Ruling Out Bosonic Repulsive Dark Matter in Thermal Equilibrium

Self-interacting dark matter (SIDM), especially bosonic, has been considered a promising candidate to replace cold dark matter (CDM) as it resolves some of the problems associated with CDM. Here, we rule out the possibility that dark matter is a repulsive boson in thermal equilibrium. We develop the model first proposed by Goodman (2000) and derive the equation of state at finite temperature. Isothermal spherical halo models indicate a Bose-Einstein condensed core surrounded by a non-degenerate envelope, with an abrupt density drop marking the boundary between the two phases. Comparing this feature with observed rotation curves constrains the interaction strength of our model's DM particle, and Bullet Cluster measurements constrain the scattering cross section. Both ultimately can be cast as constraints on the particle's mass. We find these two constraints cannot be satisfied simultaneously in any realistic halo model---and hence dark matter cannot be a repulsive boson in thermal equilibrium. It is still left open that DM may be a repulsive boson provided it is not in thermal equilibrium; this requires that the mass of the particle be significantly less than a millivolt.Comment: 13 pages, 3 figures, 1 table, accepted MNRAS August 9 201

Exploring the Akt/PI3 Kinase Signaling Pathway in the Avian Retina

The Akt pathway is an important cell-signaling pathway that can affect many cellular processes including growth and proliferation. This study aims to explore the role of the Akt pathway in the formation of Muller glia-derived progenitors in the avian retina. The results show that pS6 (a readout of the Akt pathway) is expressed in embryonic retina but there are minimal levels in a mature, normal retina. Upon excitotoxic damage or FGF2 stimulation, pS6 is highly upregulated with a peak at 4h after damage. Furthermore, VO-OHpic trihydrate (VOTH), a PTEN inhibitor was able to increase the number of proliferating Muller glia four fold. We conclude that the Akt pathway is not active in a normal retina, the Akt/mTOR pathway is rapidly activated in damaged retinas, and this pathway stimulates the formation of Muller glia-derived progenitors.No embargoAcademic Major: Molecular Genetic

Assessing the number of users who are excluded by domestic heating controls

This is the pre-print version of the Article. This Article is also referred to as: "Assessing the 'Design Exclusion' of Heating Controls at a Low-Cost, Low-Carbon Housing Development". - Copyright @ 2011 Taylor & FrancisSpace heating accounts for almost 60% of the energy delivered to housing which in turn accounts for nearly 27% of the total UK's carbon emissions. This study was conducted to investigate the influence of heating control design on the degree of ‘user exclusion’. This was calculated using the Design Exclusion Calculator, developed by the Engineering Design Centre at the University of Cambridge. To elucidate the capability requirements of the system, a detailed hierarchical task analysis was produced, due to the complexity of the overall task. The Exclusion Calculation found that the current design placed excessive demands upon the capabilities of at least 9.5% of the UK population over 16 years old, particularly in terms of ‘vision’, ‘thinking’ and ‘dexterity’ requirements. This increased to 20.7% for users over 60 years old. The method does not account for the level of numeracy and literacy and so the true exclusion may be higher. Usability testing was conducted to help validate the results which indicated that 66% of users at a low-carbon housing development could not programme their controls as desired. Therefore, more detailed analysis of the cognitive demands placed upon the users is required to understand where problems within the programming process occur. Further research focusing on this cognitive interaction will work towards a solution that may allow users to behave easily in a more sustainable manner

Long-Term Follow-Up of Children Treated With Peginterferon and Ribavirin for Hepatitis C Virus Infection

Objectives: The aim of the study was to describe the 5-year follow-up of children who received peginterferon and ribavirin in a global, open-label study. Methods: A 5-year follow-up study of 107 children and adolescents ages 3 to 17 years with chronic hepatitis C virus infection who received peginterferon and ribavirin for 24 or 48 weeks. No drugs were administered during follow-up. Results: Ninety-four patients were enrolled in the long-term follow-up portion of the study;the median duration of follow-up was 287 weeks (range, 73-339). Of 63 patients with sustained virologic response who were enrolled, 54 completed 5 years of follow-up;none had relapse in the 5-year follow-up period. Significant decreases in height z scores were observed during treatment. The effect of treatment on height z score was larger in patients treated for 48 weeks compared with those treated for 24 weeks (mean change from baseline to the end of treatment was -0.13 [P < 0.001] and -0.44 [P < 0.001] in the 247 and 48-week treatment groups, respectively). Among patients treated for 24 weeks, full recovery of height z scores to baseline was observed by 1 year of follow-up, whereas only partial recovery was observed during 5 years of follow-up in patients treated for 48 weeks (mean change from baseline to the final follow-up visit was -0.16 (P=NS) and 0.32 (P < 0.05) in the 24- and 48-week treatment groups, respectively). Similar patterns were observed for weight and body mass index z scores. Conclusions: Impairment of growth should be considered when assessing the risk-benefit profile of peginterferon/ribavirin therapy in children with hepatitis C virus infection. In deciding to treat children with chronic hepatitis C virus, considerations should include both deferring treatment in patients during optimal growth periods, and the possibility that interferon free regimens may be available to children in the next 5 to 10 years

Effects of red clover isoflavones on tall fescue seed fermentation and microbial populations \u3ci\u3ein vitro\u3c/i\u3e

Negative impacts of endophyte-infected Lolium arundinaceum (Darbyshire) (tall fescue) are responsible for over $2 billion in losses to livestock producers annually. While the influence of endophyte-infected tall fescue has been studied for decades, mitigation methods have not been clearly elucidated. Isoflavones found in Trifolium pratense (red clover) have been the subject of recent research regarding tall fescue toxicosis mitigation. Therefore, the aim of this study was to determine the effect of ergovaline and red clover isoflavones on rumen microbial populations, fiber degradation, and volatile fatty acids (VFA) in an in vitro system. Using a dose of 1.10 mg × L-1, endophyte-infected or endophyte-free tall fescue seed was added to ANKOM fiber bags with or without 2.19 mg of isoflavones in the form of a control, powder, or pulverized tablet, resulting in a 2 × 3 factorial arrangements of treatments. Measurements of pH, VFA, bacterial taxa, as well as the disappearance of neutral detergent fiber (aNDF), acid detergent fiber (ADF), and crude protein (CP) were taken after 48 h of incubation. aNDF disappearance values were significantly altered by seed type (P = 0.003) and isoflavone treatment (P = 0.005), and ADF disappearance values were significantly different in a seed × isoflavone treatment interaction (P ≤ 0.05). A seed × isoflavone treatment interaction was also observed with respect to CP disappearance (P ≤ 0.05). Eighteen bacterial taxa were significantly altered by seed × isoflavone treatment interaction groups (P ≤ 0.05), eight bacterial taxa were increased by isoflavones (P ≤ 0.05), and ten bacterial taxa were altered by seed type (P ≤ 0.05). Due to the beneficial effect of isoflavones on tall fescue seed fiber degradation, these compounds may be viable options for mitigating fescue toxicosis. Further research should be conducted to determine physiological implications as well as microbiological changes in vivo

Effects of Red Clover Isoflavones on Tall Fescue Seed Fermentation and Microbial Populations \u3cem\u3eIn Vitro\u3c/em\u3e

Negative impacts of endophyte-infected Lolium arundinaceum (Darbyshire) (tall fescue) are responsible for over $2 billion in losses to livestock producers annually. While the influence of endophyte-infected tall fescue has been studied for decades, mitigation methods have not been clearly elucidated. Isoflavones found in Trifolium pratense (red clover) have been the subject of recent research regarding tall fescue toxicosis mitigation. Therefore, the aim of this study was to determine the effect of ergovaline and red clover isoflavones on rumen microbial populations, fiber degradation, and volatile fatty acids (VFA) in an in vitro system. Using a dose of 1.10 mg × L-1, endophyte-infected or endophyte-free tall fescue seed was added to ANKOM fiber bags with or without 2.19 mg of isoflavones in the form of a control, powder, or pulverized tablet, resulting in a 2 × 3 factorial arrangements of treatments. Measurements of pH, VFA, bacterial taxa, as well as the disappearance of neutral detergent fiber (aNDF), acid detergent fiber (ADF), and crude protein (CP) were taken after 48 h of incubation. aNDF disappearance values were significantly altered by seed type (P = 0.003) and isoflavone treatment (P = 0.005), and ADF disappearance values were significantly different in a seed × isoflavone treatment interaction (P ≤ 0.05). A seed × isoflavone treatment interaction was also observed with respect to CP disappearance (P ≤ 0.05). Eighteen bacterial taxa were significantly altered by seed × isoflavone treatment interaction groups (P ≤ 0.05), eight bacterial taxa were increased by isoflavones (P ≤ 0.05), and ten bacterial taxa were altered by seed type (P ≤ 0.05). Due to the beneficial effect of isoflavones on tall fescue seed fiber degradation, these compounds may be viable options for mitigating fescue toxicosis. Further research should be conducted to determine physiological implications as well as microbiological changes in vivo

Primis : design of a pivotal, randomized, phase 3 study evaluating the safety and efficacy of the nonsteroidal farnesoid X receptor agonist cilofexor in noncirrhotic patients with primary sclerosing cholangitis

BackgroundPrimary sclerosing cholangitis (PSC) is a chronic progressive liver disease leading to biliary fibrosis and cirrhosis. Cilofexor is a nonsteroidal farnesoid X receptor agonist that demonstrated significant improvements in liver biochemistry and markers of cholestasis in patients with PSC in a phase 2 study. We describe here the rationale, design, and implementation of the phase 3 PRIMIS trial, the largest placebo-controlled trial in PSC.MethodsAdults with large-duct PSC without cirrhosis are randomized 2:1 to receive oral cilofexor 100 mg once daily or placebo for up to 96 weeks during the blinded phase. Patients completing the blinded phase are eligible to receive open-label cilofexor 100 mg daily for up to 96 weeks. The primary objective is to evaluate whether cilofexor reduces the risk of fibrosis progression compared with placebo. Liver biopsy is performed at screening and Week 96 of the blinded phase for histologic assessment of fibrosis. The primary endpoint-chosen in conjunction with guidance from the U.S. Food and Drug Administration-is the proportion of patients with >= 1-stage increase in fibrosis according to Ludwig histologic classification at week 96. Secondary objectives include evaluation of changes in liver biochemistry, serum bile acids, liver fibrosis assessed by noninvasive methods, health-related quality of life, and safety of cilofexor.ConclusionThe phase 3 PRIMIS study is the largest randomized, double-blind, placebo-controlled trial in PSC to date and will allow for robust evaluation of the efficacy and safety of cilofexor in noncirrhotic patients with large-duct PSC.Trial Registration: ClinicalTrials.gov NCT03890120; registered 26/03/2019.Peer reviewe

Interferon Alfa-2b Alone or in Combination with Ribavirin as Initial Treatment for Chronic Hepatitis C

BACKGROUND Only 15 to 20 percent of patients with chronic hepatitis C have a sustained virologic response to interferon therapy. We compared the efficacy and safety of recombinant interferon alfa-2b alone with those of a combination of interferon alfa-2b and ribavirin for the initial treatment of patients with chronic hepatitis C. METHODS We randomly assigned 912 patients with chronic hepatitis C to receive standard-dose interferon alfa-2b alone or in combination with ribavirin (1000 or 1200 mg orally per day, depending on body weight) for 24 or 48 weeks. Efficacy was assessed by measurements of serum hepatitis C virus (HCV) RNA and serum aminotransferases and by liver biopsy. RESULTS The rate of sustained virologic response (defined as an undetectable serum HCV RNA level 24 weeks after treatment was completed) was higher among patients who received combination therapy for either 24 weeks (70 of 228 patients, 31 percent) or 48 weeks (87 of 228 patients, 38 percent) than among patients who received interferon alone for either 24 weeks (13 of 231 patients, 6 percent) or 48 weeks (29 of 225 patients, 13 percent) (P CONCLUSIONS In patients with chronic hepatitis C, initial therapy with interferon and ribavirin was more effective than treatment with interferon alone