| 1. |
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| 2. |
- Marcaide, J. M., et al.
(författare)
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Discovery of shell-like radio-structure in SN1993J
- 1995
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Ingår i: Nature. - London : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 373:6509, s. 44-45
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Tidskriftsartikel (refereegranskat)abstract
- SUPERNOVA explosions are poorly understood, partly because of difficulties in modelling them theoretically(1), and partly because there have been no supernovae observed in our Galaxy since the invention of the telescope. But the recent discovery(2) of supernova SN1993J in the nearby galaxy M81 offers an opportunity to investigate the evolution of the remnant, and its interaction with the surrounding interstellar medium, at high resolution. Here we present radio observations of SN1993J, made using very-long-baseline interferometry, which show the development of a shell structure. This 8-month-old radio shell is the youngest ever discovered in a supernova. The data suggest that the supernova explosion and the expanding shell of the remnant have nearly spherical symmetry, with small deviations where some parts of the shell are brighter than others. If these deviations arise because of variations in the density of the shell, this may reconcile earlier reports of symmetric radio emission(3) with the observed optical asymmetry(4,5), as the density variations could easily cause the latter. We infer that the radio emission is generated at the interface(6-9), where the surrounding gas is shocked by the ejecta.
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| 3. |
- Abu-Elyazeed, R R, et al.
(författare)
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Safety and immunogenicity of a glycoprotein D genital herpes vaccine in healthy girls 10-17 years of age : results from a randomised, controlled, double-blind trial
- 2013
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 31:51, s. 6136-6143
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The investigational AS04-adjuvanted herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit prophylactic vaccine ('HSV vaccine'; GlaxoSmithKline Vaccines) has been shown to be well tolerated in adults, but limited data exist for pre-teen and adolescent girls, a likely target population. The primary objective of this study was to compare the occurrence of serious adverse events (SAEs) over 12 months between HSV vaccine recipients and saline recipients (placebo control group) in pre-teen and adolescent girls. The immunogenicity of the HSV vaccine was also assessed.METHODS: Healthy girls aged 10-17 years, stratified by age (10-15 years; 16-17 years), were randomised 2:1:1 to receive the HSV vaccine, a hepatitis A vaccine (Havrix™; HAV control) or placebo (saline) according to a 0-, 1-, 6-month schedule. Participants and study personnel not involved in the preparation or administration of vaccines were blinded to treatment. Safety and immunogenicity analyses were performed overall and by age (10-15 years; 16-17 years) and HSV serostatus.RESULTS: No statistically significant difference in the percentage of subjects with SAEs was observed between the HSV and saline group, or between the HSV and pooled control (HAV and saline) groups. The HSV vaccine was well tolerated, although a higher incidence of solicited local symptoms was observed in the HSV group than in the control group. Neither age nor HSV serostatus at the time of study entry had an impact on the safety profile of this vaccine. The HSV vaccine was immunogenic regardless of pre-vaccination HSV serostatus. Higher anti-gD geometric mean concentrations were observed in HSV-1 seropositive participants than in HSV-1 seronegative participants.CONCLUSION: The HSV vaccine had an acceptable safety profile, and was well tolerated and immunogenic when administered to girls aged 10-17 years regardless of age or HSV pre-vaccination serostatus.
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| 4. |
- Fall, Magnus, 1941, et al.
(författare)
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Hunner lesion disease differs in diagnosis, treatment and outcome from bladder pain syndrome: an ESSIC working group report
- 2020
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 54:2, s. 91-98
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: There is confusion about the terms of bladder pain syndrome (BPS) and Interstitial Cystitis (IC). The European Society for the Study of IC (ESSIC) classified these according to objective findings [9]. One phenotype, Hunner lesion disease (HLD or ESSIC 3C) differs markedly from other presentations. Therefore, the question was raised as to whether this is a separate condition or BPS subtype. Methods: An evaluation was made to explore if HLD differs from other BPS presentations regarding symptomatology, physical examination findings, laboratory tests, endoscopy, histopathology, natural history, epidemiology, prognosis and treatment outcomes. Results: Cystoscopy is the method of choice to identify Hunner lesions, histopathology the method to confirm it. You cannot distinguish between main forms of BPS by means of symptoms, physical examination or laboratory tests. Epidemiologic data are incomplete. HLD seems relatively uncommon, although more frequent in older patients than non-HLD. No indication has been presented of BPS and HLD as a continuum of conditions, one developing into the other. Conclusions: A paradigm shift in the understanding of BPS/IC is urgent. A highly topical issue is to separate HLD and BPS: treatment results and prognoses differ substantially. Since historically, IC was tantamount to Hunner lesions and interstitial inflammation in the bladder wall, still, a valid definition, the term IC should preferably be reserved for HLD patients. BPS is a symptom syndrome without specific objective findings and should be used for other patients fulfilling the ESSIC definitions.
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| 5. |
- Home, P. D., et al.
(författare)
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Improved health status with insulin degludec compared with insulin glargine in people with Type 1 diabetes
- 2012
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Ingår i: Diabetic Medicine. - Hoboken, USA : Wiley-Blackwell. - 0742-3071 .- 1464-5491. ; 29:6, s. 716-720
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The efficacy and safety of insulin degludec (degludec), a new-generation ultra-long-acting basal insulin, was compared with insulin glargine (glargine) in people with Type 1 diabetes mellitus in a 16-week, open-label, randomized trial. Health status, an important aspect of effective diabetes management, was also assessed. Methods: Degludec (n = 59) or glargine (n = 59) were injected once daily, with insulin aspart at mealtimes. Health status assessment utilized the validated Short Form 36 Health Survey, version 2, which has two summary component scores for mental and physical well-being, each comprising four domains.Results: At study end, HbA1c reductions were comparable between groups, but confirmed nocturnal hypoglycaemia was significantly less frequent with degludec [relative rate 0.42 (95% CI 0.250.69)], and overall hypoglycaemia numerically less frequent [relative rate 0.72 (95% CI 0.521.00)]. After 16 weeks, a significant improvement in Short Form 36 Health Survey mental component score of +3.01 (95% CI 0.325.70) was obtained for degludec against glargine, attributable to significant differences in the social functioning [+8.04 (95% CI 1.8914.18)] and mental health domains [+2.46 (95% CI 0.104.82)]. For mental component score, Cohens effect size was 0.42, indicating a small-to-medium clinically meaningful difference. The physical component score [+0.66 (95% CI 2.30 to 3.62)] and remaining domains were not significantly different between degludec and glargine.Conclusions: In the context of comparable overall glycaemic control with glargine, degludec improved mental well-being as measured using the mental component score of the Short Form 36 Health Survey. The improvements in overall mental component score and the underlying social functioning and mental health domains with degludec compared with glargine may relate to the observed reduction in hypoglycaemic events.
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| 6. |
- Meltzer, E, et al.
(författare)
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Clinically relevant effect of a new intranasal therapy (MP29-02) in allergic rhinitis assessed by responder analysis
- 2013
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Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 161:4, s. 369-377
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> It is unclear what constitutes a clinically meaningful response for allergic rhinitis (AR) outcomes. The objectives of these post hoc analyses were (1) to define a clinically meaningful response using novel efficacy analyses (including a responder analysis), and (2) to compare the efficacy of MP29-02 [a novel intranasal formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP)] with commercially available FP, AZE and placebo in seasonal AR (SAR) patients, using these novel analyses. <b><i>Methods:</i></b> 610 moderate-to-severe SAR patients (≥12 years old) were randomized into a double-blind, placebo-controlled, 14-day, parallel-group trial. Change from baseline in the reflective total nasal symptom score (rTNSS) over 14 days was the primary outcome. Post hoc endpoints included the sum of nasal and ocular symptoms (rT7SS), efficacy by disease severity and by predominant nasal symptom, and a set of responder analyses. <b><i>Results:</i></b> MP29-02 most effectively reduced rT7SS (relative greater improvement: 52% to FP; 56% to AZE) and both nasal and ocular symptoms irrespective of severity. More MP29-02 patients achieved a ≥30, ≥50, ≥60, ≥75 and ≥90% rTNSS reduction, which occurred days faster than with either active comparator; MP29-02 alone was superior to placebo at the ≥60% (or higher) threshold. One in 2 MP29-02 patients achieved a ≥50% rTNSS reduction and 1 in 6 achieved complete/near-to-complete response. Only MP29-02 was consistently superior to placebo for all patients, whatever their predominant symptom. <b><i>Conclusions:</i></b> MP29-02 provided faster and more complete symptom control than first-line therapies. It was consistently superior irrespective of severity, response criteria or patient-type, and may be considered the drug of choice for moderate-to-severe AR. These measures define a new standard for assessing relevance in AR.
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| 7. |
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| 8. |
- Skyler, Jay S, et al.
(författare)
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Differentiation of diabetes by pathophysiology, natural history, and prognosis
- 2017
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:2, s. 241-255
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Forskningsöversikt (refereegranskat)abstract
- The American Diabetes Association, JDRF, the European Association for the Study of Diabetes, and the American Association of Clinical Endocrinologists convened a research symposium, "The Differentiation of Diabetes by Pathophysiology, Natural History and Prognosis" on 10-12 October 2015. International experts in genetics, immunology, metabolism, endocrinology, and systems biology discussed genetic and environmental determinants of type 1 and type 2 diabetes risk and progression, as well as complications. The participants debated how to determine appropriate therapeutic approaches based on disease pathophysiology and stage and defined remaining research gaps hindering a personalized medical approach for diabetes to drive the field to address these gaps. The authors recommend a structure for data stratification to define the phenotypes and genotypes of subtypes of diabetes that will facilitate individualized treatment.
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| 9. |
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| 10. |
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| 11. |
- Birkeland, Kare I., et al.
(författare)
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Insulin degludec in type 1 diabetes : a randomized controlled trial of a new-generation ultra-long-acting insulin compared with insulin glargine
- 2011
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 34:3, s. 661-665
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Insulin degludec (IDeg) is a basal insulin that forms soluble multihexamers after subcutaneous injection, resulting in an ultra-long action profile. We assessed the efficacy and safety of IDeg formulations administered once daily in combination with mealtime insulin aspart in people with type 1 diabetes.RESEARCH DESIGN AND METHODS: In this 16-week, randomized, open-label trial, participants (mean: 45.8 years old, A1C 8.4%, fasting plasma glucose [FPG] 9.9 mmol/L, BMI 26.9 kg/m(2)) received subcutaneous injections of IDeg(A) (600 mu mol/L; n = 59), IDeg(B) (900 mu mol/L; n = 60), or insulin glargine (IGlar; n = 59), all given once daily in the evening. Insulin aspart was administered at mealtimes.RESULTS: At 16 weeks, mean A1C was comparable for IDeg(A) (7.8 +/- 0.8%), IDeg(B) (8.0 +/- 1.0%), and IGlar (7.6 +/- 0.8%), as was FPG (8.3 +/- 4.0, 8.3 +/- 2.8, and 8.9 +/- 3.5 mmol/L, respectively). Estimated mean rates of confirmed hypoglycemia were 28% lower for IDeg(A) compared with IGlar (rate ratio [RR]: 0.72 [95% CI 0.52-1.00]) and 10% lower for IDeg(B) compared with IGlar (RR: 0.90 [0.65-1.24]); rates of nocturnal hypoglycemia were 58% lower for IDeg(A) (RR: 0.42 [0.25-0.69]) and 29% lower for IDeg(B) (RR: 0.71 [0.44-1.16]). Mean total daily insulin dose was similar to baseline. The frequency and pattern of adverse events was similar between insulin treatments.CONCLUSIONS: In this clinical exploratory phase 2 trial in people with type 1 diabetes, IDeg is safe and well tolerated and provides comparable glycemic control to IGlar at similar doses, with reduced rates of hypoglycemia.
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| 12. |
- Gonzalez, Betina, et al.
(författare)
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Endogenously elevated androgens alter the developmental programming of the hypothalamic-pituitary axis in male mice.
- 2011
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Ingår i: Molecular and cellular endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 332:1-2, s. 78-87
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Tidskriftsartikel (refereegranskat)abstract
- Transgenic male mice that express human chorionic gonadotropin (hCG) α and β subunits constitutively hypersecrete hCG and produce elevated levels of androgens. The aim of this study was to characterize the hypothalamic-pituitary function of these transgenic (hCGαβ+) males by focusing on FSH regulation. Serum FSH levels and pituitary mRNA expression of Fshb, Lhb, Cga, Gnrhr and Esr1 were reduced, whereas Fst expression was increased in prepubertal hCGαβ+ males as compared with wild-type. In the hypothalamus, Cyp19a1 expression, GnRH concentration and ex-vivo GnRH pulsatility were elevated in prepubertal hCGαβ+ mice, whereas Kiss1 expression was decreased prepubertally and Gad67 expression was elevated neonatally. The effect of androgens on the developmental programming of the hypothalamic-pituitary axis of hCGαβ+ males was evaluated by perinatal and prepubertal antiandrogen (flutamide) administration. Our studies identified a critical window between gestational day 18 and postnatal day 14, during which chronically elevated androgens and/or their locally produced metabolites activate the hypothalamus and concomitantly shut-down the gonadotropin axis.
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| 13. |
- Insel, Richard A, et al.
(författare)
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Staging Presymptomatic Type 1 Diabetes: A Scientific Statement of JDRF, the Endocrine Society, and the American Diabetes Association.
- 2015
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 38:10, s. 1964-1974
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Tidskriftsartikel (refereegranskat)abstract
- Insights from prospective, longitudinal studies of individuals at risk for developing type 1 diabetes have demonstrated that the disease is a continuum that progresses sequentially at variable but predictable rates through distinct identifiable stages prior to the onset of symptoms. Stage 1 is defined as the presence of β-cell autoimmunity as evidenced by the presence of two or more islet autoantibodies with normoglycemia and is presymptomatic, stage 2 as the presence of β-cell autoimmunity with dysglycemia and is presymptomatic, and stage 3 as onset of symptomatic disease. Adoption of this staging classification provides a standardized taxonomy for type 1 diabetes and will aid the development of therapies and the design of clinical trials to prevent symptomatic disease, promote precision medicine, and provide a framework for an optimized benefit/risk ratio that will impact regulatory approval, reimbursement, and adoption of interventions in the early stages of type 1 diabetes to prevent symptomatic disease.
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| 14. |
- Johansson, Gunnar, et al.
(författare)
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Effective in vivo targeting of the mammalian target of rapamycin pathway in malignant peripheral nerve sheath tumors.
- 2008
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Ingår i: Molecular Cancer Therapeutics. - 1535-7163 .- 1538-8514. ; 7:5, s. 1237-45
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Tidskriftsartikel (refereegranskat)abstract
- Malignant peripheral nerve sheath tumors (MPNST) are chemoresistant sarcomas with poor 5-year survival that arise in patients with neurofibromatosis type 1 (NF1) or sporadically. We tested three drugs for single and combinatorial effects on collected MPNST cell lines and in MPNST xenografts. The mammalian target of rapamycin complex 1 inhibitor RAD001 (Everolimus) decreased growth 19% to 60% after 4 days of treatment in NF1 and sporadic-derived MPNST cell lines. Treatment of subcutaneous sporadic MPNST cell xenografts with RAD001 significantly, but transiently, delayed tumor growth, and decreased vessel permeability within xenografts. RAD001 combined with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib caused additional inhibitory effects on growth and apoptosis in vitro, and a small but significant additional inhibitory effect on MPNST growth in vivo that were larger than the effects of RAD001 with doxorubicin. RAD001 plus erlotinib, in vitro and in vivo, reduced phosphorylation of AKT and total AKT levels, possibly accounting for their additive effect. The results support the consideration of RAD001 therapy in NF1 patient and sporadic MPNST. The preclinical tests described allow rapid screening strata for drugs that block MPNST growth, prior to tests in more complex models, and should be useful to identify drugs that synergize with RAD001.
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| 15. |
- Kwon, J. Y., et al.
(författare)
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Growth mixture models: a case example of the longitudinal analysis of patient‐reported outcomes data captured by a clinical registry
- 2021
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Ingår i: BMC Medical Research Methodology. - : Springer Science and Business Media LLC. - 1471-2288. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: An assumption in many analyses of longitudinal patient-reported outcome (PRO) data is that there is a single population following a single health trajectory. One approach that may help researchers move beyond this traditional assumption, with its inherent limitations, is growth mixture modelling (GMM), which can identify and assess multiple unobserved trajectories of patients’ health outcomes. We describe the process that was undertaken for a GMM analysis of longitudinal PRO data captured by a clinical registry for outpatients with atrial fibrillation (AF). Methods: This expository paper describes the modelling approach and some methodological issues that require particular attention, including (a) determining the metric of time, (b) specifying the GMMs, and (c) including predictors of membership in the identified latent classes (groups or subtypes of patients with distinct trajectories). An example is provided of a longitudinal analysis of PRO data (patients’ responses to the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) Questionnaire) collected between 2008 and 2016 for a population-based cardiac registry and deterministically linked with administrative health data. Results: In determining the metric of time, multiple processes were required to ensure that “time” accounted for both the frequency and timing of the measurement occurrences in light of the variability in both the number of measures taken and the intervals between those measures. In specifying the GMM, convergence issues, a common problem that results in unreliable model estimates, required constrained parameter exploration techniques. For the identification of predictors of the latent classes, the 3-step (stepwise) approach was selected such that the addition of predictor variables did not change class membership itself. Conclusions: GMM can be a valuable tool for classifying multiple unique PRO trajectories that have previously been unobserved in real-world applications; however, their use requires substantial transparency regarding the processes underlying model building as they can directly affect the results and therefore their interpretation. © 2021, The Author(s).
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| 16. |
- Kwon, J. Y., et al.
(författare)
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Patient-reported outcomes and the identification of subgroups of atrial fibrillation patients: a retrospective cohort study of linked clinical registry and administrative data
- 2021
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Ingår i: Quality of Life Research. - : Springer Science and Business Media LLC. - 0962-9343 .- 1573-2649. ; 30, s. 1547-1559
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Previous research about the health and quality of life of people with atrial fibrillation has typically identified a single health trajectory. Our study aimed to examine variability in health trajectories and patient characteristics associated with such variability. Methods We conducted a retrospective analysis of data collected between 2008 and 2016 for a cardiac registry in British Columbia (Canada) linked with administrative health data. The Atrial Fibrillation Effect on Quality of Life Questionnaire was used to measure health status at up to 10 clinic visits. Growth mixture models were used and a three-step multinomial logistic regression was conducted to identify predictors of subgroups with different trajectories. Results The patients (N = 7439) were primarily men (61.1%) over 60 years of age (72.9%). Three subgroups of health status trajectories were identified: "poor but improving", "good and stable", and "excellent and stable" health. Compared with the other two groups, patients in the "poor but improving group" were more likely to (1) be less than 60 years of age; (2) be women; (3) have greater risk of stroke; (4) have had ablation therapy within 6 months to 1 year or more than 2 years after their initial consultation; and (5) have had anticoagulation therapy within 6 months. Conclusion Using growth mixture models, we found that not all health trajectories are the same. These models can help to understand variability in trajectories with different patient characteristics that could inform tailored interventions and patient education strategies.
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| 17. |
- Milathianaki, D., et al.
(författare)
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Femtosecond Visualization of Lattice Dynamics in Shock-Compressed Matter
- 2013
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 342:6155, s. 220-223
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Tidskriftsartikel (refereegranskat)abstract
- The ultrafast evolution of microstructure is key to understanding high-pressure and strain-rate phenomena. However, the visualization of lattice dynamics at scales commensurate with those of atomistic simulations has been challenging. Here, we report femtosecond x-ray diffraction measurements unveiling the response of copper to laser shock-compression at peak normal elastic stresses of similar to 73 gigapascals (GPa) and strain rates of 10(9) per second. We capture the evolution of the lattice from a one-dimensional (1D) elastic to a 3D plastically relaxed state within a few tens of picoseconds, after reaching shear stresses of 18 GPa. Our in situ high-precision measurement of material strength at spatial (<1 micrometer) and temporal (<50 picoseconds) scales provides a direct comparison with multimillion-atom molecular dynamics simulations.
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| 18. |
- Ranstam, Jonas, et al.
(författare)
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Oral-Contraceptive Use and the Risk of Breast Cancer
- 1987
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 316:3, s. 162-164
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Tidskriftsartikel (refereegranskat)abstract
- To the Editor: The study on oral-contraceptive use and the risk of breast cancer from the Centers for Disease Control (CDC) and the National Institute of Child Health and Human Development (Aug. 14 issue)1 seems to be reassuring for oral-contraceptive users. But, as stated in the editorial by Shapiro in the same issue,2 there are some weak points that need further elucidation. We have found a highly increased risk of breast cancer among young (teenage) oral-contraceptive users in southern Sweden.3 From incidence figures for Sweden, an increase in premenopausal breast cancer can be seen to have started in about 1975,…
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| 19. |
- Williams, Jon P, et al.
(författare)
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Nf1 mutation expands an EGFR-dependent peripheral nerve progenitor that confers neurofibroma tumorigenic potential.
- 2008
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Ingår i: Cell stem cell. - : Elsevier BV. - 1875-9777 .- 1934-5909. ; 3:6, s. 658-69
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Tidskriftsartikel (refereegranskat)abstract
- Defining growth factor requirements for progenitors facilitates their characterization and amplification. We characterize a peripheral nervous system embryonic dorsal root ganglion progenitor population using in vitro clonal sphere-formation assays. Cells differentiate into glial cells, smooth muscle/fibroblast (SM/Fb)-like cells, and neurons. Genetic and pharmacologic tools revealed that sphere formation requires signaling from the EGFR tyrosine kinase. Nf1 loss of function amplifies this progenitor pool, which becomes hypersensitive to growth factors and confers tumorigenesis. DhhCre;Nf1(fl/fl) mouse neurofibromas contain a progenitor population with similar growth requirements, potential, and marker expression. In humans, NF1 mutation predisposes to benign neurofibromas, incurable peripheral nerve tumors. Prospective identification of human EGFR(+);P75(+) neurofibroma cells enriched EGF-dependent sphere-forming cells. Neurofibroma spheres contain glial-like progenitors that differentiate into neurons and SM/Fb-like cells in vitro and form benign neurofibroma-like lesions in nude mice. We suggest that expansion of an EGFR-expressing early glial progenitor contributes to neurofibroma formation.
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