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- Su, Zhan, et al.
(författare)
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Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
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Tidskriftsartikel (refereegranskat)abstract
- Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
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| 4. |
- Cortina-Gil, D., et al.
(författare)
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CALIFA, a Dedicated Calorimeter for the R3B/FAIR
- 2014
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Ingår i: Nuclear Data Sheets. - : Elsevier BV. - 1095-9904 .- 0090-3752. ; 120, s. 99-101
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Tidskriftsartikel (refereegranskat)abstract
- The R3B experiment (Reactions with Relativistic Radioactive Beams) at FAIR (Facility for Antiproton and Ion Research) is a versatile setup dedicated to the study of reactions induced by high-energy radioactive beams. It will provide kinematically complete measurements with high efficiency, acceptance and resolution, making possible a broad physics program with rare-isotopes. CALIFA (CALorimeter for In-Flight detection of gamma-rays and high energy charged pArticles), is a complex detector based on scintillation crystals, that will surround the target of the R3B experiment. CALIFA will act as a total absorption gamma-calorimeter and spectrometer, as well as identifier of charged particles from target residues. This versatility is its most challenging requirement, demanding a huge dynamic range, to cover from low energy gamma-rays up to 300 MeV protons. This fact, along with the high-energy of the beams determine the conceptual design of the detector, presented in this paper, together with the technical solutions proposed for its construction.
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| 5. |
- Cortina-Gil, D., et al.
(författare)
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CALIFA, a Dedicated Calorimeter for the (RB)-B-3/FAIR
- 2014
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Ingår i: Nuclear Data Sheets. - : Elsevier BV. - 0090-3752. ; 120, s. 99-101
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Tidskriftsartikel (refereegranskat)abstract
- The (RB)-B-3 experiment (Reactions with Relativistic Radioactive Beams) at FAIR (Facility for Antiproton and Ion Research) is a versatile setup dedicated to the study of reactions induced by high-energy radioactive beams. It will provide kinematically complete measurements with high efficiency, acceptance and resolution, making possible a broad physics program with rare-isotopes. CALIFA (CALorimeter for In-Flight detection of gamma-rays and high energy charged pArticles), is a complex detector based on scintillation crystals, that will surround the target of the (RB)-B-3 experiment. CALIFA will act as a total absorption gamma-calorimeter and spectrometer, as well as identifier of charged particles from target residues. This versatility is its most challenging requirement, demanding a huge dynamic range, to cover from low energy gamma-rays up to 300 MeV protons. This fact, along with the high-energy of the beams determine the conceptual design of the detector, presented in this paper, together with the technical solutions proposed for its construction.
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| 6. |
- Lehtonen, PK, et al.
(författare)
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Candidate genes for colour and vision exhibit signals of selection across the pied flycatcher (Ficedula hypoleuca) breeding range
- 2012
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Ingår i: Heredity. - : Springer Science and Business Media LLC. - 1365-2540 .- 0018-067X. ; 108:4, s. 431-440
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Tidskriftsartikel (refereegranskat)abstract
- The role of natural selection in shaping adaptive trait differentiation in natural populations has long been recognized. Determining its molecular basis, however, remains a challenge. Here, we search for signals of selection in candidate genes for colour and its perception in a passerine bird. Pied flycatcher plumage varies geographically in both its structural and pigment-based properties. Both characteristics appear to be shaped by selection. A single-locus outlier test revealed 2 of 14 loci to show significantly elevated signals of divergence. The first of these, the follistatin gene, is expressed in the developing feather bud and is found in pathways with genes that determine the structure of feathers and may thus be important in generating variation in structural colouration. The second is a gene potentially underlying the ability to detect this variation: SWS1 opsin. These two loci were most differentiated in two Spanish pied flycatcher populations, which are also among the populations that have the highest UV reflectance. The follistatin and SWS1 opsin genes thus provide strong candidates for future investigations on the molecular basis of adaptively significant traits and their co-evolution.
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| 7. |
- Nielsen, Niklas, et al.
(författare)
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Targeted Temperature Management at 33 degrees C versus 36 degrees C after Cardiac Arrest
- 2013
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 369:23, s. 2197-2206
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundUnconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. MethodsIn an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33 degrees C or 36 degrees C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. ResultsIn total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33 degrees C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36 degrees C group (225 of 466 patients) (hazard ratio with a temperature of 33 degrees C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33 degrees C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36 degrees C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. ConclusionsIn unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33 degrees C did not confer a benefit as compared with a targeted temperature of 36 degrees C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916.)
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| 8. |
- Schilke, P., et al.
(författare)
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Ubiquitous Argonium, ArH+, in the Diffuse Interstellar Medium
- 2014
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Ingår i: 13th International HITRAN Conference, Cambridge MA, USA.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- ArH+ is isoelectronic with HCl. The J = 1-0 and 2-1 transitions of 36ArH+ near 617.5 and 1234.6 GHz, respectively, have been identified very recently as emission lines in spectra obtained with Herschel toward the Crab Nebula supernova remnant.1 On Earth, 40Ar is by far the most abundant isotope, being almost exclusively formed by the radioactive decay of 40K. However, 36Ar is the dominant isotope in the Universe.In the course of unbiased line surveys of the massive and very luminous Galactic Center star-forming regions Sagittarius B2(M) and (N) with the high-resolution instrument HIFI on board of Herschel, we detected the J = 1-0 transition of 36ArH+ as a moderately strong absorption line initially associated with an unidentified carrier.2 In both cases, the absorption feature is unique in its appearance at all velocity components associated with diffuse foreground molecular clouds, together with its conspicuous absence at velocities related to the denser sources themselves. Model calculations are able to reproduce the derived ArH+ column densities and suggest that argonium resides in the largely atomic, diffuse interstellar medium with a molecular fraction of no more than ˜10-3. The 38ArH+ isotopologue was also detected.Subsequent observations toward the continuum sources W51, W49, W31C, and G34.3+0.1 resulted in unequivocal detections of 36ArH+ absorption. Hence, argonium is a good probe of the transition zone between atomic and molecular gas, in particular in combination with OH+ and H2O+, whose abundances peak at a molecular fraction of ˜0.1. Moreover, argonium is a good indicator of an enhanced cosmic ray ionization rate. Therefore, it may be prominent toward, e.g., active galactic nuclei (AGNs) in addition to supernova remnants.
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| 9. |
- Schilke, P., et al.
(författare)
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Ubiquitous argonium (ArH$^{+}$) in the diffuse interstellar medium: A molecular tracer of almost purely atomic gas
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 566:June, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Aims: We describe the assignment of a previously unidentified interstellar absorption line to ArH+ and discuss its relevance in the context of hydride absorption in diffuse gas with a low H2 fraction. The confidence of the assignment to ArH+ is discussed, and the column densities are determined toward several lines of sight. The results are then discussed in the framework of chemical models, with the aim of explaining the observed column densities. Methods: We fitted the spectral lines with multiple velocity components, and determined column densities from the line-to-continuum ratio. The column densities of ArH+ were compared to those of other species, tracing interstellar medium (ISM) components with different H2 abundances. We constructed chemical models that take UV radiation and cosmic ray ionization into account. Results: Thanks to the detection of two isotopologues, 36ArH+ and 38ArH+, we are confident about the carrier assignment to ArH+. NeH+ is not detected with a limit of [NeH+]/[ArH+] ≤ 0.1. The derived column densities agree well with the predictions of chemical models. ArH+ is a unique tracer of gas with a fractional H2 abundance of 10-4 - 10-3 and shows little correlation to H2O+, which traces gas with a fractional H2 abundance of ≈0.1. Conclusions: A careful analysis of variations in the ArH+, OH+, H2O+, and HF column densities promises to be a faithful tracer of the distribution of the H2 fractional abundance by providing unique information on a poorly known phase in the cycle of interstellar matter and on its transition from atomic diffuse gas to dense molecular gas traced by CO emission. Abundances of these species put strong observational constraints upon magnetohydrodynamical (MHD)simulations of the interstellar medium, and potentially could evolve into a tool characterizing the ISM. Paradoxically, the ArH+ molecule is a better tracer of almost purely atomic hydrogen gas than Hi itself, since Hi can also be present in gas with a significant molecular content, but ArH+ singles out gas that is >99.9% atomic.
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| 14. |
- Nielsen, Niklas, et al.
(författare)
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Detailed statistical analysis plan for the target temperature management after out-of-hospital cardiac arrest trial
- 2013
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Animal experimental studies and previous randomized trials suggest an improvement in mortality and neurological function with temperature regulation to hypothermia after cardiac arrest. According to a systematic review, previous trials were small, had a risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management (TTM) strategy is not known. To prevent outcome reporting bias, selective reporting and data-driven results, we present the a priori defined detailed statistical analysis plan as an update to the previously published outline of the design and rationale for the TTM trial. Methods: The TTM trial is an investigator-initiated, multicenter, international, randomized, parallel-group, and assessor-blinded clinical trial of temperature management in 950 adult unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause. The patients are randomized to a TTM of either 33 degrees C or 36 degrees C after return of spontaneous circulation. The primary outcome is all-cause mortality at maximal follow-up (until end of the trial and a minimum of 180 days). The main secondary outcomes are the composite outcome of all-cause mortality and poor neurological function (Cerebral Performance Category (CPC) 3 and 4, and modified Rankin Scale (mRS) 4 and 5) at hospital discharge and at 180 days; and assessment of safety and harm: bleeding, infections, electrolyte and metabolic disorders, seizures, cardiac arrhythmia, and renal replacement therapy. Conclusion: The TTM trial investigates potential benefit and harm of two target temperature strategies, both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population.
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| 15. |
- Perner, Anders, et al.
(författare)
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Hydroxyethyl Starch 130/0.4 versus Ringer's Acetate in Severe Sepsis
- 2012
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 367:2, s. 124-134
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Hydroxyethyl starch (HES) 130/0.4 is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis. METHODS In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.4 or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization. RESULTS Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.4 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.4 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline. CONCLUSIONS Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.4 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate.
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