| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 5. |
- Villa, Luisa L., et al.
(författare)
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Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions
- 2007
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 356:19, s. 1915-1927
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause approximately 70% of cervical cancers worldwide. A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6, 11, 16, and 18 (HPV-6/11/16/18) for the prevention of high-grade cervical lesions associated with HPV-16 and HPV-18. METHODS: In this randomized, double-blind trial, we assigned 12,167 women between the ages of 15 and 26 years to receive three doses of either HPV-6/11/16/18 vaccine or placebo, administered at day 1, month 2, and month 6. The primary analysis was performed for a per-protocol susceptible population that included 5305 women in the vaccine group and 5260 in the placebo group who had no virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the third dose (month 7). The primary composite end point was cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer related to HPV-16 or HPV-18. RESULTS: Subjects were followed for an average of 3 years after receiving the first dose of vaccine or placebo. Vaccine efficacy for the prevention of the primary composite end point was 98% (95.89% confidence interval [CI], 86 to 100) in the per-protocol susceptible population and 44% (95% CI, 26 to 58) in an intention-to-treat population of all women who had undergone randomization (those with or without previous infection). The estimated vaccine efficacy against all high-grade cervical lesions, regardless of causal HPV type, in this intention-to-treat population was 17% (95% CI, 1 to 31). CONCLUSIONS: In young women who had not been previously infected with HPV-16 or HPV-18, those in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group.
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| 6. |
- Stapleton, M. R., et al.
(författare)
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Characterisation of IsaA and SceD, two putative lytic transglycosylases of Staphylococcus aureus
- 2007
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Ingår i: J Bacteriol. - 0021-9193. ; 189
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial cell wall peptidoglycan is a dynamic structure requiring hydrolysis to allow cell wall growth and division. Staphylococcus aureus has many known and putative peptidoglycan hydrolases, including two likely lytic transglycosylases. These two proteins, IsaA and SceD, were both found to have autolytic activity. Regulatory studies showed that isaA and sceD genes are partially mutually compensatory, with the production of SceD being upregulated in an isaA mutant. The expression of sceD is also greatly upregulated by the presence of NaCl. Several regulators of isaA and sceD expression were identified. Inactivation of sceD resulted in impaired cell separation, as seen by light microscopy, and "clumping" of bacterial cultures. An isaA sceD mutant is attenuated for virulence, whilst SceD is essential for nasal colonisation in cotton rats, thus demonstrating the importance of cell wall dynamics in host-pathogen interactions.
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| 7. |
- Hannan, T. J., et al.
(författare)
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Inhibition of cyclooxygenase-2 prevents chronic and recurrent cystitis
- 2014
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 1:1, s. 46-57
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Tidskriftsartikel (refereegranskat)abstract
- The spread of multidrug-resistant microorganisms globally has created an urgent need for novel therapeuticstrategies to combat urinary tract infections (UTIs). Immunomodulatory therapy may provide benefit, as treatmentof mice with dexamethasone during acute UTI improved outcome by reducing the development of chroniccystitis, which predisposes to recurrent infection. Herewe discovered soluble biomarkers engaged inmyeloid celldevelopment and chemotaxis that were predictive of future UTI recurrence when elevated in the sera of youngwomen with UTI. Translation of these findings revealed that temperance of the neutrophil response early duringUTI, and specifically disruption of bladder epithelial transmigration of neutrophils by inhibition ofcyclooxygenase-2, protected mice against chronic and recurrent cystitis. Further, proteomics identified bladderepithelial remodeling consequent to chronic infection that enhances sensitivity to neutrophil damage. Thus, cyclooxygenase-2 expression during acute UTI is a critical molecular trigger determining disease outcome anddrugs targeting cyclooxygenase-2 could prevent recurrent UTI.
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| 10. |
- Grasselli, Giacomo, et al.
(författare)
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ESICM guidelines on acute respiratory distress syndrome : definition, phenotyping and respiratory support strategies
- 2023
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Ingår i: Intensive Care Medicine. - : Springer Nature. - 0342-4642 .- 1432-1238. ; 49, s. 727-759
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Tidskriftsartikel (refereegranskat)abstract
- The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.
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| 12. |
- Loughman, Tony, et al.
(författare)
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Analytical Validation of a Novel 6-Gene Signature for Prediction of Distant Recurrence in Estrogen Receptor-Positive, HER2-Negative, Early-Stage Breast Cancer
- 2022
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 68:6, s. 837-847
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundOncoMasTR is a recently developed multigene prognostic test for early-stage breast cancer. The test has been developed in a kit-based format for decentralized deployment in molecular pathology laboratories. The analytical performance characteristics of the OncoMasTR test are described in this study.MethodsExpression levels of 6 genes were measured by 1-step reverse transcription-quantitative PCR on RNA samples prepared from formalin-fixed, paraffin-embedded (FFPE) breast tumor specimens. Assay precision, reproducibility, input range, and interference were determined using FFPE-derived RNA samples representative of low and high prognostic risk scores. A pooled RNA sample derived from 6 FFPE breast tumor specimens was used to establish the linear range, limit of detection, and amplification efficiency of the individual gene expression assays.ResultsThe overall precision of the OncoMasTR test was high with an SD of 0.16, which represents less than 2% of the 10-unit risk score range. Test results were reproducible across 4 testing sites, with correlation coefficients of 0.94 to 0.96 for the continuous risk score and concordance of 86% to 96% in low-/high-risk sample classification. Consistent risk scores were obtained across a > 100-fold RNA input range. Individual gene expression assays were linear up to quantification cycle values of 36.0 to 36.9, with amplification efficiencies of 80% to 102%. Test results were not influenced by agents used during RNA isolation, by low levels of copurified genomic DNA, or by moderate levels of copurified adjacent nontumor tissue.ConclusionThe OncoMasTR prognostic test displays robust analytical performance that is suitable for deployment by local pathology laboratories for decentralized use.
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| 13. |
- Stapleton, L M, et al.
(författare)
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Microbial carbon dynamics in nitrogen amended Arctic tundra soil: Measurement and model testing
- 2005
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Ingår i: Soil Biology & Biochemistry. - : Elsevier BV. - 0038-0717. ; 37:11, s. 2088-2098
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Tidskriftsartikel (refereegranskat)abstract
- We examined the responses of grazers (protozoa and nematodes) and their main food sources to low levels of nitrogen (N) fertilisation and applied carbon (C) flux models to our data. Replicate plots of tundra soil adjacent to the Kongsfjorden (Svalbard 78°N) were amended with ammonium and nitrate at concentrations of 1 and 5 kg N ha−1 to assess the impact of anthropogenic N deposition over three summers. Bacterial abundance as determined using the fluorochrome SYBR Green and epifluorescence microscopy ranged between 9.73×108 and 102.49×108 cells/g dry wt of soil, with a significant response to N addition occurring only during the second sampling in 2001. Despite little change in bacterial biomass, bacterial production (measured by the incorporation of 3H thymidine into DNA) during the second sampling in 2002, increased in NH4 enriched plots compared to control and NO3 amended plots, indicating that NH4 was the preferred source of inorganic N. The main bacterial predators were heterotrophic flagellates (HNAN) and naked amoebae, which showed no significant response to the N addition. HNAN showed a correlation with bacterial abundance suggesting a dependence on bacteria as a food source. The inability of a microbial C flux model to fit our data (RWSS/data=18.6, r2=0.088) was at least partly due to insufficient bacterial production to meet the C demands of predator taxa, and high variability in the data over time. This is reflected in the performance statistics for model variants where select microbial taxa and data were removed. The optimal model in terms of predictive utility was a model with data from 2002 only, minus naked amoebae (RWSS/data=2.45, r2=0.806).
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| 14. |
- Gommenginger, Christine, et al.
(författare)
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SEASTAR: A mission to study ocean submesoscale dynamics and small-scale atmosphere-ocean processes in coastal, shelf and polar seas
- 2019
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6:JUL
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- High-resolution satellite images of ocean color and sea surface temperature reveal an abundance of ocean fronts, vortices and filaments at scales below 10 km but measurements of ocean surface dynamics at these scales are rare. There is increasing recognition of the role played by small scale ocean processes in ocean-atmosphere coupling, upper-ocean mixing and ocean vertical transports, with advanced numerical models and in situ observations highlighting fundamental changes in dynamics when scales reach 1 km. Numerous scientific publications highlight the global impact of small oceanic scales on marine ecosystems, operational forecasts and long-term climate projections through strong ageostrophic circulations, large vertical ocean velocities and mixed layer re-stratification. Small-scale processes particularly dominate in coastal, shelf and polar seas where they mediate important exchanges between land, ocean, atmosphere and the cryosphere e.g. freshwater, pollutants. As numerical models continue to evolve towards finer spatial resolution and increasingly complex coupled atmosphere-wave-ice-ocean systems, modern observing capability lags behind, unable to deliver the high-resolution synoptic measurements of total currents, wind vectors and waves needed to advance understanding, develop better parameterizations and improve model validations, forecasts and projections. SEASTAR is a satellite mission concept that proposes to directly address this critical observational gap with synoptic two-dimensional imaging of total ocean surface current vectors and wind vectors at 1 km resolution and coincident directional wave spectra. Based on major recent advances in squinted along-track Synthetic Aperture Radar interferometry, SEASTAR is an innovative, mature concept with unique demonstrated capabilities, seeking to proceed towards spaceborne implementation within Europe and beyond.
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| 17. |
- Lagali, Neil, et al.
(författare)
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Focused Tortuosity Definitions Based on Expert Clinical Assessment of Corneal Subbasal Nerves
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 56:9, s. 5102-5109
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. We examined agreement among experts in the assessment of corneal subbasal nerve tortuosity. METHODS. Images of corneal subbasal nerves were obtained from investigators at seven sites (Auckland, Boston, Linkoping, Manchester, Oslo, Rostock, and Sydney) using laser-scanning in vivo confocal microscopy. A set of 30 images was assembled and ordered by increasing tortuosity by 10 expert graders from the seven sites. In a first experiment, graders assessed tortuosity without a specific definition and performed grading three times, with at least 1 week between sessions. In a second experiment, graders assessed the same image set using four focused tortuosity definitions. Intersession and intergrader repeatability for the experiments were determined using the Spearman rank correlation. RESULTS. Expert graders without a specific tortuosity definition had high intersession (Spearman correlation coefficient 0.80), but poor intergrader (0.62) repeatability. Specific definitions improved intergrader repeatability to 0.79. In particular, tortuosity defined by frequent small-amplitude directional changes (short range tortuosity) or by infrequent large-amplitude directional changes (long range tortuosity), indicated largely independent measures and resulted in improved repeatability across the graders. A further refinement, grading only the most tortuous nerve in a given image, improved the average correlation of a given graders ordering of images with the group average to 0.86 to 0.90. CONCLUSIONS. Definitions of tortuosity specifying short or long-range tortuosity and considering only the most tortuous nerve in an image improved the agreement in tortuosity grading among a group of expert observers. These definitions could improve accuracy and consistency in quantifying subbasal nerve tortuosity in clinical studies.
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| 18. |
- MacEachen, Ellen, et al.
(författare)
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Scoping Review of Work Disability Policies and Programs
- 2017
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Ingår i: International Journal of Disability Mangement Research. - : Cambridge University Press. - 1833-8550 .- 1834-4887. ; 12, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This scoping review identifies the foci of research articles that address government laws, policies and programs designed to foster labour market integration of people who, due to illness or disability, face challenges entering or staying in the workforce. Method: A systematic search of English-language peer-reviewed articles published between 2000 and 2014 yielded 14,474 articles. Title and abstract review identified 723 included articles that addressed government-led programs, policy or legislation on work integration and/or income support after injury, illness or impairment. These were sorted by theme, work disability program or policy, disability type, jurisdiction and year published. Results: The number of articles published that address work disability laws, policies and programs increased steadily. Most articles addressed disability in general. Among articles with a specific health focus, mental health was the most common. Research gaps are identified for mixed method study designs, chronic and episodic conditions, illness and cancer, and for work disability policy studies outside of North America, Northern Europe and Australia. Conclusions: We find a growing number of published articles about work disability and policy and identify specific areas where is a need for further research. Copyright © 2017 The Author(s).
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| 19. |
- Stapleton, M. R., et al.
(författare)
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Identification of conserved antigens from staphylococcal and streptococcal pathogens
- 2012
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Ingår i: Journal of Medical Microbiology. - : Microbiology Society. - 0022-2615 .- 1473-5644. ; 61:6, s. 766-779
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Tidskriftsartikel (refereegranskat)abstract
- The design of vaccines containing epitopes shared between different human pathogens may lead to cross-species protection. In order to identify potentially conserved bacterial antigens, bacteriophage expression libraries of genomic DNA from Streptococcus agalactiae, Streptococcus pneumoniae and Streptococcus pyogenes were probed with human sera from Staphylococcus aureus-infected and healthy individuals. By comparison with previous screening data from Staphylococcus epidermidis and Staph. aureus, putative antigenic, conserved domains across the genera were identified. In particular, three potentially antigenic conserved regions were identified based on the N-terminal domain of SACOL0609 (SdrD), the C-terminal domain of SACOL0723 (ScaB) and the C-terminus of SACOL1140 (IsdA) from Staph. aureus. The three domains were overexpressed, recombinant proteins were purified and polyclonal antisera raised against them recognized cell surface-located proteins from both staphylococcal and streptococcal species. The antisera were also able to opsonize both Staph. aureus and Strep. agalactiae thereby increasing their phagocytic uptake by human neutrophils. The conserved antigenic domains therefore represent potential cross-protective vaccine candidates.
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