| 41. |
- Ridker, P. M., et al.
(författare)
-
Antiinflammatory therapy with canakinumab for atherosclerotic disease
- 2017
-
Ingår i: New England Journal of Medicine. - 0028-4793. ; 377:12, s. 1119-1131
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. Copyright © 2017 Massachusetts Medical Society.
|
|
| 42. |
- Tartaglia, Leonardo, et al.
(författare)
-
The Early Discovery of SN 2017ahn : Signatures of Persistent Interaction in a Fast-declining Type II Supernova
- 2021
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 907:1
-
Tidskriftsartikel (refereegranskat)abstract
- We present high-cadence, comprehensive data on the nearby (D 33 Mpc) Type II supernova (SN II) 2017ahn, discovered within about one day of the explosion, from the very early phases after explosion to the nebular phase. The observables of SN 2017ahn show a significant evolution over the 470 days of our follow-up campaign, first showing prominent, narrow Balmer lines and other high-ionization features purely in emission (i.e., flash spectroscopy features), which progressively fade and lead to a spectroscopic evolution similar to that of more canonical SNe II. Over the same period, the decline of the light curves in all bands is fast, resembling the photometric evolution of linearly declining H-rich core-collapse SNe. The modeling of the light curves and early flash spectra suggests that a complex circumstellar medium surrounds the progenitor star at the time of explosion, with a first dense shell produced during the very late stages of its evolution that is swept up by the rapidly expanding ejecta within the first ~6 days of the SN evolution, while signatures of interaction are observed also at later phases. Hydrodynamical models support the scenario in which linearly declining SNe II are predicted to arise from massive yellow super- or hypergiants depleted of most of their hydrogen layers.
|
|
| 43. |
- Cederroth, CR, et al.
(författare)
-
Medicine in the Fourth Dimension
- 2019
-
Ingår i: Cell metabolism. - : Elsevier BV. - 1932-7420 .- 1550-4131. ; 30:2, s. 238-250
-
Tidskriftsartikel (refereegranskat)
|
|
| 44. |
- Deutsch, Barbara, et al.
(författare)
-
Denitrification in sediments as a major nitrogen sink in the Baltic Sea : an extrapolation using sediment characteristics
- 2010
-
Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 7:10, s. 3259-3271
-
Tidskriftsartikel (refereegranskat)abstract
- Rates of denitrification in sediments were measured with the isotope pairing technique at different sites in the southern and central Baltic Sea. The rates varied between 0.5 mu mol N m(-2) h(-1) in sands and 28.7 mu mol N m(-2) h-1 in muddy sediments and showed a good correlation to the organic carbon contents of the surface sediments. N-removal rates via sedimentary denitrification were estimated for the entire Baltic Sea calculating sediment specific denitrification rates and interpolating them to the whole Baltic Sea area. Another approach was carried out by using the relationship between the organic carbon content and the rate of denitrification. The N-removal by denitrification in sediments varied between 426-652 kt Na-1, which is around 48-73% of the external N inputs delivered via rivers, coastal point sources, and atmospheric deposition. Moreover, an expansion of the anoxic bottom areas was considered under the assumption of a rising oxycline from 100 to 80 m water depth. This leads to an increase of the area with anoxic conditions and an overall decrease in sedimentary denitrification by 14%. Overall, we show here that this type of data extrapolation is a powerful tool to estimate the nitrogen losses for a whole coastal sea and may be applicable to other coastal regions and enclosed seas.
|
|
| 45. |
|
|
| 46. |
- Forster, M., et al.
(författare)
-
Assembly of Chiral Amino-Acids at Surfaces from a Single Molecule Perspective: Proline on Cu(110)
- 2011
-
Ingår i: Topics in Catalysis. - : Springer Science and Business Media LLC. - 1572-9028 .- 1022-5528. ; 54:1-4, s. 13-19
-
Tidskriftsartikel (refereegranskat)abstract
- We present a molecule-by-molecule mapping of an amino-acid monolayer on a Cu(110) surface in which individual molecular configuration, bonding and adsorption footprints are identified. This detailed mapping provides direct evidence that the (4 x 2) structures of enantiopure and racemic proline are governed by a strict heterochiral adsorption footprint template. For the racemic system this has an interesting consequence, namely that it leads to a 2-D random solid solution, a situation that is rarely encountered in 3-D.
|
|
| 47. |
- Forster, M., et al.
(författare)
-
Mapping Complex Chiral Adlayers: A Truly Random 2-D Solid Solution of (RS)-3-Pyrroline-2-Carboxylic Acid on Cu(110)
- 2011
-
Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 115:4, s. 1180-1185
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The characterization of chiral molecular adlayers remains a considerable challenge, ultimately requiring detailed knowledge of the molecular chirality, the chemical form, molecular orientation, and interaction with the surface for each molecule within the assembly. In this work, we show that the (4 x 2) organization of a racemic mixture of the amino acid derivative 3-pyrroline-2-carboxylic acid (PCA) on Cu(110) may be analyzed at the single-molecule level in which the molecular chirality and adsorption footprints of each molecule are identified. Such a detailed mapping reveals the surprising outcome that within the racemic (4 x 2) organization the adlayer does not form either the 2-D racemic compound or racemic conglomerate. Instead, both the molecular chirality and adsorption footprints are randomly distributed, creating a truly random solid solution in which both molecular chirality and footprint chirality are scrambled.
|
|
| 48. |
- Forster, M., et al.
(författare)
-
Probing Conformer and Adsorption Footprint Distributions at the Single-Molecule Level in a Highly Organised Amino-Acid Assembly of (S)-Proline on Cu(110)
- 2009
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 131:29, s. 10173-10181
-
Tidskriftsartikel (refereegranskat)abstract
- Establishing the nanoscale details of organized amino acid assemblies at surfaces is a major challenge in the field of organic-inorganic interfaces. Here, we show that the dense (4 x 2) overlayer of the amino acid, (S)-proline on a Cu(110) surface can be explored at the single-molecule level by scanning tunneling microscopy (STM), reflection absorption infrared spectroscopy (RAIRS), and periodic density functional theory (DFT) calculations. The combination of experiment and theory, allied with the unique structural rigidity of proline, enables the individual conformers and adsorption footprints adopted within the organized assembly to be determined. Periodic DFT calculations find two energetically favorable molecular conformations, projecting mirror-image chiral adsorption footprints at the surface. These two forms can be experimentally distinguished since the positioning of the amino group within the pyrrolidine ring leads each chiral footprint and associated conformer to adopt very different ring orientations, producing distinct contrasts in the STM images. DFT modeling shows that the two conformers can generate eight possible (4 x 2) overlayers with a variety of adsorption footprint arrangements. STM images simulated for each structural model enables a direct comparison to be made with the experiment and narrows the (4 x 2) overlayer to one specific structural model in which the juxtaposition of molecules leads to the formation of one-dimensional hydrogen bonded prolate chains directed along the [1 (1) over bar0] direction.
|
|
| 49. |
- Forster, M., et al.
(författare)
-
Tailoring Homochirality at Surfaces: Going Beyond Molecular Handedness
- 2011
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 133:40, s. 15992-16000
-
Tidskriftsartikel (refereegranskat)abstract
- Chirality can be bestowed upon a surface by the adsorption of molecules and is usually discussed in terms of the molecular handedness. However, the adsorption process often leads to a new manifestation of chirality in the form of the adsorption footprint, which can also be chiral and generate mirror-images in 2-D. Therefore, in describing the chirality of the interface, one must consider both the handedness and the adsorption 'footedness' of the system. Specifically, the creation of a truly homochiral surface must ensure that a single chirality is expressed for each aspect, and requires not only the control of molecule handedness but also direct control over footedness. Here, we demonstrate the ability to engineer homochiral footedness by a structural modification of enantiopure (S)-proline, which normally creates a (4 x 2) organization on a Cu(110) surface with heterochiral footedness. This modification of proline via the addition of a double bond within the pyrrolidine ring, yielding 3-pyrroline-2-carboxylic acid (PCA), is sufficient to drive the footprints of the entire (4 x 2) assembly from heterochiral to homochiral, leading to the creation of a truly homochiral interface The effects of modifications upon the footprint arrangements were characterized at the single-molecule level by scanning tunnelling microscopy, reflection absorption infrared spectroscopy and periodic density functional theory calculations. The control of adsorption footprints is not only pivotal to tailoring chirality at surfaces but also plays a key role in dictating the organization, the outward facing functionalities and the response of the organic-inorganic interface.
|
|
| 50. |
- Forster, T, et al.
(författare)
-
Cetuximab in Pancreatic Cancer Therapy: A Systematic Review and Meta-Analysis
- 2020
-
Ingår i: Oncology. - : S. Karger AG. - 1423-0232 .- 0030-2414. ; 98:1, s. 53-60
-
Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> The present study evaluated the potential benefit of adding cetuximab to neoadjuvant, adjuvant, or palliative standard therapy for pancreatic cancer. <b><i>Methods:</i></b> A systematic literature search was performed in MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL). Only randomised controlled trials (RCTs) investigating the effect of adding cetuximab to standard chemotherapy in pancreatic cancer were included. Evaluated outcomes were overall survival, progression-free survival, objective response, and toxicity. For overall survival and progression-free survival, hazard ratios (HR) with 95% confidence intervals (CI) were chosen as effect measure. For objective response, odds ratios (OR) with 95% CI were used. Analysis was based on a random effects model. <b><i>Results:</i></b> After screening 568 publications, a total of 4 RCTs with 924 patients were included. In all trials, patients were adequately randomised with balanced intervention and control groups. There was no significant difference in overall survival (HR 1.04; 95% CI: 0.90–1.19; <i>p</i> = 0.60), progression-free survival (HR 1.06; 95% CI: 0.93–1.22; <i>p</i> = 0.36), or objective response (OR 0.99; 95% CI: 0.66 –1.49; <i>p</i> = 0.96) when adding cetuximab to a standard therapy. Toxicity was the same or higher in each of the included trials. According to GRADE, the certainty of the evidence is high. Therefore, adding cetuximab to pancreatic cancer therapy has no clinically relevant benefit. <b><i>Conclusion:</i></b> In the presence of no survival benefit, increased toxicity, and higher costs, a decreased cost-benefit ratio compared to the standard care must be suggested. Conducting further RCTs in unselected pancreatic cancer populations is unlikely to change this conclusion.
|
|
