>Key problems related to certification of death were identified. Nearly half of the deaths (49.3%: n = 2879) occurred by the completion of the third day, which indicates the time limits for investigation and treatment. On the other hand, 6% (n = 356) died between the 29^thand 262^nddays after admission.</p> <p>Inadequacies of the emergency care service, infection control, medical oncology, rehabilitation, chronic and terminal care facilities, as well as lack of regional targets for reducing mortality related to diabetes, recruitment of organ donors, provision for the aging population and lack of prevention programs were substantiated.</p> <p>Conclusion</p> <p>Several important issues were raised. Disease specific characteristics, as well as functional and infrastructural inadequacies were identified and provided evidence for defining priorities and strategies for improving the standards of care. Effective transformation can promise better prospects.</p

The past, present and future of Scientific discourse.

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