Hunting for Primordial Non-Gaussianity in the Cosmic Microwave Background

Since the first limit on the (local) primordial non-Gaussianity parameter, fNL, was obtained from COBE data in 2002, observations of the CMB have been playing a central role in constraining the amplitudes of various forms of non-Gaussianity in primordial fluctuations. The current 68% limit from the 7-year WMAP data is fNL=32+/-21, and the Planck satellite is expected to reduce the uncertainty by a factor of four in a few years from now. If fNL>>1 is found by Planck with high statistical significance, all single-field models of inflation would be ruled out. Moreover, if the Planck satellite finds fNL=30, then it would be able to test a broad class of multi-field models using the four-point function (trispectrum) test of tauNL>=(6fNL/5)^2. In this article, we review the methods (optimal estimator), results (WMAP 7-year), and challenges (secondary anisotropy, second-order effect, and foreground) of measuring primordial non-Gaussianity from the CMB data, present a science case for the trispectrum, and conclude with future prospects.Comment: 33 pages, 4 figures. Invited review, accepted for publication in the CQG special issue on nonlinear cosmological perturbations. (v2) References added. More clarifications are added to the second-order effect and the multi-field consistency relation, tauNL>=(6fNL/5)^2

Biology of moderately halophilic aerobic bacteria

The moderately halophilic heterotrophic aerobic bacteria form a diverse group of microorganisms. The property of halophilism is widespread within the bacterial domain. Bacterial halophiles are abundant in environments such as salt lakes, saline soils, and salted food products. Most species keep their intracellular ionic concentrations at low levels while synthesizing or accumulating organic solutes to provide osmotic equilibrium of the cytoplasm with the surrounding medium. Complex mechanisms of adjustment of the intracellular environments and the properties of the cytoplasmic membrane enable rapid adaptation to changes in the salt concentration of the environment. Approaches to the study of genetic processes have recently been developed for several moderate halophiles, opening the way toward an understanding of haloadaptation at the molecular level. The new information obtained is also expected to contribute to the development of novel biotechnological uses for these organisms

Effect of cellulose nanofiber dimensions on sheet forming through filtration

Four different cellulose nanofibers samples were prepared from northern bleached softwood kraft fibers. Fiber diameter distributions were measured from SEM images. Fiber aspect ratios ranging from 84 to 146 were estimated from fiber suspension sedimentation measurements. Three samples had heterogeneous distributions of fiber diameters, while one sample was more homogeneous. Sheet forming experiments using filters with pores ranging from 150 to 5 μm showed that the samples with a heterogeneous distribution of fiber dimensions could be easily formed into sheets at 0. 2% initial solids concentration with all filter openings. On the other hand, sheets could only be formed from the homogenous sample by using 0. 5% or more initial solids content and a lower applied vacuum and smaller filter openings. The forming data and estimated aspect ratios show reasonable agreement with the predictions of the crowding number and percolation theories for the connectivity and rigidity thresholds for fiber suspensions

P571 Vedolizumab (VDZ) real-world outcomes in ulcerative colitis (UC)

Background: In GEMINI 1, UC response to vedolizumab (VDZ) was 47% at Week 6 and 42% by Week 52. Our aim was to assess real-life outcomes for VDZ in UC. Methods: Data collected at 12 Australian (Aus), 1 UK and 2 Hong Kong (HK) centres, assessed response to VDZ at 3, 6, and 12 months using the Mayo Clinic Score (MCS, Aus/HK) or SCCAI and UCEIS (UK). Results: Two hundred and ninety-three patients (53% male, median age 38 years, 196 Aus, 93 UK, 4 HK) were assessed with similar age, disease location and duration allowing combining of data. Median MCS pre VDZ was 8 (range 2–12, n = 152) and Mayo endoscopy subscore 2 of 3 (Aus, HK). Median SCCAI was 8 (range 0–13, n = 87) and UCEIS 5 of 8 (UK). VDZ was the first biological agent in 170 of 293 (58%), prior anti-TNF use occurred in 123 [reason for switching: primary non-response (PNR) n = 46, loss of response (LOR) n = 62, side-effects (SE) n = 15; two patients with side-effects were in remission and not included for analysis]. At VDZ start, 61% taking steroids and 56% immunomodulation (IM). Response rates at 3 months: 220 of 279 (79%) overall responded, TNF-naïve 134 of 163 (82%), TNF-exposed 86 of 116 (74% p = NS). Remission rates at 3 months: 155 of 279 (55%) in clinical remission, TNF-naïve 110 of 163 (67%), TNF-exposed 45 of 116 (39%, p = 0.01). 60 of 132 (45%) patients in remission were on IM and 49 of 101 (49%) if not (NS). Six months: Overall 144 of 235 (61%) in clinical remission, TNF-naïve 97 of 131 (74%), TNF-exposed 47 of 104 (45%, p = 0.03), and 60 of 124 (48%) in endoscopic remission (MES = 0 or 1). Steroids were ceased in 61 of 136 (45%) if in remission and 23 of 85 (27%) if not (p = 0.08). 39% (49 of 125) patients in remission were on IM and 29% (24 of 82) if not (NS). 12 months: Overall 117 of 196 (60%) were in remission, TNF-naïve 72 of 106 (68%), TNF-exposed 45 of 90 (50%, NS). No significant difference in remission rates seen between PNR, LOR, or anti-TNF naïve patients. Steroids ceased in 55 of 110 (50%) if in remission and 6 of 80 (8%) if not (p ≺ 0.001). Thirty-seven of 104 (36%) patients in remission were on IM and 13 of 78 (17%, p = 0.03) if not. Those in remission at 3 and 6 months, 90% (74 of 82) and 92% (96 of 104), respectively maintained remission. Smoking status did not affect response to VDZ. Colectomy occurred in 33 of 293 (11%). Adverse events occurred in 20 of 293 (7%); 2 were serious (Klebsiella sepsis and hemophagocytic syndrome). Conclusions: VDZ induced remission in 55% at 3 months and 61% at 6 months with >90% maintaining remission at 12 months. VDZ use continued for 12 months in 71% (139 of 196) with 61% in remission. Steroids were withdrawn in 50% patients in remission at 12 months. IMs might increase remission rates at 12 months. VDZ was initially more effective in anti-TNF naïve patients but differences were lost at 12 months suggesting patience may be needed in anti-TNF-exposed patients

P571 Vedolizumab (VDZ) real-world outcomes in ulcerative colitis (UC)

Background: In GEMINI 1, UC response to vedolizumab (VDZ) was 47% at Week 6 and 42% by Week 52. Our aim was to assess real-life outcomes for VDZ in UC. Methods: Data collected at 12 Australian (Aus), 1 UK and 2 Hong Kong (HK) centres, assessed response to VDZ at 3, 6, and 12 months using the Mayo Clinic Score (MCS, Aus/HK) or SCCAI and UCEIS (UK). Results: Two hundred and ninety-three patients (53% male, median age 38 years, 196 Aus, 93 UK, 4 HK) were assessed with similar age, disease location and duration allowing combining of data. Median MCS pre VDZ was 8 (range 2–12, n = 152) and Mayo endoscopy subscore 2 of 3 (Aus, HK). Median SCCAI was 8 (range 0–13, n = 87) and UCEIS 5 of 8 (UK). VDZ was the first biological agent in 170 of 293 (58%), prior anti-TNF use occurred in 123 [reason for switching: primary non-response (PNR) n = 46, loss of response (LOR) n = 62, side-effects (SE) n = 15; two patients with side-effects were in remission and not included for analysis]. At VDZ start, 61% taking steroids and 56% immunomodulation (IM). Response rates at 3 months: 220 of 279 (79%) overall responded, TNF-naïve 134 of 163 (82%), TNF-exposed 86 of 116 (74% p = NS). Remission rates at 3 months: 155 of 279 (55%) in clinical remission, TNF-naïve 110 of 163 (67%), TNF-exposed 45 of 116 (39%, p = 0.01). 60 of 132 (45%) patients in remission were on IM and 49 of 101 (49%) if not (NS). Six months: Overall 144 of 235 (61%) in clinical remission, TNF-naïve 97 of 131 (74%), TNF-exposed 47 of 104 (45%, p = 0.03), and 60 of 124 (48%) in endoscopic remission (MES = 0 or 1). Steroids were ceased in 61 of 136 (45%) if in remission and 23 of 85 (27%) if not (p = 0.08). 39% (49 of 125) patients in remission were on IM and 29% (24 of 82) if not (NS). 12 months: Overall 117 of 196 (60%) were in remission, TNF-naïve 72 of 106 (68%), TNF-exposed 45 of 90 (50%, NS). No significant difference in remission rates seen between PNR, LOR, or anti-TNF naïve patients. Steroids ceased in 55 of 110 (50%) if in remission and 6 of 80 (8%) if not (p ≺ 0.001). Thirty-seven of 104 (36%) patients in remission were on IM and 13 of 78 (17%, p = 0.03) if not. Those in remission at 3 and 6 months, 90% (74 of 82) and 92% (96 of 104), respectively maintained remission. Smoking status did not affect response to VDZ. Colectomy occurred in 33 of 293 (11%). Adverse events occurred in 20 of 293 (7%); 2 were serious (Klebsiella sepsis and hemophagocytic syndrome). Conclusions: VDZ induced remission in 55% at 3 months and 61% at 6 months with >90% maintaining remission at 12 months. VDZ use continued for 12 months in 71% (139 of 196) with 61% in remission. Steroids were withdrawn in 50% patients in remission at 12 months. IMs might increase remission rates at 12 months. VDZ was initially more effective in anti-TNF naïve patients but differences were lost at 12 months suggesting patience may be needed in anti-TNF-exposed patients

P571 Vedolizumab (VDZ) real-world outcomes in ulcerative colitis (UC)

Background: In GEMINI 1, UC response to vedolizumab (VDZ) was 47% at Week 6 and 42% by Week 52. Our aim was to assess real-life outcomes for VDZ in UC. Methods: Data collected at 12 Australian (Aus), 1 UK and 2 Hong Kong (HK) centres, assessed response to VDZ at 3, 6, and 12 months using the Mayo Clinic Score (MCS, Aus/HK) or SCCAI and UCEIS (UK). Results: Two hundred and ninety-three patients (53% male, median age 38 years, 196 Aus, 93 UK, 4 HK) were assessed with similar age, disease location and duration allowing combining of data. Median MCS pre VDZ was 8 (range 2–12, n = 152) and Mayo endoscopy subscore 2 of 3 (Aus, HK). Median SCCAI was 8 (range 0–13, n = 87) and UCEIS 5 of 8 (UK). VDZ was the first biological agent in 170 of 293 (58%), prior anti-TNF use occurred in 123 [reason for switching: primary non-response (PNR) n = 46, loss of response (LOR) n = 62, side-effects (SE) n = 15; two patients with side-effects were in remission and not included for analysis]. At VDZ start, 61% taking steroids and 56% immunomodulation (IM). Response rates at 3 months: 220 of 279 (79%) overall responded, TNF-naïve 134 of 163 (82%), TNF-exposed 86 of 116 (74% p = NS). Remission rates at 3 months: 155 of 279 (55%) in clinical remission, TNF-naïve 110 of 163 (67%), TNF-exposed 45 of 116 (39%, p = 0.01). 60 of 132 (45%) patients in remission were on IM and 49 of 101 (49%) if not (NS). Six months: Overall 144 of 235 (61%) in clinical remission, TNF-naïve 97 of 131 (74%), TNF-exposed 47 of 104 (45%, p = 0.03), and 60 of 124 (48%) in endoscopic remission (MES = 0 or 1). Steroids were ceased in 61 of 136 (45%) if in remission and 23 of 85 (27%) if not (p = 0.08). 39% (49 of 125) patients in remission were on IM and 29% (24 of 82) if not (NS). 12 months: Overall 117 of 196 (60%) were in remission, TNF-naïve 72 of 106 (68%), TNF-exposed 45 of 90 (50%, NS). No significant difference in remission rates seen between PNR, LOR, or anti-TNF naïve patients. Steroids ceased in 55 of 110 (50%) if in remission and 6 of 80 (8%) if not (p ≺ 0.001). Thirty-seven of 104 (36%) patients in remission were on IM and 13 of 78 (17%, p = 0.03) if not. Those in remission at 3 and 6 months, 90% (74 of 82) and 92% (96 of 104), respectively maintained remission. Smoking status did not affect response to VDZ. Colectomy occurred in 33 of 293 (11%). Adverse events occurred in 20 of 293 (7%); 2 were serious (Klebsiella sepsis and hemophagocytic syndrome). Conclusions: VDZ induced remission in 55% at 3 months and 61% at 6 months with >90% maintaining remission at 12 months. VDZ use continued for 12 months in 71% (139 of 196) with 61% in remission. Steroids were withdrawn in 50% patients in remission at 12 months. IMs might increase remission rates at 12 months. VDZ was initially more effective in anti-TNF naïve patients but differences were lost at 12 months suggesting patience may be needed in anti-TNF-exposed patients