Updating the DCC Curation Lifecycle Model

The DCC Curation Lifecycle Model has played a vital role in the field of data curation for over a decade. During that time, the scale and complexity of data have changed dramatically, along with the contexts of data production and use. This paper reports on a study examining factors impacting data curation practices and presents recommendations for updating the DCC Curation Lifecycle Model. The study was grounded in a review of other lifecycle models and informed by a site visit to the Digital Curation Centre and consultation with expert practitioners and researchers. Framed by contemporary conditions impacting the conduct of research and provision of data services, the analysis and proposed recommendations account for the prominence of machine-actionable data, the importance of machine learning for data processing and analytics, growth of integrated research workflows, and escalating concerns with fairness, accountability, and transparency of data and algorithms

Sialidases Affect the Host Cell Adherence and Epsilon Toxin-Induced Cytotoxicity of Clostridium perfringens Type D Strain CN3718

Clostridium perfringens type B or D isolates, which cause enterotoxemias or enteritis in livestock, produce epsilon toxin (ETX). ETX is exceptionally potent, earning it a listing as a CDC class B select toxin. Most C. perfringens strains also express up to three different sialidases, although the possible contributions of those enzymes to type B or D pathogenesis remain unclear. Type D isolate CN3718 was found to carry two genes (nanI and nanJ) encoding secreted sialidases and one gene (nanH) encoding a cytoplasmic sialidase. Construction in CN3718 of single nanI, nanJ and nanH null mutants, as well as a nanI/nanJ double null mutant and a triple sialidase null mutant, identified NanI as the major secreted sialidase of this strain. Pretreating MDCK cells with NanI sialidase, or with culture supernatants of BMC206 (an isogenic CN3718 etx null mutant that still produces sialidases) enhanced the subsequent binding and cytotoxic effects of purified ETX. Complementation of BMC207 (an etx/nanH/nanI/nanJ null mutant) showed this effect is mainly attributable to NanI production. Contact between BMC206 and certain mammalian cells (e.g., enterocyte-like Caco-2 cells) resulted in more rapid sialidase production and this effect involved increased transcription of BMC206 nanI gene. BMC206 was shown to adhere to some (e.g. Caco-2 cells), but not all mammalian cells, and this effect was dependent upon sialidase, particularly NanI, expression. Finally, the sialidase activity of NanI (but not NanJ or NanH) could be enhanced by trypsin. Collectively these in vitro findings suggest that, during type D disease originating in the intestines, trypsin may activate NanI, which (in turn) could contribute to intestinal colonization by C. perfringens type D isolates and also increase ETX action

Childhood Lead Poisoning

Although lead encephalopathy is rare, lead intoxication continues to be a significant problem in Detroit. Neuropsychological effects may occur even at low levels of lead. Since treatment of lead poisoning consists of a painful series of injections, it is imperative that more attention be given to the prevention of this disease. To confirm the magnitude of the problems, our experience with lead poisoning during a three-year period at Henry Ford Hospital\u27s Pediatric Department is reviewed

Manipulation of drugs to achieve the required dose is intrinsic to paediatric practice but is not supported by guidelines or evidence

Background: A lack of age-appropriate formulations can make it difficult to administer medicines to children. A manipulation of the dosage form may be required to achieve the required dose. This study aimed to describe medicines that are manipulated to achieve the required dose in paediatric practice.Method: A structured, undisguised observational study and postal survey. The observational study investigated drug manipulations occurring in clinical practice across three sites. The questionnaire, administered to a sample of paediatric nurses throughout the UK, surveyed manipulations conducted and nurses' experiences and views.Results: The observational study identified 310 manipulations, of which 62% involved tablets, 21% were intravenous drugs and 10% were sachets. Of the 54 observed manipulations 40 involved tablets with 65% of the tablets being cut and 30% dispersed to obtain a smaller dose. 188 manipulations were reported by questionnaire respondents, of these 46% involved tablets, 12% were intravenous drugs, and 12% were nebuliser solutions. Manipulations were predominantly, but not exclusively, identified in specialist clinical areas with more highly dependent patients. Questionnaire respondents were concerned about the accuracy of the dose achieved following manipulations and the lack of practice guidance.Conclusion: Manipulations to achieve the required dose occur throughout paediatric in-patient settings. The impact of manipulations on the efficacy of the drugs, the accuracy of the dose and any adverse effects on patients is not known. There is a need to develop evidence-based guidance for manipulations of medicines in children

Living with a left ventricular assist device:Capturing recipients experiences using group concept mapping software

BackgroundLeft ventricular assist device (LVAD) implantation significantly impacts on a recipient's symptoms and quality of life. Capturing their experiences and post implant journey is an important part of clinical practice, research and device design evolution. Patient reported outcome measures (PROMs) are a useful tool for capturing that experience. However, patient reported outcome measures need to reflect recipients' experiences. Discussions with a patient partner group found that none of the frequently used cardiology PROMs captured their unique experiences.AimsTo capture the experiences and important issues for LVAD recipients. Develop a conceptual map of domains and items that should be reflected in patient reported outcomes.MethodsGroup concept mapping (GCM) web-based software was used to remotely capture and structure recipients' experiences across a wide geographical area. GCM is a semi-quantitative mixed method consisting of 3 stages: item generation, item sorting and rating (importance, relevance and frequency). Patient partners were involved in all aspects of the study design and development.Results18 LVAD recipients consented to take part. 101 statements were generated and multi-dimensional scaling, and hierarchical cluster analysis identified 9 clusters. Cluster themes included: Activities, Partner/family support, Travel, Mental wellbeing, Equipment and clothing, Physical and cognitive limitations, LVAD Restrictions, LVAD Challenges and positive impact of the LVAD (LVAD Positives). LVAD Positives were scored highest across all the rating variables, e.g., frequency (2.85), relevance (2.44) and importance (2.21). Other domains rated high for importance included physical and cognitive limitations (2.19), LVAD restrictions (2.11), Partner/family support (2.02), and Equipment and clothing (2.01).ConclusionOnline GCM software facilitated the inclusion of geographically dispersed recipients and provided useful insights into the experiences of LVAD recipients. The conceptual framework identifies important domains and items that should be prioritised and included in patient reported outcomes in future research, LVAD design evolution, and clinical practice

Controlled meal frequency without caloric restriction alters peripheral blood mononuclear cell cytokine production

<p>Abstract</p> <p>Background</p> <p>Intermittent fasting (IF) improves healthy lifespan in animals by a mechanism involving reduced oxidative damage and increased resistance to stress. However, no studies have evaluated the impact of controlled meal frequency on immune responses in human subjects.</p> <p>Objective</p> <p>A study was conducted to establish the effects of controlled diets with different meal frequencies, but similar daily energy intakes, on cytokine production in healthy male and female subjects.</p> <p>Design</p> <p>In a crossover study design with an intervening washout period, healthy normal weight middle-age male and female subjects (n = 15) were maintained for 2 months on controlled on-site one meal per day (OMD) or three meals per day (TMD) isocaloric diets. Serum samples and peripheral blood mononuclear cells (PBMCs) culture supernatants from subjects were analyzed for the presence of inflammatory markers using a multiplex assay.</p> <p>Results</p> <p>There were no significant differences in the inflammatory markers in the serum of subjects on the OMD or TMD diets. There was an increase in the capacity of PBMCs to produce cytokines in subjects during the first month on the OMD or TMD diets.</p> <p>Lower levels of TNF-α, IL-17, MCP-1 and MIP-1β were produced by PBMCs from subjects on the OMD versus TMD diet.</p> <p>Conclusions</p> <p>PBMCs of subjects on controlled diets exhibit hypersensitivities to cellular stimulation suggesting that stress associated with altered eating behavior might affect cytokine production by immune cells upon stimulation. Moreover, stimulated PBMCs derived from healthy individuals on a reduced meal frequency diet respond with a reduced capability to produce cytokines.</p

A quantitative structure- property relationship of gas chromatographic/mass spectrometric retention data of 85 volatile organic compounds as air pollutant materials by multivariate methods

A quantitative structure-property relationship (QSPR) study is suggested for the prediction of retention times of volatile organic compounds. Various kinds of molecular descriptors were calculated to represent the molecular structure of compounds. Modeling of retention times of these compounds as a function of the theoretically derived descriptors was established by multiple linear regression (MLR) and artificial neural network (ANN). The stepwise regression was used for the selection of the variables which gives the best-fitted models. After variable selection ANN, MLR methods were used with leave-one-out cross validation for building the regression models. The prediction results are in very good agreement with the experimental values. MLR as the linear regression method shows good ability in the prediction of the retention times of the prediction set. This provided a new and effective method for predicting the chromatography retention index for the volatile organic compounds

Absence of the Long Head of the Biceps Tendon Associated With Glenoid Dysplasia and Posterior Labral Tear

] J. Bone Joint Surg. . To the authors&apos; knowledge, there have been only five reported cases of congenital absence of the long head of the biceps tendon. Three of these cases were associated with anterior shoulder instability, one with a superior labral anterior posterior lesion and one simply with shoulder pain. This is the first reported case of congenital absence of the biceps tendon associated with glenoid dysplasia and a posterior labral tear. Clin. Anat. 21:728-732, 2008. V V C 2008 Wiley-Liss, Inc

Cardiac expression of the cystic fibrosis transmembrane conductance regulator involves novel Exon 1 usage to produce a unique amino-terminal protein

Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a chloride channel present in many cells. In cardiomyocytes, we report that multiple exon 1 usage and alternative splicing produces four CFTR transcripts, with different 5'-untranslated regions, CFTRTRAD-139, CFTR-1C/-1A, CFTR-1C, and CFTR-1B. CFTR transcripts containing the novel upstream exons (exons -1C, -1B, and -1A) represent more than 90% of cardiac expressed CFTR mRNA. Regulation of cardiac CFTR expression, in response to developmental and pathological stimuli, is exclusively due to the modulation of CFTR-1C and CFTR-1C/-1A expression. Upstream open reading frames have been identified in the 5'-untranslated regions of all CFTR transcripts that, in conjunction with adjacent stem-loop structures, modulate the efficiency of translation initiation at the AUG codon of the main CFTR coding region in CFTRTRAD-139 and CFTR-1C/-1A transcripts. Exon(-1A), only present in CFTR-1C/-1A transcripts, encodes an AUG codon that is in-frame with the main CFTR open reading frame, the efficient translation of which produces a novel CFTR protein isoform with a curtailed amino terminus. As the expression of this CFTR transcript parallels the spatial and temporal distribution of the cAMP-activated whole-cell current density in normal and diseased hearts, we suggest that CFTR-1C/-1A provides the molecular basis for the cardiac cAMP-activated chloride channel. Our findings provide further insight into the complex nature of in vivo CFTR expression, to which multiple mRNA transcripts, protein isoforms, and post-transcriptional regulatory mechanisms are now added