| 1. |
- Bower, Peter, et al.
(författare)
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Influence of initial severity of depression on effectiveness of low intensity interventions : meta-analysis of individual patient data
- 2013
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Ingår i: BMJ (Clinical Research Edition). - : BMJ Publishing Group: BMJ. - 0959-8138 .- 1756-1833. ; 346
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Tidskriftsartikel (refereegranskat)abstract
- Objective To assess how initial severity of depression affects the benefit derived from low intensity interventions for depression.Design Meta-analysis of individual patient data from 16 datasets comparing low intensity interventions with usual care.Setting Primary care and community settings.Participants 2470 patients with depression.Interventions Low intensity interventions for depression (such as guided self help by means of written materials and limited professional support, and internet delivered interventions).Main outcome measures Depression outcomes (measured with the Beck Depression Inventory or Center for Epidemiologic Studies Depression Scale), and the effect of initial depression severity on the effects of low intensity interventions.Results Although patients were referred for low intensity interventions, many had moderate to severe depression at baseline. We found a significant interaction between baseline severity and treatment effect (coefficient −0.1 (95% CI −0.19 to −0.002)), suggesting that patients who are more severely depressed at baseline demonstrate larger treatment effects than those who are less severely depressed. However, the magnitude of the interaction (equivalent to an additional drop of around one point on the Beck Depression Inventory for a one standard deviation increase in initial severity) was small and may not be clinically significant.Conclusions The data suggest that patients with more severe depression at baseline show at least as much clinical benefit from low intensity interventions as less severely depressed patients and could usefully be offered these interventions as part of a stepped care model.
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| 2. |
- Di, Li, et al.
(författare)
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Evidence-based approach to assess passive diffusion and carrier-mediated drug transport
- 2012
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 17:15-16, s. 905-912
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Forskningsöversikt (refereegranskat)abstract
- Evidence supporting the action of passive diffusion and carrier-mediated (CM) transport in drug bioavailability and disposition is discussed to refute the recently proposed theory that drug transport is CM-only and that new transporters will be discovered that possess transport characteristics ascribed to passive diffusion. Misconceptions and faulty speculations are addressed to provide reliable guidance on choosing appropriate tools for drug design and optimization.
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| 3. |
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| 4. |
- Mayer, Ludovic, et al.
(författare)
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Widespread Pesticide Distribution in the European Atmosphere Questions their Degradability in Air
- 2024
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Ingår i: Environmental Science and Technology. - 0013-936X. ; 58:7, s. 3342-3352
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Tidskriftsartikel (refereegranskat)abstract
- Risk assessment of pesticide impacts on remote ecosystems makes use of model-estimated degradation in air. Recent studies suggest these degradation rates to be overestimated, questioning current pesticide regulation. Here, we investigated the concentrations of 76 pesticides in Europe at 29 rural, coastal, mountain, and polar sites during the agricultural application season. Overall, 58 pesticides were observed in the European atmosphere. Low spatial variation of 7 pesticides suggests continental-scale atmospheric dispersal. Based on concentrations in free tropospheric air and at Arctic sites, 22 pesticides were identified to be prone to long-range atmospheric transport, which included 15 substances approved for agricultural use in Europe and 7 banned ones. Comparison between concentrations at remote sites and those found at pesticide source areas suggests long atmospheric lifetimes of atrazine, cyprodinil, spiroxamine, tebuconazole, terbuthylazine, and thiacloprid. In general, our findings suggest that atmospheric transport and persistence of pesticides have been underestimated and that their risk assessment needs to be improved.
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| 5. |
- Mendieta-Leiva, Glenda, et al.
(författare)
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EpIG-DB: A database of vascular epiphyte assemblages in the Neotropics
- 2020
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Ingår i: Journal of Vegetation Science. - : Wiley. - 1100-9233 .- 1654-1103. ; 31, s. 518-528
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Tidskriftsartikel (refereegranskat)abstract
- Vascular epiphytes are a diverse and conspicuous component of biodiversity in tropical and subtropical forests. Yet, the patterns and drivers of epiphyte assemblages are poorly studied in comparison with soil-rooted plants. Current knowledge about diversity patterns of epiphytes mainly stems from local studies or floristic inventories, but this information has not yet been integrated to allow a better understanding of large-scale distribution patterns. EpIG-DB, the first database on epiphyte assemblages at the continental scale, resulted from an exhaustive compilation of published and unpublished inventory data from the Neotropics. The current version of EpIG-DB consists of 463,196 individual epiphytes from 3,005 species, which were collected from a total of 18,148 relevés (host trees and ‘understory’ plots). EpIG-DB reports the occurrence of ‘true’ epiphytes, hemiepiphytes and nomadic vines, including information on their cover, abundance, frequency and biomass. Most records (97%) correspond to sampled host trees, 76% of them aggregated in forest plots. The data is stored in a TURBOVEG database using the most up-to-date checklist of vascular epiphytes. A total of 18 additional fields were created for the standardization of associated data commonly used in epiphyte ecology (e.g. by considering different sampling methods). EpIG-DB currently covers six major biomes across the whole latitudinal range of epiphytes in the Neotropics but welcomes data globally. This novel database provides, for the first time, unique biodiversity data on epiphytes for the Neotropics and unified guidelines for future collection of epiphyte data. EpIG-DB will allow exploration of new ways to study the community ecology and biogeography of vascular epiphytes.
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| 6. |
- Murray, Christopher J. L., et al.
(författare)
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Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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| 7. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 8. |
- Pie, Marcio R., et al.
(författare)
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Phylogenetic diversity and the structure of host-epiphyte interactions across the Neotropics
- 2023
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Ingår i: PeerJ. - 2167-8359. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the mechanisms driving community assembly has been a major focus of ecological research for nearly a century, yet little is known about these mechanisms in commensal communities, particularly with respect to their historical/evolutionary components. Here, we use a large-scale dataset of 4,440 vascular plant species to explore the relationship between the evolutionary distinctiveness (ED) (as measured by the’species evolutionary history’ (SEH)) of host species and the phylogenetic diversity (PD) of their associated epiphyte species. Although there was considerable variation across hosts and their associated epiphyte species, they were largely unrelated to host SEH. Our results mostly support the idea that the determinants of epiphyte colonization success might involve host characteristics that are unrelated to host SEH (e.g., architectural differences between hosts). While determinants of PD of epiphyte assemblages are poorly known, they do not appear to be related to the evolutionary history of host species. Instead, they might be better explained by neutral processes of colonization and extinction. However, the high level of phylogenetic signal in epiphyte PD (independent of SEH) suggests it might still be influenced by yet unrecognized evolutionary determinants. This study highlights how little is still known about the phylogenetic determinants of epiphyte communities.
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| 9. |
- Shribman, Samuel, et al.
(författare)
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Plasma Neurofilament Light as a Biomarker of Neurological Involvement in Wilson's Disease.
- 2021
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Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 1531-8257. ; 36:2, s. 503-508
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Tidskriftsartikel (refereegranskat)abstract
- Outcomes are unpredictable for neurological presentations of Wilson's disease (WD). Dosing regimens for chelation therapy vary and monitoring depends on copper indices, which do not reflect end-organ damage.To identify a biomarker for neurological involvement in WD.Neuronal and glial-specific proteins were measured in plasma samples from 40 patients and 38 age-matched controls. Patients were divided into neurological or hepatic presentations and those with recent neurological presentations or deterioration associated with non-adherence were subcategorized as having active neurological disease. Unified WD Rating Scale scores and copper indices were recorded.Unlike copper indices, neurofilament light (NfL) concentrations were higher in neurological than hepatic presentations. They were also higher in those with active neurological disease when controlling for severity and correlated with neurological examination subscores in stable patients.NfL is a biomarker of neurological involvement with potential use in guiding chelation therapy and clinical trials for novel treatments. © 2020 University College London. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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| 10. |
- Smith, Dennis, et al.
(författare)
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Passive Lipoidal Diffusion and Carrier-Mediated Cell Uptake Are Both Important Mechanisms of Membrane Permeation in Drug Disposition
- 2014
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 11:6, s. 1727-1738
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Forskningsöversikt (refereegranskat)abstract
- Recently, it has been proposed that drug permeation is essentially carrier-mediated only and that passive lipoidal diffusion is negligible. This opposes the prevailing hypothesis of drug permeation through biological membranes, which integrates the contribution of multiple permeation mechanisms, including both carrier-mediated and passive lipoidal diffusion, depending on the compound's properties, membrane properties, and solution properties. The prevailing hypothesis of drug permeation continues to be successful for application and prediction in drug development. Proponents of the carrier-mediated only concept argue against passive lipoidal diffusion. However, the arguments are not supported by broad pharmaceutics literature. The carrier-mediated only concept lacks substantial supporting evidence and successful applications in drug development.
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