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

A Repeated Measures Experiment of Green Exercise to Improve Self-Esteem in UK School Children

Exercising in natural, green environments creates greater improvements in adult's self-esteem than exercise undertaken in urban or indoor settings. No comparable data are available for children. The aim of this study was to determine whether so called 'green exercise' affected changes in self-esteem; enjoyment and perceived exertion in children differently to urban exercise. We assessed cardiorespiratory fitness (20 m shuttle-run) and self-reported physical activity (PAQ-A) in 11 and 12 year olds (n = 75). Each pupil completed two 1.5 mile timed runs, one in an urban and another in a rural environment. Trials were completed one week apart during scheduled physical education lessons allocated using a repeated measures design. Self-esteem was measured before and after each trial, ratings of perceived exertion (RPE) and enjoyment were assessed after completing each trial. We found a significant main effect (F (1,74), = 12.2, p<0.001), for the increase in self-esteem following exercise but there was no condition by exercise interaction (F (1,74), = 0.13, p = 0.72). There were no significant differences in perceived exertion or enjoyment between conditions. There was a negative correlation (r = -0.26, p = 0.04) between habitual physical activity and RPE during the control condition, which was not evident in the green exercise condition (r = -0.07, p = 0.55). Contrary to previous studies in adults, green exercise did not produce significantly greater increases in self-esteem than the urban exercise condition. Green exercise was enjoyed more equally by children with differing levels of habitual physical activity and has the potential to engage less active children in exercise. © 2013 Reed et al

Submillimetre Transient Science in the Next Decade

White paper from the EAO Submillimetre Futures Meeting, 20-23 May 2019, Nanjing, ChinaThis white paper gives a brief summary of the time domain science that has been performed with the JCMT in recent years and highlights the opportunities for continuing work in this field over the next decade. The main focus of this document is the JCMT Transient Survey, a large program initiated in 2015 to measure the frequency and amplitude of variability events associated with protostars in nearby star-forming regions. After summarising the major accomplishments so far, an outline is given for extensions to the current survey, featuring a discussion on what will be possible with the new 850 micron camera that is expected to be installed in late 2022. We also discuss possible applications of submillimetre monitoring to active galactic nuclei, X-ray binaries, asymptotic giant branch stars, and flare stars.Science and Technology Facilities Counci

Hepatic safety and efficacy of immunomodulatory drugs used in patients with autoimmune hepatitis.

BACKGROUND AND AIMS There is little data on the hepatic efficacy and safety of immunomodulatory drugs used in patients with autoimmune hepatitis (AIH), despite their established use in dermatology, rheumatology and inflammatory bowel diseases (IBD). Our aim was to collect real-life data on the experience of expert centres in treating AIH patients with these drugs, considered unconventional for AIH management. METHODS Online survey among hepatology centres being part of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). RESULTS 25 AIH patients have been reported. Ten were female, median age at diagnosis was 28 years; median follow-up was 17 months. All had initially received AIH-standard treatment. AIH-unconventional treatment was initiated for concomitant autoimmune diseases in 15 cases: nine for IBD (five vedolizumab and four ustekinumab), and one each for following diseases: autoinflammatory syndrome (tocilizumab), chronic urticaria (omalizumab), rheumatoid arthritis (abatacept), psoriasis (guselkumab), psoriatric arthritis (secukinumab, followed by ustekinumab) and alopecia (ruxolitinib). Three patients were treated with immunomodulatory drugs for side effects of previous treatments, including two patients with IBD treated with vedolizumab and ustekinumab, respectively, and one treated with belimumab. At the end of follow-up, 13 patients were in complete biochemical response, the patient on omalizumab had a relapse, and four patients with concomitant IBD had insufficient response. Seven patients were treated for lack of biochemical remission, of whom six with belimumab, all initially reaching complete biochemical response, but five relapsing during follow-up; and one with secukinumab, having concomitant rheumatoid arthritis and ankylosing spondylitis, reaching complete biochemical response. Only the patient on abatacept received unconventional treatment as monotherapy. Side effects were reported in two patients on belimumab: one recurrent soft tissue infections, one fatigue and arthralgia. CONCLUSION Among 25 AIH patients who were treated with immunomodulatory drugs for different reasons, the majority had a fovorable course, relapse was frequent in difficult-to-treat patients who received belimumab, and four with concomitant IBD had insufficient response

Triterpenoid saponins from the root bark of haplocoelum congolanum

peer reviewedTwo undescribed triterpenoid saponins together with 5 known ones were isolated from the root bark of Haplocoelum congolanum Hauman. Their structures were elucidated by spectroscopic methods including one-dimensional and two-dimensional nuclear magnetic resonance experiments in combination with mass spectrometry as 3-O-(4-O-[3-hydroxy-3-methylglutaryl])-α-l-arabinopyranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-[β-d-glucopyranosyl-(1→4)]-α-l-arabinopyranosyloleanolic acid and 3-O-α-l-arabinofuranosyl-(1→3)-α-l-rhamnopyranosyl-(1→2)-[β-d-glucopyranosyl-(1→4)]-α-l-arabinopyranosyloleanolic acid. © The Author(s) 201

Cross-National Differences in Victimization : Disentangling the Impact of Composition and Context

Varying rates of criminal victimization across countries are assumed to be the outcome of countrylevel structural constraints that determine the supply ofmotivated o¡enders, as well as the differential composition within countries of suitable targets and capable guardianship. However, previous empirical tests of these ‘compositional’ and ‘contextual’ explanations of cross-national di¡erences have been performed upon macro-level crime data due to the unavailability of comparable individual-level data across countries. This limitation has had two important consequences for cross-national crime research. First, micro-/meso-level mechanisms underlying cross-national differences cannot be truly inferred from macro-level data. Secondly, the e¡ects of contextual measures (e.g. income inequality) on crime are uncontrolled for compositional heterogeneity. In this paper, these limitations are overcome by analysing individual-level victimization data across 18 countries from the International CrimeVictims Survey. Results from multi-level analyses on theft and violent victimization indicate that the national level of income inequality is positively related to risk, independent of compositional (i.e. micro- and meso-level) di¡erences. Furthermore, crossnational variation in victimization rates is not only shaped by di¡erences in national context, but also by varying composition. More speci¢cally, countries had higher crime rates the more they consisted of urban residents and regions with lowaverage social cohesion.

Hedonic Taste in Drosophila Revealed by Olfactory Receptors Expressed in Taste Neurons

Taste and olfaction are each tuned to a unique set of chemicals in the outside world, and their corresponding sensory spaces are mapped in different areas in the brain. This dichotomy matches categories of receptors detecting molecules either in the gaseous or in the liquid phase in terrestrial animals. However, in Drosophila olfactory and gustatory neurons express receptors which belong to the same family of 7-transmembrane domain proteins. Striking overlaps exist in their sequence structure and in their expression pattern, suggesting that there might be some functional commonalities between them. In this work, we tested the assumption that Drosophila olfactory receptor proteins are compatible with taste neurons by ectopically expressing an olfactory receptor (OR22a and OR83b) for which ligands are known. Using electrophysiological recordings, we show that the transformed taste neurons are excited by odor ligands as by their cognate tastants. The wiring of these neurons to the brain seems unchanged and no additional connections to the antennal lobe were detected. The odor ligands detected by the olfactory receptor acquire a new hedonic value, inducing appetitive or aversive behaviors depending on the categories of taste neurons in which they are expressed i.e. sugar- or bitter-sensing cells expressing either Gr5a or Gr66a receptors. Taste neurons expressing ectopic olfactory receptors can sense odors at close range either in the aerial phase or by contact, in a lipophilic phase. The responses of the transformed taste neurons to the odorant are similar to those obtained with tastants. The hedonic value attributed to tastants is directly linked to the taste neurons in which their receptors are expressed