| 1. |
- Andersson, Tilde, et al.
(författare)
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Enrichment of antibiotic resistance genes within bacteriophage populations in saliva samples from individuals undergoing oral antibiotic treatments
- 2022
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Spread of antibiotic resistance is a significant challenge for our modern health care system, and even more so in developing countries with higher prevalence of both infections and resistant bacteria. Faulty usage of antibiotics has been pinpointed as a driving factor in spread of resistant bacteria through selective pressure. However, horizontal gene transfer mediated through bacteriophages may also play an important role in this spread. In a cohort of Tanzanian patients suffering from bacterial infections, we demonstrate significant differences in the oral microbial diversity between infected and non-infected individuals, as well as before and after oral antibiotics treatment. Further, the resistome carried both by bacteria and bacteriophages vary significantly, with blaCTX-M1 resistance genes being mobilized and enriched within phage populations. This may impact how we consider spread of resistance in a biological context, as well in terms of treatment regimes.
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| 2. |
- Bergström, Christel A. S., et al.
(författare)
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Early pharmaceutical profiling to predict oral drug absorption : Current status and unmet needs
- 2014
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 57, s. 173-199
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Tidskriftsartikel (refereegranskat)abstract
- Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmaceutical profiling methods available, with focus on in silica and in vitro models typically used to forecast active pharmaceutical ingredient's (APIs) in vivo performance after oral administration. An overview of the composition of human, animal and simulated gastrointestinal (GI) fluids is provided and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties are discussed in detail and future demands on pharmaceutical profiling are identified. It is expected that innovative computational and experimental methods that better describe molecular processes involved in vivo during dissolution and absorption of APIs will be developed in the OrBiTo. These methods will provide early insights into successful pathways (medicinal chemistry or formulation strategy) and are anticipated to increase the number of new APIs with good oral absorption being discovered. (C) 2013 Elsevier B.V. All rights reserved.
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| 3. |
- Fortuin-de Smidt, Melony C., et al.
(författare)
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Physical activity attenuates but does not eliminate coronary heart disease risk amongst adults with risk factors : EPIC-CVD case-cohort study
- 2022
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 29:12, s. 1618-1629
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: This study aimed to evaluate the association between physical activity and the incidence of coronary heart disease (CHD) in individuals with and without CHD risk factors.METHODS AND RESULTS: EPIC-CVD is a case-cohort study of 29 333 participants that included 13 582 incident CHD cases and a randomly selected sub-cohort nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Self-reported physical activity was summarized using the Cambridge physical activity index (inactive, moderately inactive, moderately active, and active). Participants were categorized into sub-groups based on the presence or the absence of the following risk factors: obesity (body mass index ≥30 kg/m2), hypercholesterolaemia (total cholesterol ≥6.2 mmol/L), history of diabetes, hypertension (self-reported or ≥140/90 mmHg), and current smoking. Prentice-weighted Cox regression was used to assess the association between physical activity and incident CHD events (non-fatal and fatal).Compared to inactive participants without the respective CHD risk factor (referent), excess CHD risk was highest in physically inactive and lowest in moderately active participants with CHD risk factors. Corresponding excess CHD risk estimates amongst those with obesity were 47% [95% confidence interval (CI) 32-64%] and 21% (95%CI 2-44%), with hypercholesterolaemia were 80% (95%CI 55-108%) and 48% (95%CI 22-81%), with hypertension were 80% (95%CI 65-96%) and 49% (95%CI 28-74%), with diabetes were 142% (95%CI 63-260%), and 100% (95%CI 32-204%), and amongst smokers were 152% (95%CI 122-186%) and 109% (95%CI 74-150%).CONCLUSIONS: In people with CHD risk factors, moderate physical activity, equivalent to 40 mins of walking per day, attenuates but does not completely offset CHD risk.
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| 4. |
- Isaksson Hallstedt, Sophie, 1969, et al.
(författare)
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Sustainable product development in aeroengine manufacturing: challenges, opportunities and experiences from GKN Aerospace Engine System
- 2023
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Ingår i: Design Science. - : Cambridge University Press. - 2053-4701. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- A radical shift in technology is necessary to enable future air transport solutions. Sustainability targets for aeroengine manufacturing mean more than reducing CO2 and NOX. The future will open up possibilities and bring new challenges when introducing hybrid- and electrical propulsion technologies using new materials, technology solutions and new business models. This article reports on findings from a longitudinal study and many years of collaboration between researchers and industry experts, where a first-tier aeroengine manufacturer transforms their product development capabilities to enable sustainable product development. The article highlights some activities undertaken and identifies critical challenges and opportunities remaining for a manufacturer of next-generation aeroengine solutions. It is argued that the challenge for aeroengine manufacturers to develop new-generation propulsive technologies will require a systemic change in the undertaking of design and development. The opportunities of sustainable technologies are evident yet require: (1) means to tighter integrate business and technology development, (2) the ability to quantify and assess sustainability impacts of different concept solutions, and (3) means to utilise natural resources, alloys and materials for a circular and life-cycle optimised solution.
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| 5. |
- Jorgensen, Jesper Roland, et al.
(författare)
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Cometin is a novel neurotrophic factor that promotes neurite outgrowth and neuroblast migration in vitro and supports survival of spiral ganglion neurons in vivo
- 2012
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886 .- 1090-2430. ; 233:1, s. 172-181
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Tidskriftsartikel (refereegranskat)abstract
- Neurotrophic factors are secreted proteins responsible for migration, growth and survival of neurons during development, and for maintenance and plasticity of adult neurons. Here we present a novel secreted protein named Cometin which together with Meteorin defines a new evolutionary conserved protein family. During early mouse development, Cometin is found exclusively in the floor plate and from E13.5 also in dorsal root ganglions and inner ear but apparently not in the adult nervous system. In vitro, Cometin promotes neurite outgrowth from dorsal root ganglion cells which can be blocked by inhibition of the Janus or MEK kinases. In this assay, additive effects of Cometin and Meteorin are observed indicating separate receptors. Furthermore, Cometin supports migration of neuroblasts from subventricular zone explants to the same extend as stromal cell derived factor la. Given the neurotrophic properties in vitro, combined with the restricted inner ear expression during development, we further investigated Cometin in relation to deafness. In neomycin deafened guinea pigs, two weeks intracochlear infusion of recombinant Cometin supports spiral ganglion neuron survival and function. In contrast to the control group receiving artificial perilymph, Cometin treated animals retain normal electrically-evoked brainstem response which is maintained several weeks after treatment cessation. Neuroprotection is also evident from stereological analysis of the spiral ganglion. Altogether, these studies show that Cometin is a potent new neurotrophic factor with therapeutic potential. (C) 2011 Elsevier Inc. All rights reserved.
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| 6. |
- Khoptyar, Dmitry, et al.
(författare)
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Broadband photon time-of-flight spectroscopy of pharmaceuticals and highly scattering plastics in the VIS and close NIR spectral ranges
- 2013
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Ingår i: Optics Express. - 1094-4087. ; 21:18, s. 20941-20953
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Tidskriftsartikel (refereegranskat)abstract
- We present extended spectroscopic analysis of pharmaceutical tablets in the close near infrared spectral range performed using broadband photon time-of-flight (PTOF) absorption and scattering spectra measurements. We show that the absorption spectra can be used to perform evaluation of the chemical composition of pharmaceutical tablets without need for chemo-metric calibration. The spectroscopic analysis was performed using an advanced PTOF spectrometer operating in the 650 to 1400 nm spectral range. By employing temporal stabilization of the system we achieve the high precision of 0.5% required to evaluate the concentration of tablet ingredients. In order to further illustrate the performance of the system, we present the first ever reported broadband evaluation of absorption and scattering spectra from pure and doped Spectralon (R). (C) 2013 Optical Society of America
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| 7. |
- Mjörnstedt, Lars, 1956, et al.
(författare)
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Renal function three years after early conversion from a calcineurin inhibitor to everolimus : results from a randomized trial in kidney transplantation
- 2015
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 28:1, s. 42-51
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Tidskriftsartikel (refereegranskat)abstract
- In a 36-month, open-label, multicenter trial, 202 kidney transplant recipients were randomized at week 7 post-transplant to convert to everolimus or remain on cyclosporine: 182 were analyzed to month 36 (92 everolimus, 90 controls). Mean (SD) change in measured GFR (mGFR) from randomization to month 36 was 1.3 (14.0)ml/min with everolimus versus -1.7 (15.4)ml/min in controls (P=0.210). In patients who remained on treatment, mean mGFR improved from randomization to month 36 by 7.9 (11.5)ml/min with everolimus (n=37) but decreased by 1.4 (14.7)ml/min in controls (n=62) (P=0.001). During months 12-36, death-censored graft survival was 100%, patient survival was 98.9% and 96.7% in the everolimus and control groups, respectively, and 13.0% and 11.1% of everolimus and control patients, respectively, experienced mild biopsy-proven acute rejection (BPAR). Protocol biopsies in a limited number of on-treatment patients showed similar interstitial fibrosis progression. Donor-specific antibodies were present at month 36 in 6.3% (2/32) and 18.0% (9/50) of on-treatment everolimus and control patients with available data (P=0.281). During months 12-36, adverse events were comparable, but discontinuation was more frequent with everolimus (33.7% vs. 10.0%). Conversion from cyclosporine to everolimus at 7weeks post-transplant was associated with a significant benefit in renal function at 3years when everolimus was continued.
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| 8. |
- Månsson, Fredrik, et al.
(författare)
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Trends of HIV-1 and HIV-2 prevalence among pregnant women in Guinea-Bissau, West Africa: possible effect of the civil war 1998-1999.
- 2007
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Ingår i: Sexually Transmitted Infections. - : BMJ. - 1368-4973. ; 83:6, s. 463-467
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Sentinel surveys in Bissau, the capital of Guinea-Bissau, have shown low prevalence of HIV-1 but high HIV-2 prevalence before 1998. Guinea-Bissau experienced a civil war in 1998-1999. To examine specifically the trends of HIV prevalence from antenatal surveys in Bissau, Guinea-Bissau in 1987-2004, and whether the civil war in 1998-1999 could have an effect on HIV prevalence levels after the conflict. Methods: Since 1987, anonymous HIV testing in delivering women has been performed at the maternity clinic, Simao Mendes National Hospital, Bissau, as part of the national sentinel surveillance programme. Consecutive sampling was performed for approximately 3 months between September and December each year. Serological analyses were performed at the National Public Health Laboratory in Guinea-Bissau. Results: A total of 20 422 women were tested for HIV between 1987 and 2004. The total HIV-1 prevalence increased from 0.0% in 1987 to 4.8% in 2004 and the total HIV-2 prevalence decreased from 8.3% in 1987 to 2.5% in 2004. The HIV-1 prevalence increased from 2.5% in 1997 to 5.2% in 1999, but stabilized in subsequent years. Conclusions: There was a significant increase in HIV-1 prevalence in the years 1987-2004 and a significant decline in HIV-2 prevalence over the same period. The civil war in 1998-1999 may have sparked HIV-1 transmission, as HIV-1 prevalence more than doubled between 1997 and 1999, but there is no evidence of a long-term effect on the trends of HIV-1 or HIV-2 prevalence.
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| 9. |
- Orlando, Ludovic, et al.
(författare)
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Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 499:7456, s. 74-
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Tidskriftsartikel (refereegranskat)abstract
- The rich fossil record of equids has made them a model for evolutionary processes(1). Here we present a 1.12-times coverage draft genome from a horse bone recovered from permafrost dated to approximately 560-780 thousand years before present (kyr BP)(2,3). Our data represent the oldest full genome sequence determined so far by almost an order of magnitude. For comparison, we sequenced the genome of a Late Pleistocene horse (43 kyr BP), and modern genomes of five domestic horse breeds (Equus ferus caballus), a Przewalski's horse (E. f. prze-walskii) and a donkey (E. asinus). Our analyses suggest that the Equus lineage giving rise to all contemporary horses, zebras and donkeys originated 4.0-4.5 million years before present (Myr BP), twice the conventionally accepted time to the most recent common ancestor of the genus Equus(4,5). We also find that horse population size fluctuated multiple times over the past 2 Myr, particularly during periods of severe climatic changes. We estimate that the Przewalski's and domestic horse populations diverged 38-72 kyr BP, and find no evidence of recent admixture between the domestic horse breeds and the Przewalski's horse investigated. This supports the contention that Przewalski's horses represent the last surviving wild horse population(6). We find similar levels of genetic variation among Przewalski's and domestic populations, indicating that the former are genetically viable and worthy of conservation efforts. We also find evidence for continuous selection on the immune system and olfaction throughout horse evolution. Finally, we identify 29 genomic regions among horse breeds that deviate from neutrality and show low levels of genetic variation compared to the Przewalski's horse. Such regions could correspond to loci selected early during domestication.
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| 10. |
- Poikonen-Saksela, Paula, et al.
(författare)
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Leukocyte nadir as a predictive factor for efficacy of adjuvant chemotherapy in breast cancer. Results from the prospective trial SBG 2000-1
- 2020
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 59:7, s. 825-832
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Tidskriftsartikel (refereegranskat)abstract
- Background: Retrospective studies have suggested that chemotherapy-induced leukopenia is associated with improved recurrence-free or overall survival. The SBG 2000-1 trial was designed to verify the favorable prognosis associated with chemotherapy-induced leukopenia in early breast cancer. Patients not experiencing chemotherapy-induced leukopenia were randomized into standard dosed or individually escalated chemotherapy doses based on the grade of leukopenia after a first standard dose.Patients and methods: 1452 women in Sweden and Denmark with operable node-positive or high-risk node-negative breast cancer aged 18-60 years were recruited to participate in this trial. Participants received a first FEC cycle at standard doses (600/60/600 mg/m(2)). Patients (n = 1052) with nadir leukopenia grade 0-2 after the first cycle were randomized between either 6 standard FEC or 6 tailored FEC courses with doses of epirubicin and cyclophosphamide escalated during courses 2 and 3 and thereafter aimed at achieving grade 3 leukopenia. Patients with nadir leukopenia grade 3-4 after the first course continued treatment with standard FEC. Results of the randomized comparison has been published previously. The present study focuses on chemotherapy-induced leukopenia as a covariable with outcome in randomized and non-randomized patients. The prognostic value of leukopenia after course 3, was studied in a Cox model adjusted for cumulative doses of epirubicin and cyclophosphamide. The association of chemotherapy-induced leukopenia with prognosis was a preplanned secondary endpoint for this trial.Results: The eight-year distant disease-free survival was 73%, 77%, 78% and 83% for patients with leucocyte nadir grade 0, 1, 2 and 3-4, respectively. Higher degree of leukopenia was highly significantly associated to improved distant disease-free survival (HR 0.84, 95% CI 0.74-0.96, p = .008) and overall survival (HR 0.87 (0.76-0.99, p = .032).Conclusion: This prospective study confirms that chemotherapy-induced leukopenia is a covariable with outcome in primary breast cancer, even after adjustment for chemotherapy doses.
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