| 1. |
- Alsubai, Khalid, et al.
(author)
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Qatar Exoplanet Survey : Qatar-3b, Qatar-4b, and Qatar-5b
- 2017
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In: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 153:4
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Journal article (peer-reviewed)abstract
- We report the discovery of Qatar-3b, Qatar-4b, and Qatar-5b, three new transiting planets identified by the Qatar Exoplanet Survey. The three planets belong to the hot Jupiter family, with orbital periods of P-Q3b = 2.50792 days, P-Q4b = 1.80539 days, and P-Q5b = 2.87923 days. Follow-up spectroscopic observations reveal the masses of the planets to be M-Q3b = 4.31 +/- 0.47 M-J, M-Q4b = 6.10 +/- 0.54 M-J, and M-Q5b = 4.32 +/- 0.18 M-J, while model fits to the transit light curves yield radii of R-Q3b = 1.096 +/- 0.14 RJ, R-Q4b = 1.135 +/- 0.11 R-J, and R-Q5b = 1.107 +/- 0.064 R-J. The host stars are low-mass main sequence stars with masses and radii M-Q3 = 1.145 +/- 0.064 M circle dot, M-Q4 = 0.896 +/- 0.048 M circle dot, M-Q5 = 1.128 +/- 0.056 M circle dot and R-Q3 = 1.272 +/- 0.14 R circle dot, R-Q4 = 0.849 +/- 0.063 R circle dot, and R-Q5 = 1.076 +/- 0.051 R circle dot for Qatar-3, 4, and 5 respectively. The V magnitudes of the three host stars are V-Q3 = 12.88, V-Q4 = 13.60, and V-Q5 = 12.82. All three new planets can be classified as heavy hot Jupiters (M > 4 M-J).
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| 2. |
- Becker-Dreps, Sylvia, et al.
(author)
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Etiology of Childhood Diarrhea After Rotavirus Vaccine Introduction A Prospective, Population-based Study in Nicaragua
- 2014
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In: The Pediatric Infectious Disease Journal. - : Lippincott, Williams andamp; Wilkins. - 0891-3668 .- 1532-0987. ; 33:11, s. 1156-1163
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Journal article (peer-reviewed)abstract
- Background: Nicaragua was the first developing nation to implement routine immunization with the pentavalent rotavirus vaccine (RV5). In this RV5-immunized population, understanding infectious etiologies of childhood diarrhea is necessary to direct diarrhea treatment and prevention efforts. Methods: We followed a population-based sample of children less than5 years in Leon, Nicaragua for diarrhea episodes through household visits. Information was obtained on RV5 history and sociodemographics. Stool samples collected during diarrhea episodes and among healthy children underwent laboratory analysis for viral, bacterial and parasitic enteropathogens. Detection frequency and incidence of each enteropathogen was calculated. Results: The 826 children in the cohort experienced 677 diarrhea episodes during 607.5 child-years of exposure time (1.1 episodes per child-year). At least 1 enteropathogen was detected among 61.1% of the 337 diarrheal stools collected. The most common enteropathogens among diarrheal stools were: norovirus (20.4%), sapovirus (16.6%), enteropathogenic Escherichia coli (11.3%), Entamoeba histolytica/dispar (8.3%), Giardia lamblia (8.0%) and enterotoxigenic E. coli (7.7%), with rotavirus detected among 5.3% of diarrheal stools. Enteropathogenic Escherichia coli and enterotoxigenic E. coli were frequently detected among stools from healthy children. Among children with diarrhea, norovirus was more commonly detected among younger children (less than2 years) and G. lamblia was more commonly detected among older children (2-4 years). The mean age of rotavirus detection was 34.6 months. Conclusions: In this Central American community after RV5 introduction, rotavirus was not commonly detected among children with diarrhea. Prevention and appropriate management of norovirus and sapovirus should be considered to further reduce the burden of diarrheal disease.
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| 3. |
- Bosmans, Kim, et al.
(author)
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Experiences of insecurity among non-standard workers across different welfare states : A qualitative cross-country study
- 2023
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In: Social Science and Medicine. - : Elsevier. - 0277-9536 .- 1873-5347. ; 327
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Journal article (peer-reviewed)abstract
- In recent decades, economic crises and political reforms focused on employment flexibilization have increased the use of non-standard employment (NSE). National political and economic contexts determine how employers interact with labour and how the state interacts with labour markets and manages social welfare policies. These factors influence the prevalence of NSE and the level of employment insecurity it creates, but the extent to which a country’s policy context mitigates the health influences of NSE is unclear. This study describes how workers experience insecurities created by NSE, and how this influences their health and well-being, in countries with different welfare states: Belgium, Canada, Chile, Spain, Sweden, and the United States. Interviews with 250 workers in NSE were analysed using a multiple-case study approach. Workers in all countries experienced multiple insecurities (e.g., income and employment insecurity) and relational tension with employers/clients, with negative health and well-being influences, in ways that were shaped by social inequalities (e.g., related to family support or immigration status). Welfare state differences were reflected in the level of workers’ exclusion from social protections, the time scale of their insecurity (threatening daily survival or longer-term life planning), and their ability to derive a sense of control from NSE. Workers in Belgium, Sweden, and Spain, countries with more generous welfare states, navigated these insecurities with greater success and with less influence on health and well-being. Findings contribute to our understanding of the health and well-being influences of NSE across different welfare regimes and suggest the need in all six countries for stronger state responses to NSE. Increased investment in universal and more equal rights and benefits in NSE could reduce the widening gap between standard and NSE.
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| 4. |
- Li, Xuexin, et al.
(author)
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The anti-leprosy drug clofazimine reduces polyQ toxicity through activation of PPARγ
- 2024
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In: EBioMedicine. - 2352-3964. ; 103
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Journal article (peer-reviewed)abstract
- Background: PolyQ diseases are autosomal dominant neurodegenerative disorders caused by the expansion of CAG repeats. While of slow progression, these diseases are ultimately fatal and lack effective therapies. Methods: A high-throughput chemical screen was conducted to identify drugs that lower the toxicity of a protein containing the first exon of Huntington's disease (HD) protein huntingtin (HTT) harbouring 94 glutamines (Htt-Q94). Candidate drugs were tested in a wide range of in vitro and in vivo models of polyQ toxicity. Findings: The chemical screen identified the anti-leprosy drug clofazimine as a hit, which was subsequently validated in several in vitro models. Computational analyses of transcriptional signatures revealed that the effect of clofazimine was due to the stimulation of mitochondrial biogenesis by peroxisome proliferator-activated receptor gamma (PPARγ). In agreement with this, clofazimine rescued mitochondrial dysfunction triggered by Htt-Q94 expression. Importantly, clofazimine also limited polyQ toxicity in developing zebrafish and neuron-specific worm models of polyQ disease. Interpretation: Our results support the potential of repurposing the antimicrobial drug clofazimine for the treatment of polyQ diseases. Funding: A full list of funding sources can be found in the acknowledgments section.
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| 5. |
- Tawil, Rabi, et al.
(author)
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Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial
- 2024
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In: Lancet Neurology. - : ELSEVIER SCIENCE INC. - 1474-4422 .- 1474-4465. ; 23:5, s. 477-486
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Journal article (peer-reviewed)abstract
- Background Facioscapulohumeral muscular dystrophy is a hereditary progressive myopathy caused by aberrant expression of the transcription factor DUX4 in skeletal muscle. No approved disease-modifying treatments are available for this disorder. We aimed to assess the safety and efficacy of losmapimod (a small molecule that inhibits p38 alpha MAPK, a regulator of DUX4 expression, and p38 beta MAPK) for the treatment of facioscapulohumeral muscular dystrophy. Methods We did a randomised, double-blind, placebo-controlled phase 2b trial at 17 neurology centres in Canada, France, Spain, and the USA. We included adults aged 18-65 years with type 1 facioscapulohumeral muscular dystrophy (ie, with loss of repression of DUX4 expression, as ascertained by genotyping), a Ricci clinical severity score of 2-4, and at least one skeletal muscle judged using MRI to be suitable for biopsy. Participants were randomly allocated (1:1) to either oral losmapimod (15 mg twice a day) or matching placebo for 48 weeks, via an interactive response technology system. The investigator, study staff, participants, sponsor, primary outcome assessors, and study monitor were masked to the treatment allocation until study closure. The primary endpoint was change from baseline to either week 16 or 36 in DUX4driven gene expression in skeletal muscle biopsy samples, as measured by quantitative RT-PCR. The primary efficacy analysis was done in all participants who were randomly assigned and who had available data for assessment, according to the modified intention-to-treat principle. Safety and tolerability were assessed as secondary endpoints. This study is registered at ClinicalTrials.gov, number NCT04003974. The phase 2b trial is complete; an open-label extension is ongoing. Findings Between Aug 27, 2019, and Feb 27, 2020, 80 people were enrolled. 40 were randomly allocated to losmapimod and 40 to placebo. 54 (68%) participants were male and 26 (33%) were female, 70 (88%) were White, and mean age was 45<middle dot>7 (SD 12<middle dot>5) years. Least squares mean changes from baseline in DUX4driven gene expression did not differ significantly between the losmapimod (0<middle dot>83 [SE 0<middle dot>61]) and placebo (0<middle dot>40 [0<middle dot>65]) groups (difference 0<middle dot>43 [SE 0<middle dot>56; 95% CI -1<middle dot>04 to 1<middle dot>89]; p=0<middle dot>56). Losmapimod was well tolerated. 29 treatment-emergent adverse events (nine drugrelated) were reported in the losmapimod group compared with 23 (two drug-related) in the placebo group. Two participants in the losmapimod group had serious adverse events that were deemed unrelated to losmapimod by the investigators (alcohol poisoning and suicide attempt; postoperative wound infection) compared with none in the placebo group. No treatment discontinuations due to adverse events occurred and no participants died during the study. Interpretation Although losmapimod did not significantly change DUX4-driven gene expression, it was associated with potential improvements in prespecified structural outcomes (muscle fat infiltration), functional outcomes (reachable workspace, a measure of shoulder girdle function), and patient-reported global impression of change compared with placebo. These findings have informed the design and choice of efficacy endpoints for a phase 3 study of losmapimod in adults with facioscapulohumeral muscular dystrophy.
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