Derivation and internal validation of an equation for albumin-adjusted calcium

YesFunding provided by the Open Access Authors Fund

Morphometrical analysis of transbronchial cryobiopsies

The recent introduction of bronchoscopically recovered cryobiopsy of lung tissue has opened up new possibilities in the diagnosis of neoplastic and non-neoplastic lung diseases in various aspects. Most notably the morphological diagnosis of peripheral lung biopsies promises to achieve a better yield with a high quality of specimens. To better understand this phenomenon, its diagnostic options and perspectives, this study morphometrically compares 15 cryobiopsies and 18 transbronchial forceps biopsies of peripheral lung tissue a priori without considering clinical hit ratio or integration of results in the clinical diagnostic processing. Cryotechnically harvested specimens were significantly larger (mean: 17.1 ± 10.7 mm2 versus 3.8 ± 4.0 mm2) and contained alveolar tissue more often. If present, the alveolar part in cryobiopsies exceeded the one of forceps biopsies. The alveolar tissue of crybiopsy specimens did not show any artefacts. Based on these results cryotechnique seems to open up new perspectives in bronchoscopic diagnosis of lung disease

Murine Pancreatic Adenocarcinoma Reduces Ikaros Expression and Disrupts T Cell Homeostasis

Background Maintenance of T cell immune homeostasis is critical for adequate anti-tumor immunity. The transcription factor Ikaros is essential for lymphocyte development including T cells. Alterations in Ikaros expression occur in blood malignancies in humans and mice. In this study, we investigated the role of Ikaros in regulating T cell immune balance in pancreatic cancer mouse models. Methodology and Principal Findings Using our Panc02 tumor-bearing (TB) mouse model, western blot analysis revealed a reduction in Ikaros proteins while qRT-PCR showed no differences in Ikaros mRNA levels in TB splenocytes compared to control. Treatment of naïve splenocytes with the proteasomal inhibitor, MG132, stabilized Ikaros expression and prevented Ikaros downregulation by Panc02 cells, in vitro. Western blot analyses showed a reduction in protein phosphatase 1 (PP1) and protein kinase CK2 expression in TB splenocytes while CK2 activity was increased. Immunofluorescence microscopy revealed altered punctate staining of Ikaros in TB splenocytes. Flow cytometry revealed a significant decrease in effector CD4+ and CD8+ T cell percentages but increased CD4+CD25+ regulatory T cells in TB splenocytes. Similar alterations in T cell percentages, as well as reduced Ikaros and CK2 but not PP1 expression, were observed in a transgenic, triple mutant (TrM) pancreatic cancer model. Ikaros expression was also reduced in enriched TB CD3+ T cells. MG132 treatment of naïve CD3+ T cells stabilized Ikaros expression in the presence of Panc02 cells. Western blots showed reduced PP1 and CK2 expression in TB CD3+ T cells. Conclusions/Significance The results of this study suggest that the pancreatic tumor microenvironment may cause proteasomal degradation of Ikaros, possibly via dysregulation of PP1 and CK2 expression and activity, respectively. This loss of Ikaros expression may contribute to an imbalance in T cell percentages. Ikaros may potentially be a therapeutic target to restore T cell homeostasis in pancreatic cancer hosts, which may be critical for effective anti-tumor immunity

Factors associated with self-care activities among adults in the United Kingdom: a systematic review

Background: The Government has promoted self-care. Our aim was to review evidence about who uses self-tests and other self-care activities (over-the-counter medicine, private sector,complementary and alternative medicine (CAM), home blood pressure monitors). Methods: During April 2007, relevant bibliographic databases (Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Applied Social Sciences Index and Abstracts, PsycINFO,British Nursing Index, Allied and Complementary Medicine Database, Sociological Abstracts, International Bibliography of the Social Sciences, Arthritis and Complementary Medicine Database, Complementary and Alternative Medicine and Pain Database) were searched, and potentially relevant studies were reviewed against eligibility criteria. Studies were included if they were published during the last 15 years and identified factors, reasons or characteristics associated with a relevant activity among UK adults. Two independent reviewers used proformas to assess the quality of eligible studies. Results: 206 potentially relevant papers were identified, 157 were excluded, and 49 papers related to 46 studies were included: 37 studies were, or used data from questionnaire surveys, 36 had quality scores of five or more out of 10, and 27 were about CAM. Available evidence suggests that users of CAM and over-the-counter medicine are female, middle-aged, affluent and/or educated with some measure of poor health, and that people who use the private sector are affluent and/or educated. Conclusion: People who engage in these activities are likely to be affluent. Targeted promotion may, therefore, be needed to ensure that use is equitable. People who use some activities also appear to have poorer measures of health than non-users or people attending conventional services. It is, therefore, also important to ensure that self-care is not used as a second choice for people who have not had their needs met by conventional service

The Retinoic Acid Receptor Agonist Am80 Increases Mucosal Inflammation in an IL-6 Dependent Manner During Trichuris muris Infection

PURPOSE: Vitamin A metabolites, such as all-trans-retinoic acid (RA) that act through the nuclear receptor; retinoic acid receptor (RAR), have been shown to polarise T cells towards Th2, and to be important in resistance to helminth infections. Co-incidentally, people harbouring intestinal parasites are often supplemented with vitamin A, as both vitamin A deficiency and parasite infections often occur in the same regions of the globe. However, the impact of vitamin A supplementation on gut inflammation caused by intestinal parasites is not yet completely understood. METHODS: Here, we use Trichuris muris, a helminth parasite that buries into the large intestine of mice causing mucosal inflammation, as a model of both human Trichuriasis and IBD, treat with an RARα/β agonist (Am80) and quantify the ensuing pathological changes in the gut. RESULTS: Critically, we show, for the first time, that rather than playing an anti-inflammatory role, Am80 actually exacerbates helminth-driven inflammation, demonstrated by an increased colonic crypt length and a significant CD4(+) T cell infiltrate. Further, we established that the Am80-driven crypt hyperplasia and CD4(+) T cell infiltrate were dependent on IL-6, as both were absent in Am80-treated IL-6 knock-out mice. CONCLUSIONS: This study presents novel data showing a pro-inflammatory role of RAR ligands in T. muris infection, and implies an undesirable effect for the administration of vitamin A during chronic helminth infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10875-013-9936-8) contains supplementary material, which is available to authorized users

From DNA sequence to application: possibilities and complications

The development of sophisticated genetic tools during the past 15 years have facilitated a tremendous increase of fundamental and application-oriented knowledge of lactic acid bacteria (LAB) and their bacteriophages. This knowledge relates both to the assignments of open reading frames (ORF’s) and the function of non-coding DNA sequences. Comparison of the complete nucleotide sequences of several LAB bacteriophages has revealed that their chromosomes have a fixed, modular structure, each module having a set of genes involved in a specific phase of the bacteriophage life cycle. LAB bacteriophage genes and DNA sequences have been used for the construction of temperature-inducible gene expression systems, gene-integration systems, and bacteriophage defence systems. The function of several LAB open reading frames and transcriptional units have been identified and characterized in detail. Many of these could find practical applications, such as induced lysis of LAB to enhance cheese ripening and re-routing of carbon fluxes for the production of a specific amino acid enantiomer. More knowledge has also become available concerning the function and structure of non-coding DNA positioned at or in the vicinity of promoters. In several cases the mRNA produced from this DNA contains a transcriptional terminator-antiterminator pair, in which the antiterminator can be stabilized either by uncharged tRNA or by interaction with a regulatory protein, thus preventing formation of the terminator so that mRNA elongation can proceed. Evidence has accumulated showing that also in LAB carbon catabolite repression in LAB is mediated by specific DNA elements in the vicinity of promoters governing the transcription of catabolic operons. Although some biological barriers have yet to be solved, the vast body of scientific information presently available allows the construction of tailor-made genetically modified LAB. Today, it appears that societal constraints rather than biological hurdles impede the use of genetically modified LAB.

Volcanic impacts on the Holocene vegetation history of Britain and Ireland? A review and meta-analysis of the pollen evidence

Volcanic ash layers show that the products of Icelandic volcanism reached Britain and Ireland many times during the Holocene. Historical records suggest that at least one eruption, that of Laki in a.d. 1783, was associated with impacts on vegetation. These results raise the question: did Icelandic volcanism affect the Holocene vegetation history of Britain and Ireland? Several studies have used pollen data to address this issue but no clear consensus has been reached. We re-analyse the palynological data using constrained ordination with various representations of potential volcanic impacts. We find that the palynological evidence for volcanic impacts on vegetation is weak but suggest that this is a case of absence of evidence and is not necessarily evidence of absence of impact. To increase the chances of identifying volcanic impacts, future studies need to maximise temporal resolution, replicate results, and investigate a greater number of tephras in a broader range of locations, including more studies from lake sediments

Multi-factor service design: identification and consideration of multiple factors of the service in its design process

Service design is a multidisciplinary area that helps innovate services by bringing new ideas to customers through a design-thinking approach. Services are affected by multiple factors, which should be considered in designing services. In this paper, we propose the multi-factor service design (MFSD) method, which helps consider the multi-factor nature of service in the service design process. The MFSD method has been developed through and used in five service design studies with industry and government. The method addresses the multi-factor nature of service for systematic service design by providing the following guidelines: (1) identify key factors that affect the customer value creation of the service in question (in short, value creation factors), (2) define the design space of the service based on the value creation factors, and (3) design services and represent them based on the factors. We provide real stories and examples from the five service design studies to illustrate the MFSD method and demonstrate its utility. This study will contribute to the design of modern complex services that are affected by varied factors

A UMLS-based spell checker for natural language processing in vaccine safety

BACKGROUND: The Institute of Medicine has identified patient safety as a key goal for health care in the United States. Detecting vaccine adverse events is an important public health activity that contributes to patient safety. Reports about adverse events following immunization (AEFI) from surveillance systems contain free-text components that can be analyzed using natural language processing. To extract Unified Medical Language System (UMLS) concepts from free text and classify AEFI reports based on concepts they contain, we first needed to clean the text by expanding abbreviations and shortcuts and correcting spelling errors. Our objective in this paper was to create a UMLS-based spelling error correction tool as a first step in the natural language processing (NLP) pipeline for AEFI reports. METHODS: We developed spell checking algorithms using open source tools. We used de-identified AEFI surveillance reports to create free-text data sets for analysis. After expansion of abbreviated clinical terms and shortcuts, we performed spelling correction in four steps: (1) error detection, (2) word list generation, (3) word list disambiguation and (4) error correction. We then measured the performance of the resulting spell checker by comparing it to manual correction. RESULTS: We used 12,056 words to train the spell checker and tested its performance on 8,131 words. During testing, sensitivity, specificity, and positive predictive value (PPV) for the spell checker were 74% (95% CI: 74–75), 100% (95% CI: 100–100), and 47% (95% CI: 46%–48%), respectively. CONCLUSION: We created a prototype spell checker that can be used to process AEFI reports. We used the UMLS Specialist Lexicon as the primary source of dictionary terms and the WordNet lexicon as a secondary source. We used the UMLS as a domain-specific source of dictionary terms to compare potentially misspelled words in the corpus. The prototype sensitivity was comparable to currently available tools, but the specificity was much superior. The slow processing speed may be improved by trimming it down to the most useful component algorithms. Other investigators may find the methods we developed useful for cleaning text using lexicons specific to their area of interest