| 26. |
- Kraus, V. B., et al.
(författare)
-
Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis
- 2011
-
Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19:5, s. 515-542
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Osteoarthritis (OA) is a chronic and slowly progressive disease for which biomarkers may be able to provide a more rapid indication of therapeutic responses to therapy than is currently available; this could accelerate and facilitate OA drug discovery and development programs. The goal of this document is to provide a summary and guide to the application of in vitro (biochemical and other soluble) biomarkers in the development of drugs for OA and to outline and stimulate a research agenda that will further this goal. Methods: The Biomarkers Working Group representing experts in the field of OA biomarker research from both academia and industry developed this consensus document between 2007 and 2009 at the behest of the Osteoarthritis Research Society International Federal Drug Administration initiative (OARSI FDA initiative). Results: This document summarizes definitions and classification systems for biomarkers, the current outcome measures used in OA clinical trials, applications and potential utility of biomarkers for development of OA therapeutics, the current state of qualification of OA-related biomarkers, pathways for biomarker qualification, critical needs to advance the use of biomarkers for drug development, recommendations regarding practices and clinical trials, and a research agenda to advance the science of OA-related biomarkers. Conclusions: Although many OA-related biomarkers are currently available they exist in various states of qualification and validation. The biomarkers that are likely to have the earliest beneficial impact on clinical trials fall into two general categories, those that will allow targeting of subjects most likely to either respond and/or progress (prognostic value) within a reasonable and manageable time frame for a clinical study (for instance within 1-2 years for an OA trial), and those that provide early feedback for preclinical decision-making and for trial organizers that a drug is having the desired biochemical effect. As in vitro biomarkers are increasingly investigated in the context of specific drug treatments, advances in the field can be expected that will lead to rapid expansion of the list of available biomarkers with increasing understanding of the molecular processes that they represent. (C) 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
|
|
| 27. |
- Lundgren, Markus, et al.
(författare)
-
Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
-
Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
|
|
| 28. |
- Moshontz, Hannah, et al.
(författare)
-
The Psychological Science Accelerator: Advancing Psychology Through a Distributed Collaborative Network
- 2018
-
Ingår i: Advances in Methods and Practices in Psychological Science. - : SAGE Publications. - 2515-2459 .- 2515-2467. ; 1:4, s. 501-515
-
Tidskriftsartikel (refereegranskat)abstract
- Concerns about the veracity of psychological research have been growing. Many findings in psychological science are based on studies with insufficient statistical power and nonrepresentative samples, or may otherwise be limited to specific, ungeneralizable settings or populations. Crowdsourced research, a type of large-scale collaboration in which one or more research projects are conducted across multiple lab sites, offers a pragmatic solution to these and other current methodological challenges. The Psychological Science Accelerator (PSA) is a distributed network of laboratories designed to enable and support crowdsourced research projects. These projects can focus on novel research questions or replicate prior research in large, diverse samples. The PSA’s mission is to accelerate the accumulation of reliable and generalizable evidence in psychological science. Here, we describe the background, structure, principles, procedures, benefits, and challenges of the PSA. In contrast to other crowdsourced research networks, the PSA is ongoing (as opposed to time limited), efficient (in that structures and principles are reused for different projects), decentralized, diverse (in both subjects and researchers), and inclusive (of proposals, contributions, and other relevant input from anyone inside or outside the network). The PSA and other approaches to crowdsourced psychological science will advance understanding of mental processes and behaviors by enabling rigorous research and systematic examination of its generalizability.
|
|
| 29. |
- Richardson, R. T., et al.
(författare)
-
A reference cytochrome c oxidase subunit I database curated for hierarchical classification of arthropod metabarcoding data
- 2018
-
Ingår i: Peerj. - : PeerJ. - 2167-8359. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Metabarcoding is a popular application which warrants continued methods optimization. To maximize barcoding inferences, hierarchy-based sequence classification methods are increasingly common. We present methods for the construction and curation of a database designed for hierarchical classification of a 157 bp barcoding region of the arthropod cytochrome c oxidase subunit I (COI) locus. We produced a comprehensive arthropod COI amplicon dataset including annotated arthropod COI sequences and COI sequences extracted from arthropod whole mitochondrion genomes, the latter of which provided the only source of representation for Zoraptera, Callipodida and Holothyrida. The database contains extracted sequences of the target amplicon from all major arthropod clades, including all insect orders, all arthropod classes and Onychophora, Tardigrada and Mollusca outgroups. During curation, we extracted the COI region of interest from approximately 81 percent of the input sequences, corresponding to 73 percent of the genus-level diversity found in the input data. Further, our analysis revealed a high degree of sequence redundancy within the NCBI nucleotide database, with a mean of approximately 11 sequence entries per species in the input data. The curated, low-redundancy database is included in the Metaxa2 sequence classification software (http://microbiolognse/software/metaxa2/). Using this database with the Metaxa2 classifier, we performed a cross-validation analysis to characterize the relationship between the Metaxa2 reliability score, an estimate of classification confidence, and classification error probability. We used this analysis to select a reliability score threshold which minimized error. We then estimated classification sensitivity, false discovery rate and overclassification, the propensity to classify sequences from taxa not represented in the reference database. Our work will help researchers design and evaluate classification databases and conduct metabarcoding on arthropods and alternate taxa.
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
- Chioza, Barry A., et al.
(författare)
-
Genome wide high density SNP-based linkage analysis of childhood absence epilepsy identifies a susceptibility locus on chromosome 3p23-p14
- 2009
-
Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211 .- 1872-6844. ; 87:2-3, s. 247-255
-
Tidskriftsartikel (refereegranskat)abstract
- Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy (IGE) characterised by typical absence seizures manifested by transitory loss of awareness with 2.5-4 Hz spike-wave complexes on ictal EEG. A genetic component to the aetiology is well recognised but the mechanism of inheritance and the genes involved are yet to be fully established. A genome wide single nucleotide polymorphism (SNP)-based high density linkage scan was carried out using 41 nuclear pedigrees with at least two affected members. Multipoint parametric and non-parametric linkage analyses were performed using MERLIN 1.1.1 and a susceptibility locus was identified on chromosome 3p23-p14 (Z(mean)=3.9, p<0.0001; HLOD=3.3, alpha=0.7). The linked region harbours the functional candidate genes TRAK1 and CACNA2D2. Fine-mapping using a tagSNP approach demonstrated disease association with variants in TRAK1.
|
|
| 37. |
- Clayton, Aled, et al.
(författare)
-
Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017
- 2018
-
Ingår i: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 7
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. This report summarises the presentations and activities of the ISEV Workshop on extracellular vesicle biomarkers held in Birmingham, UK during December 2017. Among the key messages was broad agreement about the importance of biospecimen science. Much greater attention needs to be paid towards the provenance of collected samples. The workshop also highlighted clear gaps in our knowledge about pre-analytical factors that alter extracellular vesicles (EVs). The future utility of certified standards for credentialing of instruments and software, to analyse EV and for tracking the influence of isolation steps on the structure and content of EVs were also discussed. Several example studies were presented, demonstrating the potential utility for EVs in disease diagnosis, prognosis, longitudinal serial testing and stratification of patients. The conclusion of the workshop was that more effort focused on pre-analytical issues and benchmarking of isolation methods is needed to strengthen collaborations and advance more effective biomarkers.
|
|
| 38. |
|
|
| 39. |
- Cordoza, Makayla, et al.
(författare)
-
Impact of nurses taking daily work breaks in a hospital garden on Burnout
- 2018
-
Ingår i: American Journal of Critical Care. - : AACN Publishing. - 1062-3264 .- 1937-710X. ; 27:6, s. 508-512
-
Tidskriftsartikel (refereegranskat)abstract
- Background Nurses working in hospital environments are at risk for burnout. Exposure to nature has psychological benefits, but the effect of hospital gardens on nurse burnout is less understood. Objective To compare the effect on nurse burnout of taking daily work breaks in a hospital-integrated garden with the effect of indoor-only breaks. Methods A prospective crossover trial was conducted of nurses assigned to either 6 weeks of a work break in an outdoor hospital garden or 6 weeks of indoor-only breaks. After a 1-week washout period, break assignments were switched for a subsequent 6 weeks. The Maslach Burnout Inventory was administered at the beginning and end of each 6-week period, and a Present Functioning Visual Analogue Scale was completed at the start and end of each break to capture immediate psychological symptoms. Change scores were analyzed by using generalized estimating equations. Results For 29 nurses, for garden compared with indoor breaks, significant improvement was apparent in scores on the Maslach Burnout Inventory subscales for emotional exhaustion (4.5 vs -0.2; P < .001) and depersonalization (1.8 vs 0.0; P = .02) but not for personal accomplishment (-0.6 vs -0.0; P = .55). Compared with indoor breaks, total symptom scores on the Present Functioning Visual Analog Scale improved significantly when nurses took a break in the garden (garden vs indoor breaks, 4.0 vs 2.4; P = .04). Conclusions Taking daily work breaks in an outdoor garden may be beneficial in mitigating burnout for nurses working in hospital environments.
|
|
| 40. |
- Gardiner, K., et al.
(författare)
-
Of Messages and Meaning.
- 1997
-
Ingår i: Trends Genet.. ; 13, s. 92-
-
Tidskriftsartikel (refereegranskat)
|
|
| 41. |
|
|
| 42. |
- Gardiner, T., et al.
(författare)
-
Trend analysis of greenhouse gases over Europe measured by a network of ground-based remote FTIR instruments
- 2008
-
Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 8:22, s. 6719-6727
-
Tidskriftsartikel (refereegranskat)abstract
- This paper describes the statistical analysis of annual trends in long term datasets of greenhouse gas measurements taken over ten or more years. The analysis technique employs a bootstrap resampling method to determine both the long-term and intra-annual variability of the datasets, together with the uncertainties on the trend values. The method has been applied to data from a European network of ground-based solar FTIR instruments to determine the trends in the tropospheric, stratospheric and total columns of ozone, nitrous oxide, carbon monoxide, methane, ethane and HCFC-22. The suitability of the method has been demonstrated through statistical validation of the technique, and comparison with ground-based in-situ measurements and 3-D atmospheric models.
|
|
| 43. |
- Hudson, P L, et al.
(författare)
-
Strategies and checklist for designing and conducting palliative care research with family carers : EAPC international expert elicitation study
- 2023
-
Ingår i: Palliative Medicine. - : Sage Publications. - 0269-2163 .- 1477-030X. ; 37:1, s. 163-173
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Palliative care services seek to improve the wellbeing of family carers of people living with serious and life-limiting illness. To help achieve this goal, systematic reviews have recommended priority areas for family carer research and the need to improve the quality of study design. Policy makers have also advocated for enhanced family carer support. However, there are specific methodological considerations and challenges in designing and conducting carer research conducted during the course of the serious illness trajectory and in bereavement.AIM: To develop strategies to improve the design and conduct of research with family carers.DESIGN: Expert elicitation study using an adapted version of the 'Identify, Discuss, Estimate and Aggregate' elicitation protocol, supplemented with strategies from peer-reviewed literature.SETTING/PARTICIPANTS: Nine members of the management committee of the European Association for Palliative Care's Reference group on family carer research, comprising international senior research academics in family caregiving.RESULTS: A compilation of recommended strategies and checklist was created to: (a) help researchers plan research involving family carers focussing on: preparation, conduct and dissemination and (b) assist ethics committees and funding bodies to evaluate proposals.CONCLUSIONS: The strategies and checklist for conducting research with family carers may enhance methodologically rigorous research. Consequently, researchers, practitioners and policy makers will not only gain a more comprehensive understanding of the unmet needs of family carers but also promote the development of empirically sound interventions.
|
|
| 44. |
|
|
| 45. |
- Kovacevic, A., et al.
(författare)
-
Fetal aortic valvuloplasty : investigating institutional bias in surgical decision-making
- 2014
-
Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 44:5, s. 538-544
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives Fetal aortic valvuloplasty may prevent the progression of aortic stenosis to hypoplastic left heart syndrome and allow biventricular rather than univentricular postnatal treatment. This study aimed to investigate whether blinded simulation of a multidisciplinary team approach aids interpretation of multicenter data to uncover institutional bias in postnatal decision-making following fetal cardiac intervention for aortic stenosis. Methods The study included 109 cases of prenatally diagnosed aortic stenosis from 13 European countries, of which 32 had undergone fetal cardiac intervention. The multidisciplinary team, blinded to fetal cardiac intervention, institutional location and postnatal treatment, retrospectively assigned a surgical pathway (biventricular or univentricular) based on a review of recorded postnatal imaging and clinical characteristics. The team's decisions were the numerical consensus of silent voting, with case review when a decision was split. Funnel plots showing concordance between the multidisciplinary team and the local team's surgical choice (first pathway) and with outcome (final pathway) were created. Results In 105 cases the multidisciplinary team reached a consensus decision regarding the surgical pathway, with no decision in four cases because the available imaging records were inadequate. Blinded multidisciplinary team consensus for the first pathway matched the decision of the surgical center in 93/105 (89%) cases, with no difference in agreement between those that had undergone successful fetal cardiac intervention (n= 32) and no (n= 74) or unsuccessful (n= 3) valvuloplasty (no fetal cardiac intervention) (kappa = 0.73 (95% CI, 0.38-1.00) vs 0.74 (95% CI, 0.51-0.96)). However, funnel plots comparing multidisciplinary team individual decisions with those of the local teams displayed more discordance (meaning biventricular-univentricular conversion) for the final surgical pathway following fetal cardiac intervention than they did for cases without such intervention (36/74 vs 34/130; P = 0.002), and identified one outlying center. Conclusions The use of a blinded multidisciplinary team to simulate decision-making and presentation of data in funnel plots may assist in the interpretation of data submitted to multicenter studies and permit the identification of outliers for further investigation. In the case of aortic stenosis, a high level of agreement was observed between the multidisciplinary team and the surgical centers, but one outlying center was identified.
|
|
| 46. |
|
|
| 47. |
- Ma, Li-Jun, et al.
(författare)
-
Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium.
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 464:7287, s. 367-73
-
Tidskriftsartikel (refereegranskat)abstract
- Fusarium species are among the most important phytopathogenic and toxigenic fungi. To understand the molecular underpinnings of pathogenicity in the genus Fusarium, we compared the genomes of three phenotypically diverse species: Fusarium graminearum, Fusarium verticillioides and Fusarium oxysporum f. sp. lycopersici. Our analysis revealed lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes and account for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity, indicative of horizontal acquisition. Experimentally, we demonstrate the transfer of two LS chromosomes between strains of F. oxysporum, converting a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in F. oxysporum. These findings put the evolution of fungal pathogenicity into a new perspective.
|
|
| 48. |
|
|
| 49. |
- Newton, Robert U, et al.
(författare)
-
Exercise Mode Specificity for Preserving Spine and Hip Bone Mineral Density in Prostate Cancer Patients.
- 2019
-
Ingår i: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 51:4, s. 607-614
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) is associated with an array of adverse effects, including reduced bone mineral density (BMD) predisposing patients to increased fracture risk. Our purpose was to examine the effects of targeted exercise modes on BMD in men with PCa undergoing ADT.METHODS: Between 2009 and 2012, 154 PCa patients 43-90 yr old on ADT were randomized to exercise targeting the musculoskeletal system (impact loading + resistance training [ImpRes], n = 57) supervised for 12 months, cardiovascular and muscular systems (aerobic + resistance training, n = 50) supervised for 6 months followed by a 6-month home-based program, or delayed aerobic exercise (DelAer, n = 47) received exercise information for 6 months followed by 6 months of supervised aerobic exercise (stationary cycling). End points were lumbar spine, hip and whole-body BMD measured by dual-energy x-ray absorptiometry with secondary end points of lean and fat mass, appendicular skeletal muscle mass, and neuromuscular strength. ANOVA was used to compare the exercise groups with DelAer at 6 and 12 months.RESULTS: There was a between-group difference in BMD for ImpRes and DelAer at the spine (6 months, P = 0.039; 12 months, P = 0.035) and femoral neck (6 months, P = 0.050), with decline attenuated in ImpRes (~-1.0% vs ~-2.0%). Compared with DelAer, ImpRes increased appendicular skeletal muscle at 6 months (0.3 kg, P = 0.045) and improved muscle strength at 6 and 12 months (P ≤ 0.012) by 9%-34%. A limitation was inclusion of well-functioning patients.CONCLUSION: Combined impact loading and resistance exercise attenuates bone loss at the spine and enhances overall musculoskeletal function in PCa patients undergoing ADT.
|
|
| 50. |
|
|
