Functional and physiological role of vitamin C transporters

Vitamin C (ascorbic acid) is required for the synthesis of collagen, carnitine, catecholamine and the neurotransmitter norepinephrine. Vitamin C also plays an important role in protection against oxidative stress. Transporters for vitamin C and its oxidized form dehydroascorbate (DHA) are crucial to keep vitamin concentrations optimal in the body. The human SLC23 family consists of the Na(+)-dependent vitamin C transporters SVCT1 (SLC23A1) and SVCT2 (SLC23A2) and the orphan transporter SVCT3 (SLC23A3). Phylogenetically, the SLC23 family belongs to the nucleobase-ascorbate transporter family although no specificity for nucleobases has yet been demonstrated for the human members of this family. In fact, the SVCT1 and SVCT2 transporters are rather specific for ascorbic acid. SVCT1 is expressed in epithelial tissues such as intestine, where it contributes to the maintenance of whole-body ascorbic acid levels, whereas the expression of SVCT2 is relatively widespread either to protect metabolically active cells and specialized tissues from oxidative stress or to deliver ascorbic acid to tissues that are in high demand of the vitamin for enzymatic reactions. DHA, the oxidized form of ascorbic acid is taken up and distributed in the body by facilitated transport via members of the SLC2/GLUT family (GLUT1, GLUT3, and GLUT4). Although, the main focus of this review is on the SLC23 family of ascorbic acid transporters, transporters of DHA and nucleobases are also briefly discussed for completeness.

[The model project "newborn auditory screening" in the Upper Palatinate: high process and result quality of an interdisciplinary concept]

BACKGROUND: In May 2003, a newborn auditory screening program was initiated in the Upper Palatinate. METHODS: Sequential OAE- and BERA-screening was conducted in all hospitals with obstetric facilities. The Screening Center at the Public Health Authority was responsible for the coordination of the screening process, completeness of participation, the follow-up of all subjects with a positive screening test and the quality of instrumental screening. RESULTS: A total of 96% of 17,469 newborns were screened. The referral rate at discharge was 1.6% (0.4% for bilateral positive findings). For 97% of the positive screening results, a definite diagnosis to confirm or exclude hearing loss was achieved; for 43% only after intervention by the Screening Center. Fifteen children with profound bilateral hearing impairment were identified of whom eight were only detected by the intervention of the Screening Center. CONCLUSION: The effective structures established in the Upper Palatinate provide a standard for the quality of neonatal auditory screening achievable in Germany.

Incidence of childhood cancer in Switzerland: the Swiss Childhood Cancer Registry

BACKGROUND: This report describes the incidence of childhood cancer in Switzerland, based on the data from the Swiss Childhood Cancer Registry (SCCR), a national hospital-based cancer registry with very high coverage, founded in 1976 by the Swiss Paediatric Oncology Group (SPOG). PROCEDURE: Malignancies were coded according to the International Classification of Childhood Cancer (ICCC-3). Incidence rates per 100,000 person-years were calculated for all malignancies and groups of malignancies in Swiss residents less than 15 years of age for the decade 1995-2004. RESULTS: The SCCR annually registered on average 174 new cases of cancer in Swiss residents aged <15 years, with a median age at diagnosis of 5.6 years. The crude incidence of childhood cancer in children aged <15 years was 13.5, higher for boys (15.0 per 100,000) than for girls (12.1 per 100,000), and was nearly twice as high in the first 5 years of life (19.3 per 100,000) than in the age group 5 to 14 years (10.8 per 100,000). CONCLUSION: Incidence of childhood cancers in the SCCR was similar to neighbouring countries and to data published by regional cancer registries in Switzerland for the same period, suggesting good completeness of registration. This makes the SCCR a valuable resource for national and international research on childhood cancer.

Inducible endothelial cell-specific gene expression in transgenic mouse embryos and adult mice

Utilizing both the TET-OFF and TET-ON systems in combination with transcriptional control elements of the Tie-2 gene, we have established a series of transgenic activator and responder mice for TET-regulated endothelial cell-specific transgene expression in double transgenic mouse embryos and in adult mice. TET-regulated expression of LacZ reporter genes could be achieved in virtually all endothelia in mid gestation stage mouse embryos. In contrast in adult mice, using the very same Tie-2 tTA activator mouse strain, we observed striking differences of TET-induced gene expression from various inducible expression constructs in different vascular beds. Non-endothelial expression was never detected. The prominent differences in completeness of TET-induced endothelial expression highlight the still underestimated critical role of the responder mouse lines for uniform TET-induced gene expression in heterogeneous cell populations such as endothelial cells. Interestingly, in double transgenic mice inducibly expressing several different adhesion molecules, no adverse effects were observed even though these proteins were robustly expressed on endothelial cells in adult tissues. These transgenic model systems provide versatile tools for the TET-regulated manipulation of endothelial cell-specific gene expression in the entire embryonic vasculature and distinct vascular beds in adult mice.

Individual patient data meta-analysis of diagnostic and prognostic studies in obstetrics, gynaecology and reproductive medicine

BACKGROUND: In clinical practice a diagnosis is based on a combination of clinical history, physical examination and additional diagnostic tests. At present, studies on diagnostic research often report the accuracy of tests without taking into account the information already known from history and examination. Due to this lack of information, together with variations in design and quality of studies, conventional meta-analyses based on these studies will not show the accuracy of the tests in real practice. By using individual patient data (IPD) to perform meta-analyses, the accuracy of tests can be assessed in relation to other patient characteristics and allows the development or evaluation of diagnostic algorithms for individual patients. In this study we will examine these potential benefits in four clinical diagnostic problems in the field of gynaecology, obstetrics and reproductive medicine. METHODS/DESIGN: Based on earlier systematic reviews for each of the four clinical problems, studies are considered for inclusion. The first authors of the included studies will be invited to participate and share their original data. After assessment of validity and completeness the acquired datasets are merged. Based on these data, a series of analyses will be performed, including a systematic comparison of the results of the IPD meta-analysis with those of a conventional meta-analysis, development of multivariable models for clinical history alone and for the combination of history, physical examination and relevant diagnostic tests and development of clinical prediction rules for the individual patients. These will be made accessible for clinicians. DISCUSSION: The use of IPD meta-analysis will allow evaluating accuracy of diagnostic tests in relation to other relevant information. Ultimately, this could increase the efficiency of the diagnostic work-up, e.g. by reducing the need for invasive tests and/or improving the accuracy of the diagnostic workup. This study will assess whether these benefits of IPD meta-analysis over conventional meta-analysis can be exploited and will provide a framework for future IPD meta-analyses in diagnostic and prognostic research.

Ecological explanations for (incomplete) speciation

Divergent natural selection has been shown to promote speciation in many taxa. However, although divergent selection often initiates the process of speciation, it often fails to complete it. Several time-based, geographic and genetic factors have been recognized to explain this variability in how far speciation proceeds. We review here recent evidence indicating that variability in the completeness of speciation can also be associated with the nature of divergent selection itself, with speciation being greatly promoted by (i) stronger selection on a given, single trait (the 'stronger selection' hypothesis) and (ii) selection on a greater number of traits (the 'multifarious selection' hypothesis). However, evidence for each selective hypothesis is still scarce, and further work is required to determine their relative importance.

Reporting quality of systematic review abstracts in leading oral implantology journals

OBJECTIVES Abstracts of systematic reviews are of critical importance, as consumers of research often do not access the full text. This study aimed to assess the reporting quality of systematic review (SR) abstracts in leading oral implantology journals. METHODS Six specialty journals were screened for SRs between 2008 and 2012. A 16-item checklist, based on the PRISMA statement, was used to examine the completeness of abstract reporting. RESULTS Ninety-three SR abstracts were included in this study. The majority were published in Clinical Oral Implants Research (43%). The mean overall reporting quality score was 72.5% (95% CI: 70.8-74.2). Most abstracts were structured (97.9%), adequately reporting objectives (97.9%) and conclusions (93.6%). Conversely, inadequate reporting of methods of the study, background (79.6%), appraisal (65.6%), and data synthesis (65.6%) were observed. Registration of reviews was not reported in any of the included abstracts. Multivariate analysis revealed no difference in reporting quality with respect to continent, number of authors, or meta-analysis conduct. CONCLUSIONS The results of this study suggest that the reporting quality of systematic review abstracts in implantology journals requires further improvement. CLINICAL SIGNIFICANCE Better reporting of SR abstracts is particularly important in ensuring the reliability of research findings, ultimately promoting the practice of evidence-based dentistry. Optimal reporting of SR abstracts should be encouraged, preferably by endorsing the PRISMA for abstracts guidelines.

Data quality of animal health records on Swiss dairy farms

High-quality data are essential for veterinary surveillance systems, and their quality can be affected by the source and the method of collection. Data recorded on farms could provide detailed information about the health of a population of animals, but the accuracy of the data recorded by farmers is uncertain. The aims of this study were to evaluate the quality of the data on animal health recorded on 97 Swiss dairy farms, to compare the quality of the data obtained by different recording systems, and to obtain baseline data on the health of the animals on the 97 farms. Data on animal health were collected from the farms for a year. Their quality was evaluated by assessing the completeness and accuracy of the recorded information, and by comparing farmers' and veterinarians' records. The quality of the data provided by the farmers was satisfactory, although electronic recording systems made it easier to trace the animals treated. The farmers tended to record more health-related events than the veterinarians, although this varied with the event considered, and some events were recorded only by the veterinarians. The farmers' attitude towards data collection was positive. Factors such as motivation, feedback, training, and simplicity and standardisation of data collection were important because they influenced the quality of the data.

Admissibility in Finitely Generated Quasivarieties

Checking the admissibility of quasiequations in a finitely generated (i.e., generated by a finite set of finite algebras) quasivariety Q amounts to checking validity in a suitable finite free algebra of the quasivariety, and is therefore decidable. However, since free algebras may be large even for small sets of small algebras and very few generators, this naive method for checking admissibility in Q is not computationally feasible. In this paper, algorithms are introduced that generate a minimal (with respect to a multiset well-ordering on their cardinalities) finite set of algebras such that the validity of a quasiequation in this set corresponds to admissibility of the quasiequation in Q. In particular, structural completeness (validity and admissibility coincide) and almost structural completeness (validity and admissibility coincide for quasiequations with unifiable premises) can be checked. The algorithms are illustrated with a selection of well-known finitely generated quasivarieties, and adapted to handle also admissibility of rules in finite-valued logics.

A Finite Model Property for Gödel Modal Logics

A new semantics with the finite model property is provided and used to establish decidability for Gödel modal logics based on (crisp or fuzzy) Kripke frames combined locally with Gödel logic. A similar methodology is also used to establish decidability, and indeed co-NP-completeness for a Gödel S5 logic that coincides with the one-variable fragment of first-order Gödel logic.

The Swiss Neonatal Quality Cycle, a monitor for clinical performance and tool for quality improvement

BACKGROUND We describe the setup of a neonatal quality improvement tool and list which peer-reviewed requirements it fulfils and which it does not. We report on the so-far observed effects, how the units can identify quality improvement potential, and how they can measure the effect of changes made to improve quality. METHODS Application of a prospective longitudinal national cohort data collection that uses algorithms to ensure high data quality (i.e. checks for completeness, plausibility and reliability), and to perform data imaging (Plsek's p-charts and standardized mortality or morbidity ratio SMR charts). The collected data allows monitoring a study collective of very low birth-weight infants born from 2009 to 2011 by applying a quality cycle following the steps 'guideline - perform - falsify - reform'. RESULTS 2025 VLBW live-births from 2009 to 2011 representing 96.1% of all VLBW live-births in Switzerland display a similar mortality rate but better morbidity rates when compared to other networks. Data quality in general is high but subject to improvement in some units. Seven measurements display quality improvement potential in individual units. The methods used fulfil several international recommendations. CONCLUSIONS The Quality Cycle of the Swiss Neonatal Network is a helpful instrument to monitor and gradually help improve the quality of care in a region with high quality standards and low statistical discrimination capacity.

The reporting quality of randomized controlled trials in orthodontics.

OBJECTIVES Accurate trial reporting facilitates evaluation and better use of study results. The objective of this article is to investigate the quality of reporting of randomized controlled trials (RCTs) in leading orthodontic journals, and to explore potential predictors of improved reporting. METHODS The 50 most recent issues of 4 leading orthodontic journals until November 2013 were electronically searched. Reporting quality assessment was conducted using the modified CONSORT statement checklist. The relationship between potential predictors and the modified CONSORT score was assessed using linear regression modeling. RESULTS 128 RCTs were identified with a mean modified CONSORT score of 68.97% (SD = 11.09). The Journal of Orthodontics (JO) ranked first in terms of completeness of reporting (modified CONSORT score 76.21%, SD = 10.1), followed by American Journal of Orthodontics and Dentofacial Orthopedics (AJODO) (73.05%, SD = 10.1). Journal of publication (AJODO: β = 10.08, 95% CI: 5.78, 14.38; JO: β = 16.82, 95% CI: 11.70, 21.94; EJO: β = 7.21, 95% CI: 2.69, 11.72 compared to Angle), year of publication (β = 0.98, 95% CI: 0.28, 1.67 for each additional year), region of authorship (Europe: β = 5.19, 95% CI: 1.30, 9.09 compared to Asia/other), statistical significance (significant: β = 3.10, 95% CI: 0.11, 6.10 compared to non-significant) and methodologist involvement (involvement: β = 5.60, 95% CI: 1.66, 9.54 compared to non-involvement) were all significant predictors of improved modified CONSORT scores in the multivariable model. Additionally, median overall Jadad score was 2 (IQR = 2) across journals, with JO (median = 3, IQR = 1) and AJODO (median = 3, IQR = 2) presenting the highest score values. CONCLUSION The reporting quality of RCTs published in leading orthodontic journals is considered suboptimal in various CONSORT areas. This may have a bearing in trial result interpretation and use in clinical decision making and evidence- based orthodontic treatment interventions.

Active implementation strategy of CONSORT adherence by a dental specialty journal improved randomized clinical trial reporting.

OBJECTIVE To describe a novel CONsolidated Standards of Reporting Trials (CONSORT) adherence strategy implemented by the American Journal of Orthodontics and Dentofacial Orthopedics (AJO-DO) and to report its impact on the completeness of reporting of published trials. STUDY DESIGN AND SETTING The AJO-DO CONSORT adherence strategy, initiated in June 2011, involves active assessment of randomized clinical trial (RCT) reporting during the editorial process. The completeness of reporting CONSORT items was compared between trials submitted and published during the implementation period (July 2011 to September 2013) and trials published between August 2007 and July 2009. RESULTS Of the 42 RCTs submitted (July 2011 to September 2013), 23 were considered for publication and assessed for completeness of reporting, seven of which were eventually published. For all published RCTs between 2007 and 2009 (n = 20), completeness of reporting by CONSORT item ranged from 0% to 100% (Median = 40%, interquartile range = 60%). All published trials in 2011-2013, reported 33 of 37 CONSORT (sub) items. Four CONSORT 2010 checklist items remained problematic even after implementation of the adherence strategy: changes to methods (3b), changes to outcomes (6b) after the trial commenced, interim analysis (7b), and trial stopping (14b), which are typically only reported when applicable. CONCLUSION Trials published following implementation of the AJO-DO CONSORT adherence strategy completely reported more CONSORT items than those published or submitted previously.

Assessing the reporting quality in abstracts of randomized controlled trials in leading journals of oral implantology.

AIM Abstracts of randomized clinical trials are extremely important as trial appraisal is often based on the information included here. The objective of this study was to assess the quality of the reporting of RCT abstracts in journals of Oral Implantology. MATERIAL AND METHODS Six leading Implantology journals were screened for RCTs between years 2008 and 2012. A 21-item modified CONSORT for abstracts checklist was used to examine the completeness of abstract reporting. Descriptive statistics and linear regression modeling were employed for data analysis. RESULTS One hundred and sixty three RCT abstracts were included in this study. The majority of the RCTs were published in the Clinical Oral Implants Research (42.9%). The mean overall reporting quality score was 58.6% (95% CI: 57.6-59.7). The highest score was noted in the European Journal of Oral Implantology (63.8%; 95% CI: 61.8-65.8). Multivariate analysis demonstrated that abstract quality score was related to publication journal and number of research centers involved. Most abstracts adequately reported interventions (89.0%), objectives (77.9%) and conclusions (74.8%) while failed to report randomization procedures, allocation concealment, effect estimate, confidence intervals, and funding. Registration of RCTs was not reported in any of the abstracts. CONCLUSIONS The reporting quality in abstracts of RCTs published in Oral Implantology journals needs to be improved. Editors and authors should be encouraged to endorse the CONSORT for abstracts guidelines in order to achieve optimal quality in abstract reporting.

The application of medical informatics to the veterinary management programs at companion animal practices in Alberta, Canada: a case study.

Companion animals closely share their domestic environment with people and have the potential to, act as sources of zoonotic diseases. They also have the potential to be sentinels of infectious and noninfectious, diseases. With the exception of rabies, there has been minimal ongoing surveillance of, companion animals in Canada. We developed customized data extraction software, the University of, Calgary Data Extraction Program (UCDEP), to automatically extract and warehouse the electronic, medical records (EMR) from participating private veterinary practices to make them available for, disease surveillance and knowledge creation for evidence-based practice. It was not possible to build, generic data extraction software; the UCDEP required customization to meet the specific software, capabilities of the veterinary practices. The UCDEP, tailored to the participating veterinary practices', management software, was capable of extracting data from the EMR with greater than 99%, completeness and accuracy. The experiences of the people developing and using the UCDEP and the, quality of the extracted data were evaluated. The electronic medical record data stored in the data, warehouse may be a valuable resource for surveillance and evidence-based medical research.