| 1. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 2. |
- Akiyama, Kazunori, et al.
(författare)
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The persistent shadow of the supermassive black hole of M 87: I. Observations, calibration, imaging, and analysis*
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 681
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Tidskriftsartikel (refereegranskat)abstract
- In April 2019, the Event Horizon Telescope (EHT) Collaboration reported the first-ever event-horizon-scale images of a black hole, resolving the central compact radio source in the giant elliptical galaxy M 87. These images reveal a ring with a southerly brightness distribution and a diameter of ∼42 μas, consistent with the predicted size and shape of a shadow produced by the gravitationally lensed emission around a supermassive black hole. These results were obtained as part of the April 2017 EHT observation campaign, using a global very long baseline interferometric radio array operating at a wavelength of 1.3 mm. Here, we present results based on the second EHT observing campaign, taking place in April 2018 with an improved array, wider frequency coverage, and increased bandwidth. In particular, the additional baselines provided by the Greenland telescope improved the coverage of the array. Multiyear EHT observations provide independent snapshots of the horizon-scale emission, allowing us to confirm the persistence, size, and shape of the black hole shadow, and constrain the intrinsic structural variability of the accretion flow. We have confirmed the presence of an asymmetric ring structure, brighter in the southwest, with a median diameter of 43.3-3.1+1.5 μas. The diameter of the 2018 ring is remarkably consistent with the diameter obtained from the previous 2017 observations. On the other hand, the position angle of the brightness asymmetry in 2018 is shifted by about 30 relative to 2017. The perennial persistence of the ring and its diameter robustly support the interpretation that the ring is formed by lensed emission surrounding a Kerr black hole with a mass ∼6.5× 109M. The significant change in the ring brightness asymmetry implies a spin axis that is more consistent with the position angle of the large-scale jet.
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| 3. |
- Echiburu-Trujillo, Constanza, et al.
(författare)
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Chasing the Break: Tracing the Full Evolution of a Black Hole X-Ray Binary Jet with Multiwavelength Spectral Modeling
- 2024
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Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 962:2
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Tidskriftsartikel (refereegranskat)abstract
- Black hole (BH) X-ray binaries (XRBs) are ideal targets to study the connection between accretion inflow and jet outflow. Here we present quasi-simultaneous, multiwavelength observations of the Galactic BH system MAXI J1820+070, throughout its 2018-2019 outburst. Our data set includes coverage from the radio through X-ray bands from 17 different instruments/telescopes, and encompasses 19 epochs over a 7 month period, resulting in one of the most well-sampled multiwavelength data sets of a BH XRB outburst to date. With our data, we compile and model the broadband spectra of this source using a phenomenological model that includes emission from the jet, a companion star, and an accretion flow. This modeling allows us to track the evolution of the spectral break in the jet spectrum, a key observable that samples the jet launching region. We find that the spectral break location changes over at least approximate to 3 orders of magnitude in electromagnetic frequency over this period. Using these spectral break measurements, we link the full cycle of jet behavior, including the rising, quenching, and reignition, to the changing accretion flow properties as the source evolves through its different accretion states. Our analysis shows consistent jet behavior with other sources in similar phases of their outbursts, reinforcing the idea that jet quenching and recovery may be a global feature of BH XRB systems in outburst. Our results also provide valuable evidence supporting a close connection between the geometry of the inner accretion flow and the base of the jet.
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| 4. |
- Lipcsey, Miklós, et al.
(författare)
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Prævalens af delvis behandlet supralabial hirsutisme hos diktatorer
- 2012
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Ingår i: Ugeskrift for laeger. - 1603-6824. ; 174:49, s. 3078-3081
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION:This study investigated whether heads of state commonly regarded as dictators have a higher prevalence of partially treated supralabial hirsutism (PTSLH), commonly called a moustache, than non-dictatorial states. Design: retrospective observational study. Setting: the world political arena from 1901 to 2000. Participants: cohort of 139 dictators, 122 preceding political leaders in the respective countries, 122 succeeding political leaders also in the respective countries, as well as 76 Nobel peace prize laureates as controls. Interventions: none. Main outcome measures: the prevalence of PTSLH was 122 preceding political leaders.RESULTS: Of 139 dictators 49 (35%) demonstrated photographic evidence of PTSLH, while 85 (61%) did not. Of 48 preceding leaders 22 (46%) had PTSLH (p = 0.18 compared to dictators); of 33 following leaders ten (30%) had PTSLH (p = 0.59 compared to dictators). Finally of 78 Nobel peace prize laureates 31 (40%) had PTSLH (p = 0.47 compared to dictators).CONCLUSIONS: Most dictators did not have PTSLH. Moreover, the prevalence of PTSLH among dictators did not differ from controls. These data do not lend support to the commonly held notion that PTSLH is a predictor of a future dictatorial political career. Electorates the world over can now support political candidates with PTSLH without increased fear of becoming victims of a dictatorial system or having an increased risk of mortality after their ascent to power.
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| 5. |
- Marchant, Rob, et al.
(författare)
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Drivers and trajectories of land cover change in East Africa : Human and environmental interactions from 6000 years ago to present
- 2018
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Ingår i: Earth-Science Reviews. - : Elsevier. - 0012-8252 .- 1872-6828. ; 178, s. 322-378
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Tidskriftsartikel (refereegranskat)abstract
- East African landscapes today are the result of the cumulative effects of climate and land-use change over millennial timescales. In this review, we compile archaeological and palaeoenvironmental data from East Africa to document land-cover change, and environmental, subsistence and land-use transitions, over the past 6000 years. Throughout East Africa there have been a series of relatively rapid and high-magnitude environmental shifts characterised by changing hydrological budgets during the mid- to late Holocene. For example, pronounced environmental shifts that manifested as a marked change in the rainfall amount or seasonality and subsequent hydrological budget throughout East Africa occurred around 4000, 800 and 300 radiocarbon years before present (yr BP). The past 6000 years have also seen numerous shifts in human interactions with East African ecologies. From the mid-Holocene, land use has both diversified and increased exponentially, this has been associated with the arrival of new subsistence systems, crops, migrants and technologies, all giving rise to a sequence of significant phases of land-cover change. The first large-scale human influences began to occur around 4000 yr BP, associated with the introduction of domesticated livestock and the expansion of pastoral communities. The first widespread and intensive forest clearances were associated with the arrival of iron-using early farming communities around 2500 yr BP, particularly in productive and easily-cleared mid-altitudinal areas. Extensive and pervasive land-cover change has been associated with population growth, immigration and movement of people. The expansion of trading routes between the interior and the coast, starting around 1300 years ago and intensifying in the eighteenth and nineteenth centuries CE, was one such process. These caravan routes possibly acted as conduits for spreading New World crops such as maize (Zea mays), tobacco (Nicotiana spp.) and tomatoes (Solanum lycopersicum), although the processes and timings of their introductions remains poorly documented. The introduction of southeast Asian domesticates, especially banana (Musa spp.), rice (Oryza spp.), taro (Colocasia esculenta), and chicken (Gallus gallus), via transoceanic biological transfers around and across the Indian Ocean, from at least around 1300 yr BP, and potentially significantly earlier, also had profound social and ecological consequences across parts of the region. Through an interdisciplinary synthesis of information and metadatasets, we explore the different drivers and directions of changes in land-cover, and the associated environmental histories and interactions with various cultures, technologies, and subsistence strategies through time and across space in East Africa. This review suggests topics for targeted future research that focus on areas and/or time periods where our understanding of the interactions between people, the environment and land-cover change are most contentious and/or poorly resolved. The review also offers a perspective on how knowledge of regional land-use change can be used to inform and provide perspectives on contemporary issues such as climate and ecosystem change models, conservation strategies, and the achievement of nature-based solutions for development purposes.
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| 6. |
- May, Sally K., et al.
(författare)
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Survival, Social Cohesion and Rock Art : The Painted Hands of Western Arnhem Land, Australia
- 2020
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Ingår i: Cambridge Archaeological Journal. - : Cambridge University Press. - 0959-7743 .- 1474-0540. ; 30:3, s. 491-510
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Tidskriftsartikel (refereegranskat)abstract
- This paper explores the complex story of a particular style of rock art in western Arnhem Land known as 'Painted Hands'. Using new evidence from recent fieldwork, we present a definition for their style, distribution and place in the stylistic chronologies of this region. We argue these motifs played an important cultural role in Aboriginal society during the period of European settlement in the region. We explore the complex messages embedded in the design features of the Painted Hands, arguing that they are more than simply hand stencils or markers of individuality. We suggest that these figures represent stylized and intensely encoded motifs with the power to communicate a high level of personal, clan and ceremonial identity at a time when all aspects of Aboriginal cultural identity were under threat.
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| 7. |
- Price, David B., et al.
(författare)
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Fractional exhaled nitric oxide as a predictor of response to inhaled corticosteroids in patients with non-specific respiratory symptoms and insignificant bronchodilator reversibility : a randomised controlled trial
- 2018
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Ingår i: The Lancet Respiratory Medicine. - : ELSEVIER SCI LTD. - 2213-2600 .- 2213-2619. ; 6:1, s. 29-39
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic non-specific respiratory symptoms are difficult to manage. This trial aimed to evaluate the association between baseline fractional exhaled nitric oxide (FENO) and the response to inhaled corticosteroids in patients with non-specific respiratory symptoms.Methods: In this double-blind randomised placebo-controlled trial, we enrolled undiagnosed patients, aged 18-80 years, with cough, wheeze, or dyspnoea and less than 20% bronchodilator reversibility across 26 primary care centres and hospitals in the UK and Singapore. Patients were assessed for 2 weeks before being randomly assigned (1: 1) to 4 weeks of treatment with extrafine inhaled corticosteroids (QVAR 80 mu g, two puffs twice per day, equivalent to 800 mu g per day beclomethasone dipropionate) or placebo. Randomisation was stratified by baseline FENO measurement: normal (<= 25 parts per billion [ppb]), intermediate (>25 tp <40 ppb), and high (>= 40 ppb). The primary endpoint was change in Asthma Control Questionnaire (ACQ7) mean score. We used generalised linear modelling to assess FENO as a predictor of response, estimating an interaction effect between FENO and treatment on change in ACQ7. We did our primary and secondary analyses in the per-protocol set, which excluded patients with non-completion of the primary endpoint, non-compliance to treatment (ascertained by patient report), and study visits made outside the predefined visit windows. This study is registered on ClinicalTrials.gov, number NCT02294279.Findings: Between Feb 4, 2015, and July 12, 2016, we randomly assigned 294 patients to extrafine inhaled corticosteroid treatment (n=148) or placebo (n=146). Following exclusions due to protocol violations, we analysed 214 patients (114 extrafine inhaled corticosteroids and 100 placebo). We observed a significant interaction between baseline FENO and treatment group for every 10 ppb increase in baseline FENO, with the change in ACQ7 greater in the extrafine inhaled corticosteroids group than in the placebo group (difference between groups 0.071, 95% CI 0.002 to 0.139; p=0.044). The most common adverse events were nasopharyngitis (18 [12%] patients in the treatment group vs 13 [9%] in the placebo group), infections and infestations (25 [17%] vs 21 [14%]), and respiratory, thoracic, and mediastinal disorders (13 [9%] vs 17 [12%]).Interpretation: FENO measurement is an easy and non-invasive tool to use in clinical practice in patients with nonspecific respiratory symptoms to predict response to inhaled corticosteroids. Further research is needed to examine its role in patients with evidence of other airway diseases, such as chronic obstructive pulmonary disease.
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