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Search Results: 1 - 10 of 383921 matches for " Karin C. L?drup Carlsen "
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A Genome-Wide Association Study in Chronic Obstructive Pulmonary Disease (COPD): Identification of Two Major Susceptibility Loci
Sreekumar G. Pillai ,Dongliang Ge equal contributor,Guohua Zhu equal contributor,Xiangyang Kong equal contributor,Kevin V. Shianna,Anna C. Need,Sheng Feng,Craig P. Hersh,Per Bakke,Amund Gulsvik,Andreas Ruppert,Karin C. Ldrup Carlsen,Allen Roses,Wayne Anderson,ICGN Investigators,Stephen I. Rennard,David A. Lomas,Edwin K. Silverman,David B. Goldstein
PLOS Genetics , 2009, DOI: 10.1371/journal.pgen.1000421
Abstract: There is considerable variability in the susceptibility of smokers to develop chronic obstructive pulmonary disease (COPD). The only known genetic risk factor is severe deficiency of α1-antitrypsin, which is present in 1–2% of individuals with COPD. We conducted a genome-wide association study (GWAS) in a homogenous case-control cohort from Bergen, Norway (823 COPD cases and 810 smoking controls) and evaluated the top 100 single nucleotide polymorphisms (SNPs) in the family-based International COPD Genetics Network (ICGN; 1891 Caucasian individuals from 606 pedigrees) study. The polymorphisms that showed replication were further evaluated in 389 subjects from the US National Emphysema Treatment Trial (NETT) and 472 controls from the Normative Aging Study (NAS) and then in a fourth cohort of 949 individuals from 127 extended pedigrees from the Boston Early-Onset COPD population. Logistic regression models with adjustments of covariates were used to analyze the case-control populations. Family-based association analyses were conducted for a diagnosis of COPD and lung function in the family populations. Two SNPs at the α-nicotinic acetylcholine receptor (CHRNA 3/5) locus were identified in the genome-wide association study. They showed unambiguous replication in the ICGN family-based analysis and in the NETT case-control analysis with combined p-values of 1.48×10?10, (rs8034191) and 5.74×10?10 (rs1051730). Furthermore, these SNPs were significantly associated with lung function in both the ICGN and Boston Early-Onset COPD populations. The C allele of the rs8034191 SNP was estimated to have a population attributable risk for COPD of 12.2%. The association of hedgehog interacting protein (HHIP) locus on chromosome 4 was also consistently replicated, but did not reach genome-wide significance levels. Genome-wide significant association of the HHIP locus with lung function was identified in the Framingham Heart study (Wilk et al., companion article in this issue of PLoS Genetics; doi:10.1371/journal.pgen.1000429). The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD. CHRNA3/5 is the same locus that has been implicated in the risk of lung cancer.
Does Pet Ownership in Infancy Lead to Asthma or Allergy at School Age? Pooled Analysis of Individual Participant Data from 11 European Birth Cohorts
Karin C. Ldrup Carlsen, Stephanie Roll, Kai-H?kon Carlsen, Petter Mowinckel, Alet H. Wijga, Bert Brunekreef, Maties Torrent, Graham Roberts, S. Hasan Arshad, Inger Kull, Ursula Kr?mer, Andrea von Berg, Esben Eller, Arne H?st, Claudia Kuehni, Ben Spycher, Jordi Sunyer, Chih-Mei Chen, Andreas Reich, Anna Asarnoj, Carmen Puig, Olf Herbarth, Jestinah M. Mahachie John, Kristel Van Steen, Stefan N. Willich, Ulrich Wahn, Susanne Lau, Thomas Keil, GA 2 LEN WP 1.5 ‘Birth Cohorts’ working group
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043214
Abstract: Objective To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years. Design Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. Exposure definition Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. Outcome definition Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age. Data synthesis Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models. Results We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I2 = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I2 = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I2 = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens. Conclusions Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.
Long-Term Gynecological Outcomes in Women with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency
TH Johannsen, C PL Ripa, E Carlsen, J Starup, O H Nielsen, M Schwartz, K T Drzewiecki, E L Mortensen, K M Main
International Journal of Pediatric Endocrinology , 2010, DOI: 10.1155/2010/784297
Abstract: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disorder characterized by impaired or total loss of activity in the enzyme required for cortisol and aldosterone production, resulting in highly increased adrenal androgen synthesis [1]. Depending on the severity of the underlying defect in CYP21, female CAH patients show varying degrees of genital virilisation. Ambiguous genitalia in the newborn, severe clitoromegaly, and vaginal stenosis may require many diagnostic and surgical procedures, not only initially, but also repetitively during adolescence. Despite an increasing focus on optimal treatment of CAH patients, our knowledge of long-term outcomes of this condition remains incomplete. Thus, the aim of the present study was to evaluate gynecological and reproductive outcomes in a group of women diagnosed with CAH due to 21-hydroxylase deficiency in childhood or adolescence.This study was part of a follow-up study of adult female patients diagnosed with disorders of sex development (DSD) at the University Hospital of Copenhagen (Rigshospitalet) from 1953–2003. Participation rate was 81%. In total, 33 CAH patients with genetically verified CYP21 deficiency were included (30 yrs, 19–52). As previously reported [2, 3], patients with CYP21 deficiency were divided according to the clinical data and the predicted severity of the mutation [4] into salt-wasters (SW, = 21), simple-virilizers (SV, = 6), and late-onset (LO, = 5) CAH. One patient was first diagnosed in adolescence and was in the present study included in the group of patients with late-onset CAH.Diagnosis of CAH patients occurred at a median age of 0 yrs (0–16 yrs). At birth, seven patients with salt-wasting CAH were assigned male gender, but with a reassignment to females during the first months of life, while ten salt-wasters and two simple-virilizers with ambiguous genitalia at birth were assigned female gender. Data on virilisation at birth was missing in two patien
The association between renal function and structural parameters: a pig study
Anders B Ldrup, Kristian Karstoft, Thomas H Dissing, Jens R Nyengaard, Michael Pedersen
BMC Nephrology , 2008, DOI: 10.1186/1471-2369-9-18
Abstract: Twenty-four pigs, twelve with healthy kidneys and twelve with diseased kidneys, underwent skGFR measurements. Nephrectomies were performed and structural parameters were estimated using stereological procedures. The correlation between the structural parameters and skGFR was analysed by Pearson's correlation test. The prediction of skGFR from structural parameters was analysed by a linear regression test.In general, we demonstrated a good correlation between structural parameters and skGFR. When all kidneys were evaluated together Pearson's correlation coefficient between skGFR and any stereological parameter was above 0.60 and highly significant (p < 0.001), and with r-values ranging from 0.62 regarding number of glomeruli, to 0.78 regarding cortical volume. The best correlation was found between cortical volume and skGFR. Prediction of single kidney GFR from any structural parameter showed to be quite imprecise.The observed correlations between structural parameters and renal function suggest that these parameters may potentially be useful as surrogate markers of the renal function. At present, however, precise prediction of renal function based on a single structural parameter seems hard to obtain.The pathology of chronic kidney disease usually involves structural and functional changes, often interconnected, and according to the hyperfiltration theory, as proposed by Brenner et al, a reduction in the number of glomeruli (N(glom)) leads to hemodynamic changes associated with glomerular hypertension, hyperfiltration and proteinuria [1].The relationship between renal structural and functional parameters is still not fully understood. Widjaja et al concluded that three-dimensional structural parameters such as total kidney volume (V(total)) correlates better to the kidney function than two-dimensional structural parameters [2]. Volume of cortex (V(cor)) has been shown to diminish over time in patients with chronically injured kidneys [3]. N(glom) has been shown to d
The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide
Monica H Carlsen, Bente L Halvorsen, Kari Holte, Siv K B?hn, Steinar Dragland, Laura Sampson, Carol Willey, Haruki Senoo, Yuko Umezono, Chiho Sanada, Ingrid Barikmo, Nega Berhe, Walter C Willett, Katherine M Phillips, David R Jacobs, Rune Blomhoff
Nutrition Journal , 2010, DOI: 10.1186/1475-2891-9-3
Abstract: We procured samples from countries worldwide and assayed the samples for their total antioxidant content using a modified version of the FRAP assay. Results and sample information (such as country of origin, product and/or brand name) were registered for each individual food sample and constitute the Antioxidant Food Table.The results demonstrate that there are several thousand-fold differences in antioxidant content of foods. Spices, herbs and supplements include the most antioxidant rich products in our study, some exceptionally high. Berries, fruits, nuts, chocolate, vegetables and products thereof constitute common foods and beverages with high antioxidant values.This database is to our best knowledge the most comprehensive Antioxidant Food Database published and it shows that plant-based foods introduce significantly more antioxidants into human diet than non-plant foods. Because of the large variations observed between otherwise comparable food samples the study emphasizes the importance of using a comprehensive database combined with a detailed system for food registration in clinical and epidemiological studies. The present antioxidant database is therefore an essential research tool to further elucidate the potential health effects of phytochemical antioxidants in diet.It is widely accepted that a plant-based diet with high intake of fruits, vegetables, and other nutrient-rich plant foods may reduce the risk of oxidative stress-related diseases [1-6]. Understanding the complex role of diet in such chronic diseases is challenging since a typical diet provides more than 25,000 bioactive food constituents [6], many of which may modify a multitude of processes that are related to these diseases. Because of the complexity of this relationship, it is likely that a comprehensive understanding of the role of these bioactive food components is needed to assess the role of dietary plants in human health and disease development. We suggest that both their numerous ind
Healthy Volunteers Can Be Phenotyped Using Cutaneous Sensitization Pain Models
Mads U. Werner, Karin L. Petersen, Michael C. Rowbotham, J?rgen B. Dahl
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0062733
Abstract: Background Human experimental pain models leading to development of secondary hyperalgesia are used to estimate efficacy of analgesics and antihyperalgesics. The ability to develop an area of secondary hyperalgesia varies substantially between subjects, but little is known about the agreement following repeated measurements. The aim of this study was to determine if the areas of secondary hyperalgesia were consistently robust to be useful for phenotyping subjects, based on their pattern of sensitization by the heat pain models. Methods We performed post-hoc analyses of 10 completed healthy volunteer studies (n = 342 [409 repeated measurements]). Three different models were used to induce secondary hyperalgesia to monofilament stimulation: the heat/capsaicin sensitization (H/C), the brief thermal sensitization (BTS), and the burn injury (BI) models. Three studies included both the H/C and BTS models. Results Within-subject compared to between-subject variability was low, and there was substantial strength of agreement between repeated induction-sessions in most studies. The intraclass correlation coefficient (ICC) improved little with repeated testing beyond two sessions. There was good agreement in categorizing subjects into ‘small area’ (1st quartile [<25%]) and ‘large area’ (4th quartile [>75%]) responders: 56–76% of subjects consistently fell into same ‘small-area’ or ‘large-area’ category on two consecutive study days. There was moderate to substantial agreement between the areas of secondary hyperalgesia induced on the same day using the H/C (forearm) and BTS (thigh) models. Conclusion Secondary hyperalgesia induced by experimental heat pain models seem a consistent measure of sensitization in pharmacodynamic and physiological research. The analysis indicates that healthy volunteers can be phenotyped based on their pattern of sensitization by the heat [and heat plus capsaicin] pain models.
Diagnosis of Asthma in Primary Health Care: A Pilot Study
Karin C. Ringsberg,Paula Bj?rneman,Ronny Larsson,Elisabeth Wallstr?m,Olle L?whagen
Journal of Allergy , 2014, DOI: 10.1155/2014/898965
Abstract: Some patients with an asthma diagnosis have a poor controlled asthma. One explanation may be an incorrect diagnosis. Aim. The aim of the study was to diagnose and classify patients with non-infectious lower respiratory tract problems in primary health care using internationally applied diagnostic criteria and diagnostic tests. Patients and Methods. New adult patients visiting a primary health care centre due to lower airway problems were included. The diagnostic tests included FEV1, FVC, PEF, two questionnaires, methacholine test, and skin prick test. Results. The patients ( ) could be divided into four groups: asthma (28%), asthma-like disorder (44%), idiopathic cough (12%), and a nonreversible bronchial obstructive group (16%). The asthma and asthma-like groups showed similar patterns of airway symptoms and trigger factors, not significantly separated by a special questionnaire. Phlegm, heavy breathing, chest pressure/pain, cough, and wheezing were the most common symptoms. Physical exercise and scents were the dominating trigger factors. Conclusions. Nonobstructive asthma-like symptoms seem to be as common as bronchial asthma in primary health care. Due to the similarities in symptoms and trigger factors the study supports the hypothesis that asthma and nonobstructive asthma-like disorders are integrated in the same “asthma syndrome,” including different mechanisms, not only bronchial obstruction. 1. Introduction Bronchial asthma is a common disease worldwide and good treatment could often be offered [1]. Its prevalence in the adult population in Sweden is up to 10% [2], being the highest in the north part and in younger people. The diagnosis is based on the presence of episodic breathing troubles and variable and reversible airway obstruction [1, 3]. Most cases are not difficult to diagnose and treat; however, some patients respond poorly to asthma treatment despite ongoing asthma-like symptoms. In those cases, other diagnoses must be considered [4–15]. Disorders with asthma-like symptoms mentioned in the literature are dysfunctional breathing [11, 16–18], vocal cord dysfunction [19], pseudoasthma [20], cough variant asthma [8], multiple chemical sensitivity [21], and airway sensory hyperreactivity (SHR) [22]. In GINA, the international guidelines for asthma diagnostics and treatment [1], two disorders with asthma-like symptoms are mentioned, vocal cord dysfunction (VC) [19] and hyperventilation syndrome (HVS) [7]. As the above conditions are presented under different names, it is not possible to know the prevalence. However, Marklund et al. found
Constraining the X-ray and Cosmic Ray Ionization Chemistry of the TW Hya Protoplanetary Disk: Evidence for a Sub-interstellar Cosmic Ray Rate
L. Ilsedore Cleeves,Edwin A. Bergin,Chunhua Qi,Fred C. Adams,Karin I. Oberg
Physics , 2014, DOI: 10.1088/0004-637X/799/2/204
Abstract: We present an observational and theoretical study of the primary ionizing agents (cosmic rays and X-rays) in the TW Hya protoplanetary disk. We use a set of resolved and unresolved observations of molecular ions and other molecular species, encompassing eleven lines total, in concert with a grid of disk chemistry models. The molecular ion constraints comprise new data from the Submillimeter Array on HCO$^+$, acquired at unprecedented spatial resolution, and data from the literature, including ALMA observations of N$_2$H$^+$. We vary the model incident CR flux and stellar X-ray spectra and find that TW Hya's HCO$^+$ and N$_2$H$^+$ emission are best fit by a moderately hard X-ray spectra, as would be expected during the "flaring" state of the star, and a low CR ionization rate, $\zeta_{\rm CR}\lesssim10^{-19}$ s$^{-1}$. This low CR rate is the first indication of the presence of CR exclusion by winds and/or magnetic fields in an actively accreting T Tauri disk system. With this new constraint, our best fit ionization structure predicts a low turbulence "dead-zone" extending from the inner edge of the disk out to $50-65$ AU. This region coincides with an observed concentration of millimeter grains, and we propose that the inner region of TW Hya is a dust (and possibly planet) growth factory as predicted by previous theoretical work.
Haloquadratum walsbyi : Limited Diversity in a Global Pond
Mike L. Dyall-Smith, Friedhelm Pfeiffer, Kathrin Klee, Peter Palm, Karin Gross, Stephan C. Schuster, Markus Rampp, Dieter Oesterhelt
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0020968
Abstract: Background Haloquadratum walsbyi commonly dominates the microbial flora of hypersaline waters. Its cells are extremely fragile squares requiring >14%(w/v) salt for growth, properties that should limit its dispersal and promote geographical isolation and divergence. To assess this, the genome sequences of two isolates recovered from sites at near maximum distance on Earth, were compared. Principal Findings Both chromosomes are 3.1 MB in size, and 84% of each sequence was highly similar to the other (98.6% identity), comprising the core sequence. ORFs of this shared sequence were completely synteneic (conserved in genomic orientation and order), without inversion or rearrangement. Strain-specific insertions/deletions could be precisely mapped, often allowing the genetic events to be inferred. Many inferred deletions were associated with short direct repeats (4–20 bp). Deletion-coupled insertions are frequent, producing different sequences at identical positions. In cases where the inserted and deleted sequences are homologous, this leads to variant genes in a common synteneic background (as already described by others). Cas/CRISPR systems are present in C23T but have been lost in HBSQ001 except for a few spacer remnants. Numerous types of mobile genetic elements occur in both strains, most of which appear to be active, and with some specifically targetting others. Strain C23T carries two ~6 kb plasmids that show similarity to halovirus His1 and to sequences nearby halovirus/plasmid gene clusters commonly found in haloarchaea. Conclusions Deletion-coupled insertions show that Hqr. walsbyi evolves by uptake and precise integration of foreign DNA, probably originating from close relatives. Change is also driven by mobile genetic elements but these do not by themselves explain the atypically low gene coding density found in this species. The remarkable genome conservation despite the presence of active systems for genome rearrangement implies both an efficient global dispersal system, and a high selective fitness for this species.
Improving antibiotic prescribing for adults with community acquired pneumonia: Does a computerised decision support system achieve more than academic detailing alone? – a time series analysis
Kirsty L Buising, Karin A Thursky, James F Black, Lachlan MacGregor, Alan C Street, Marcus P Kennedy, Graham V Brown
BMC Medical Informatics and Decision Making , 2008, DOI: 10.1186/1472-6947-8-35
Abstract: The management of all patients presenting to the emergency department over three successive time periods was evaluated; the baseline, academic detailing and CDSS periods. The rate of empiric antibiotic prescribing that was concordant with recommendations was studied over time comparing pre and post periods and using an interrupted time series analysis.The odds ratio for concordant therapy in the academic detailing period, after adjustment for age, illness severity and suspicion of aspiration, compared with the baseline period was OR = 2.79 [1.88, 4.14], p < 0.01, and for the computerised decision support period compared to the academic detailing period was OR = 1.99 [1.07, 3.69], p = 0.02. During the first months of the computerised decision support period an improvement in the appropriateness of antibiotic prescribing was demonstrated, which was greater than that expected to have occurred with time and academic detailing alone, based on predictions from a binary logistic model.Deployment of a computerised decision support system was associated with an early improvement in antibiotic prescribing practices which was greater than the changes seen with academic detailing. The sustainability of this intervention requires further evaluation.With the rapidly expanding body of medical knowledge, clinicians need access to appropriate, relevant information to guide their clinical decision making. For many conditions, clinical experts have used available evidence and experience to generate guidelines that endeavour to assist clinicians, and improve patient outcomes. A major problem, however, has been finding the best strategies to implement these guidelines in a busy hospital environment. [1-3] Group lectures, one to one academic detailing, laminated cards and advertising material such as posters have all been tried with variable success. [4-7] With the increasing role played by computers as a source of information in the hospital setting, computerised decision support may pr
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