| 1. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 4. |
- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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| 5. |
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| 9. |
- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 10. |
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| 11. |
- Simon, C., et al.
(författare)
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Quantum memories
- 2010
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Ingår i: European Physical Journal D. Atomic, Molecular, Optical and Plasma Physics. - : Springer Science and Business Media LLC. - 1434-6060. ; 58:1, s. 1-22
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Tidskriftsartikel (refereegranskat)abstract
- We perform a review of various approaches to the implementation of quantum memories, with an emphasis on activities within the quantum memory sub-project of the EU integrated project "Qubit Applications". We begin with a brief overview over different applications for quantum memories and different types of quantum memories. We discuss the most important criteria for assessing quantum memory performance and the most important physical requirements. Then we review the different approaches represented in "Qubit Applications" in some detail. They include solid-state atomic ensembles, NV centers, quantum dots, single atoms, atomic gases and optical phonons in diamond. We compare the different approaches using the discussed criteria.
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| 12. |
- Antinori, A., et al.
(författare)
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Updated research nosology for HIV-associated neurocognitive disorders
- 2007
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Ingår i: Neurology. ; 69:18, s. 1789-99
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Tidskriftsartikel (refereegranskat)abstract
- In 1991, the AIDS Task Force of the American Academy of Neurology published nomenclature and research case definitions to guide the diagnosis of neurologic manifestations of HIV-1 infection. Now, 16 years later, the National Institute of Mental Health and the National Institute of Neurological Diseases and Stroke have charged a working group to critically review the adequacy and utility of these definitional criteria and to identify aspects that require updating. This report represents a majority view, and unanimity was not reached on all points. It reviews our collective experience with HIV-associated neurocognitive disorders (HAND), particularly since the advent of highly active antiretroviral treatment, and their definitional criteria; discusses the impact of comorbidities; and suggests inclusion of the term asymptomatic neurocognitive impairment to categorize individuals with subclinical impairment. An algorithm is proposed to assist in standardized diagnostic classification of HAND.
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| 13. |
- Buker, P., et al.
(författare)
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DO3SE modelling of soil moisture to determine ozone flux to forest trees
- 2012
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 12:12, s. 5537-5562
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Tidskriftsartikel (refereegranskat)abstract
- The DO3SE (Deposition of O-3 for Stomatal Exchange) model is an established tool for estimating ozone (O-3) deposition, stomatal flux and impacts to a variety of vegetation types across Europe. It has been embedded within the EMEP (European Monitoring and Evaluation Programme) photochemical model to provide a policy tool capable of relating the flux-based risk of vegetation damage to O-3 precursor emission scenarios for use in policy formulation. A key limitation of regional flux-based risk assessments has been the assumption that soil water deficits are not limiting O-3 flux due to the unavailability of evaluated methods for modelling soil water deficits and their influence on stomatal conductance (g(sto)), and subsequent O-3 flux. This paper describes the development and evaluation of a method to estimate soil moisture status and its influence on g(sto) for a variety of forest tree species. This DO3SE soil moisture module uses the Penman-Monteith energy balance method to drive water cycling through the soil-plant-atmosphere system and empirical data describing g(sto) relationships with pre-dawn leaf water status to estimate the biological control of transpiration. We trial four different methods to estimate this biological control of the transpiration stream, which vary from simple methods that relate soil water content or potential directly to g(sto), to more complex methods that incorporate hydraulic resistance and plant capacitance that control water flow through the plant system. These methods are evaluated against field data describing a variety of soil water variables, g(sto) and transpiration data for Norway spruce (Picea abies), Scots pine (Pinus sylvestris), birch (Betula pendula), aspen (Populus tremuloides), beech (Fagus sylvatica) and holm oak (Quercus ilex) collected from ten sites across Europe and North America. Modelled estimates of these variables show consistency with observed data when applying the simple empirical methods, with the timing and magnitude of soil drying events being captured well across all sites and reductions in transpiration with the onset of drought being predicted with reasonable accuracy. The more complex methods, which incorporate hydraulic resistance and plant capacitance, perform less well, with predicted drying cycles consistently underestimating the rate and magnitude of water loss from the soil. A sensitivity analysis showed that model performance was strongly dependent upon the local parameterisation of key model drivers such as the maximum g(sto), soil texture, root depth and leaf area index. The results suggest that the simple modelling methods that relate g(sto) directly to soil water content and potential provide adequate estimates of soil moisture and influence on g(sto) such that they are suitable to be used to assess the potential risk posed by O-3 to forest trees across Europe.
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| 14. |
- Hellerud, B. C., et al.
(författare)
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Combined inhibition of C5 and CD14 efficiently attenuated the inflammatory response in a porcine model of meningococcal sepsis
- 2017
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Ingår i: Journal of Intensive Care. - : Springer Science and Business Media LLC. - 2052-0492. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fulminant meningococcal sepsis, characterized by overwhelming innate immune activation, mostly affects young people and causes high mortality. This study aimed to investigate the effect of targeting two key molecules of innate immunity, complement component C5, and co-receptor CD14 in the Toll-like receptor system, on the inflammatory response in meningococcal sepsis. Methods: Meningococcal sepsis was simulated by continuous intravenous infusion of an escalating dose of heat-inactivated Neisseria meningitidis administered over 3 h. The piglets were randomized, blinded to the investigators, to a positive control group (n = 12) receiving saline and to an interventional group (n = 12) receiving a recombinant anti-CD14 monoclonal antibody together with the C5 inhibitor coversin. Results: A substantial increase in plasma complement activation in the untreated group was completely abolished in the treatment group (p = 0.006). The following inflammatory mediators were substantially reduced in plasma in the treatment group: Interferon-gamma by 75% (p = 0.0001), tumor necrosis factor by 50% (p = 0.01), Interleukin (IL)-8 by 50% (p = 0.03), IL-10 by 40% (p = 0.04), IL-12p40 by 50% (p = 0.03), and granulocyte CD11b (CR3) expression by 20% (p = 0.01). Conclusion: Inhibition of C5 and CD14 may be beneficial in attenuating the detrimental effects of complement activation and modulating the cytokine storm in patients with fulminant meningococcal sepsis.
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| 15. |
- Huber-Lang, Markus, et al.
(författare)
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Double blockade of CD14 and complement C5 abolishes the cytokine storm and improves morbidity and survival in polymicrobial sepsis in mice.
- 2014
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 192:11, s. 5324-5331
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Tidskriftsartikel (refereegranskat)abstract
- Sepsis and septic shock, caused by an excessive systemic host-inflammatory response, are associated with high morbidity and mortality. The complement system and TLRs provide important pattern recognition receptors initiating the cytokine storm by extensive cross-talk. We hypothesized that double blockade of complement C5 and the TLR coreceptor CD14 could improve survival of experimental polymicrobial sepsis. Mice undergoing cecal ligation and puncture (CLP)-induced sepsis were treated with neutralizing anti-CD14 Ab biG 53, complement C5 inhibitor coversin (Ornithodoros moubata C inhibitor), or a combination thereof. The inflammatory study (24-h observation) revealed statistically significant increases in 22 of 24 measured plasma biomarkers in the untreated CLP group, comprising 14 pro- and anti-inflammatory cytokines and 8 chemokines, growth factors, and granulocyte activation markers. Single CD14 or C5 blockade significantly inhibited 20 and 19 of the 22 biomarkers, respectively. Combined CD14 and C5 inhibition significantly reduced all 22 biomarkers (mean reduction 85%; range 54-95%) compared with the untreated CLP group. Double blockade was more potent than single treatment and was required to significantly inhibit IL-6 and CXCL1. Combined inhibition significantly reduced morbidity (motility and eyelid movement) and mortality measured over 10 d. In the positive control CLP group, median survival was 36 h (range 24-48 h). Combined treatment increased median survival to 96 h (range 24-240 h) (p = 0.001), whereas survival in the single-treatment groups was not significantly increased (median and range for anti-CD14 and anti-C5 treatment were 36 h [24-48 h] and 48 h [24-96 h]). Combined with standard intervention therapy, specific blockade of CD14 and C5 might represent a promising new therapeutic strategy for treatment of polymicrobial sepsis.
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| 16. |
- Kamali, Anatoli, et al.
(författare)
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A community randomized controlled trial to investigate impact of improved STD management and behavioural interventions on HIV incidence in rural Masaka, Uganda : trial design, methods and baseline findings
- 2002
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Ingår i: Tropical medicine & international health. - : Wiley. - 1360-2276 .- 1365-3156. ; 7:12, s. 1053-1063
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To describe study design, methods and baseline findings of a behavioural intervention alone and in combination with improved management of sexually transmitted diseases (STDs) aimed at reducing HIV incidence and other STDs. DESIGN: A three-arm community randomized controlled trial (RCT) of 18 rural communities (approximately 96 000 adults) in SW Uganda. A standardized behavioural intervention was implemented in 12 communities (arms A and B) through community-based education, meetings and information leaflets. Six of these communities in addition received improved STD management through government and private health units (arm B). Arm C communities received routine government health services. Impact assessment was through three questionnaire and serological surveys of 750-1000 adults in each community at 18-24-month intervals. The primary outcome measure was HIV incidence and secondary measures were syphilis and herpes simplex virus type 2 incidence, prevalence of Neisseria gonorrhoea and Chlamydia trachomatis and sexual behaviour changes. RESULTS: Approximately 15 000 adults (72% of eligible population) were enrolled at baseline. HIV baseline prevalence rates were 9-10% in all arms and demographic and behavioural characteristics and STD prevalence were also similar. In intervention communities, there were 391 995 attendance at 81 502 activities (6.1 per target adult), 164 063 leaflets distributed (2.6 per person) and 1 586 270 condoms (16.5 condoms per adult). In the STD communities a total of 12 239 STD cases (65% women) were seen over a 5-year period (7.7 per 100 adults/year). CONCLUSION: This is the first community RCT of its type with a behavioural component. There is fair baseline comparability between study arms and process data suggest that interventions were adequately implemented.
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| 17. |
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| 18. |
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| 19. |
- Lindenfors, Patrik, et al.
(författare)
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Primate brain architecture and selection in relation to sex
- 2007
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Ingår i: BMC Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 5:20
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Tidskriftsartikel (refereegranskat)abstract
- Background: Social and competitive demands often differ between the sexes in mammals. These differing demands should be expected to produce variation in the relative sizes of various brain structures. Sexual selection on males can be predicted to influence brain components handling sensory-motor skills that are important for physical competition or neural pathways involving aggression. Conversely, because female fitness is more closely linked to ecological factors and social interactions that enable better acquisition of resources, social selection on females should select for brain components important for navigating social networks. Sexual and social selection acting on one sex could produce sexual dimorphism in brain structures, which would result in larger species averages for those same brain structures. Alternatively, sex-specific selection pressures could produce correlated effects in the other sex, resulting in larger brain structures for both males and females of a species. Data are presently unavailable for the sex-specific sizes of brain structures for anthropoid primates, but under either scenario, the effects of sexual and social selection should leave a detectable signal in average sizes of brain structures for different species. Results: The degree of male intra-sexual selection was positively correlated with several structures involved in autonomic functions and sensory-motor skills, and in pathways relating to aggression and aggression control. The degree of male intra-sexual selection was not correlated with relative neocortex size, which instead was significantly positively correlated with female social group size, but negatively correlated with male group size. Conclusion: Sexual selection on males and social selection on females have exerted different effects on primate brain architecture. Species with a higher degree of male intra-sexual selection carry a neural signature of an evolutionary history centered on physical conflicts, but no traces of increased demands on sociocognitive tasks. Conversely, female sociality is indicated to have driven the evolution of socio-cognitive skills. Primate brain architecture is therefore likely to be a product of ecological and species-specific social factors as well as different sex-specific selection pressures. Our results also highlight the need for acquisition and analysis of sex-specific brain components in mammals.
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| 20. |
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| 21. |
- Nunn, A. D. G., et al.
(författare)
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The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Dietary overload of toxic, free metabolic intermediates leads to disrupted insulin signalling and fatty liver disease. However, it was recently reported that this pathway might not be universal: depletion of histone deacetylase (HDAC) enhances insulin sensitivity alongside hepatic lipid accumulation in mice, but the mechanistic role of microscopic lipid structure in this effect remains unclear. Here we study the effect of Entinostat, a synthetic HDAC inhibitor undergoing clinical trials, on hepatic lipid metabolism in the paradigmatic HepaRG liver cell line. Specifically, we statistically quantify lipid droplet morphology at single cell level utilizing label-free microscopy, coherent anti-Stokes Raman scattering, supported by gene expression. We observe Entinostat efficiently rerouting carbohydrates and free-fatty acids into lipid droplets, upregulating lipid coat protein gene Plin4, and relocating droplets nearer to the nucleus. Our results demonstrate the power of Entinostat to promote lipid synthesis and storage, allowing reduced systemic sugar levels and sequestration of toxic metabolites within protected protein-coated droplets, suggesting a potential therapeutic strategy for diseases such as diabetes and metabolic syndrome.
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| 22. |
- Palmer, Elizabeth E., et al.
(författare)
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Functional and clinical studies reveal pathophysiological complexity of CLCN4-related neurodevelopmental condition
- 2023
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Ingår i: Molecular Psychiatry. - : SPRINGERNATURE. - 1359-4184 .- 1476-5578. ; 28:2, s. 668-697
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Tidskriftsartikel (refereegranskat)abstract
- Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a "shift" of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis.
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| 23. |
- Singer, Andrew C, et al.
(författare)
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Meeting Report : Risk Assessment of Tamiflu Use Under Pandemic Conditions
- 2008
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Ingår i: Environmental Health Perspectives. ; 116:11, s. 1563-7
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Tidskriftsartikel (refereegranskat)abstract
- On 3 October 2007, 40 participants with diverse expertise attended the workshop Tamiflu and the Environment: Implications of Use under Pandemic Conditions to assess the potential human health impact and environmental hazards associated with use of Tamiflu during an influenza pandemic. Based on the identification and risk-ranking of knowledge gaps, the consensus was that oseltamivir ethylester-phosphate (OE-P) and oseltamivir carboxylate (OC) were unlikely to pose an ecotoxicologic hazard to freshwater organisms. OC in river water might hasten the generation of OC-resistance in wildfowl, but this possibility seems less likely than the potential disruption that could be posed by OC and other pharmaceuticals to the operation of sewage treatment plants. The workgroup members agreed on the following research priorities: a) available data on the ecotoxicology of OE-P and OC should be published ; b) risk should be assessed for OC-contaminated river water generating OC-resistant viruses in wildfowl ; c) sewage treatment plant functioning due to microbial inhibition by neuraminidase inhibitors and other antimicrobials used during a pandemic should be investigated ; and d) realistic worst-case exposure scenarios should be developed. Additional modeling would be useful to identify localized areas within river catchments that might be prone to high pharmaceutical concentrations in sewage treatment plant effluent. Ongoing seasonal use of Tamiflu in Japan offers opportunities for researchers to assess how much OC enters and persists in the aquatic environment.
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