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  • 2021
  • swepub:Mat__t
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  • Cossarizza, A., et al. (author)
  • Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
  • 2019
  • In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
  • Journal article (peer-reviewed)abstract
    • These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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  • Thoma, B, et al. (author)
  • An international, interprofessional investigation of the self-reported podcast listening habits of emergency clinicians: A METRIQ Study
  • 2020
  • In: CJEM. - : Springer Science and Business Media LLC. - 1481-8043 .- 1481-8035. ; 22:1, s. 112-117
  • Journal article (peer-reviewed)abstract
    • ObjectivesPodcasts are increasingly being used for medical education. A deeper understanding of usage patterns would inform both producers and researchers of medical podcasts. We aimed to determine how and why podcasts are used by emergency medicine and critical care clinicians.MethodsAn international interprofessional sample (medical students, residents, physicians, nurses, physician assistants, and paramedics) was recruited through direct contact and a multimodal social media (Twitter and Facebook) campaign. Each participant completed a survey outlining how and why they utilize medical podcasts. Recruitment materials included an infographic and study website.Results390 participants from 33 countries and 4 professions (medicine, nursing, paramedicine, physician assistant) completed the survey. Participants most frequently listened to medical podcasts to review new literature (75.8%), learn core material (75.1%), and refresh memory (71.8%). The majority (62.6%) were aware of the ability to listen at increased speeds, but most (76.9%) listened at 1.0 x (normal) speed. All but 25 (6.4%) participants concurrently performed other tasks while listening. Driving (72.3%), exercising (39.7%), and completing chores (39.2%) were the most common. A minority of participants used active learning techniques such as pausing, rewinding, and replaying segments of the podcast. Very few listened to podcasts multiple times.ConclusionsAn international cohort of emergency clinicians use medical podcasts predominantly for learning. Their listening habits (rarely employing active learning strategies and frequently performing concurrent tasks) may not support this goal. Further exploration of the impact of these activities on learning from podcasts is warranted.
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  • Creighton, S, et al. (author)
  • Predictive, pre-natal and diagnostic genetic testing for Huntington's disease : the experience in Canada from 1987 to 2000.
  • 2003
  • In: Clinical Genetics. - 0009-9163 .- 1399-0004. ; 63:6, s. 462-75
  • Journal article (peer-reviewed)abstract
    • Predictive and pre-natal testing for Huntington's Disease (HD) has been available since 1987. Initially this was offered by linkage analysis, which was surpassed by the advent of the direct mutation test for HD in 1993. Direct mutation analysis provided an accurate test that not only enhanced predictive and pre-natal testing, but also permitted the diagnostic testing of symptomatic individuals. The objective of this study was to investigate the uptake, utilization, and outcome of predictive, pre-natal and diagnostic testing in Canada from 1987 to April 1, 2000. A retrospective design was used; all Canadian medical genetics centres and their affiliated laboratories offering genetic testing for HD were invited to participate. A total of 15 of 22 centres (68.2%), currently offering or ever having offered genetic testing for HD, responded, providing data on test results, demographics, and clinical history. A total of 1061 predictive tests, 15 pre-natal tests, and 626 diagnostic tests were performed. The uptake for predictive testing was approximately 18% of the estimated at-risk Canadian population, ranging from 12.5% in the Maritimes to 20.7% in British Columbia. There appears to have been a decline in the rate of testing in recent years. Of the predictive tests, 45.0% of individuals were found to have an increased risk, and a preponderance of females (60.2%) sought testing. A greater proportion of those at < or = 25% risk sought predictive testing once direct CAG mutation analysis had become available (10.9% after mutation analysis vs 4.7% before mutation analysis, p = 0.0077). Very few pre-natal tests were requested. Of the 15 pre-natal tests, 12 had an increased risk, resulting in termination of pregnancy in all but one. Diagnostic testing identified 68.5% of individuals to be positive by mutation analysis, while 31.5% of those with HD-like symptoms were not found to have the HD mutation. The positive diagnostic tests included 24.5% of individuals with no known prior family history of HD.
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  • Badole, S., et al. (author)
  • High-resolution imaging with the International LOFAR Telescope : Observations of the gravitational lenses MG 0751+2716 and CLASS B1600+434
  • 2022
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
  • Journal article (peer-reviewed)abstract
    • We present Low-Frequency Array (LOFAR) telescope observations of the radio-loud gravitational lens systems MG 0751+2716 and CLASS B1600+434. These observations produce images at 300 milliarcseconds (mas) resolution at 150 MHz. In the case of MG 0751+2716, lens modelling is used to derive a size estimate of around 2 kpc for the low-frequency source, which is consistent with a previous 27.4 GHz study in the radio continuum with Karl G. Jansky Very Large Array. This consistency implies that the low-frequency radio source is cospatial with the core-jet structure that forms the radio structure at higher frequencies, and no significant lobe emission or further components associated with star formation are detected within the magnified region of the lens. CLASS B1600+434 is a two-image lens where one of the images passes through the edge-on spiral lensing galaxy, and the low radio frequency allows us to derive limits on propagation effects, namely scattering, in the lensing galaxy. The observed flux density ratio of the two lensed images is 1.19 ± 0.04 at an observed frequency of 150 MHz. The widths of the two images give an upper limit of 0.035 kpc m−20∕3 on the integrated scattering column through the galaxy at a distance approximately 1 kpc above its plane, under the assumption that image A is not affected by scattering. This is relatively small compared to limits derived through very long baseline interferometry studies of differential scattering in lens systems. These observations demonstrate that LOFAR is an excellent instrument for studying gravitational lenses. We also report on the inability to calibrate three further lens observations: two from early observations that have less well determined station calibration, and a third observation impacted by phase transfer problems.
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  • Garg, S, et al. (author)
  • Self-monitoring of blood glucose
  • 2010
  • In: International journal of clinical practice. Supplement. - : Hindawi Limited. - 1368-504X .- 1368-5031 .- 1742-1241. ; 64:166, s. 1-69
  • Journal article (peer-reviewed)
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  • Ilhan, Emre, et al. (author)
  • What is the definition of acute episodic and chronic pain in critically ill neonates and infants? A global, four-stage consensus and validation study
  • 2022
  • In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:3
  • Journal article (peer-reviewed)abstract
    • Objectives: To define and validate types of pain in critically ill neonates and infants by researchers and clinicians working in the neonatal intensive care unit (NICU) and high dependency unit (HDU).Design: A qualitative descriptive mixed-methods design.Procedure/s: Each stage of the study was built on and confirmed the previous stages. Stage 1 was an expert panel to develop definitions; stage 2 was a different expert panel made up of neonatal clinicians to propose clinical characteristics associated with the definitions from stage 1; stage 3 was a focus group of neonatal clinicians to provide clinical case scenarios associated with each definition and clinical characteristics; and stage 4 was a survey administered to neonatal clinicians internationally to test the validity of the definitions using the clinical case scenarios.Results: In stage 1, the panel (n=10) developed consensus definitions for acute episodic pain and chronic pain in neonates and infants. In stage 2, a panel (n=8) established clinical characteristics that may be associated with each definition. In stage 3, a focus group (n=11) created clinical case scenarios of neonates and infants with acute episodic pain, chronic pain and no pain using the definitions and clinical characteristics. In stage 4, the survey (n=182) revealed that the definitions allowed an excellent level of discrimination between case scenarios that described neonates and infants with acute episodic pain and chronic pain (area under the receiver operating characteristic=0.87 and 0.89, respectively).Conclusions: This four-stage study enabled the development of consensus-based and clinically valid definitions of acute episodic pain and chronic pain. There is a need to define and validate other pain types to inform a taxonomy of pain experienced by neonates and infants in the NICU and HDU.
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  • Maxwell, D J, et al. (author)
  • Serotoninergic and noradrenergic axonal contacts associated with premotor interneurons in spinal pathways from group II muscle afferents.
  • 2000
  • In: The European journal of neuroscience. - : Wiley. - 0953-816X. ; 12:4, s. 1271-80
  • Journal article (peer-reviewed)abstract
    • We investigated the possibility that monoaminergic axons make contacts with spinal interneurons which project to motor nuclei and are monosynaptically activated by group II muscle afferents. Interneurons in midlumbar spinal segments of adult cats were characterized electrophysiologically and intracellularly labelled with tetramethylrhodamine dextran. Serotoninergic and noradrenergic axons were identified with immunofluorescence in sections containing labelled cells. Contacts between monoaminergic axons and interneurons were investigated with three-colour confocal laser scanning microscopy and analysed with a computer reconstruction program. Cell bodies and dendritic trees of five cells were reconstructed and putative contacts were plotted. The average number of contacts formed by serotoninergic axons was 140 and the average number of noradrenergic contacts was 38. The majority (95%) of contacts were formed with dendrites; these were distributed over the entire dendritic tree, even on the most distal branches. These findings provide a morphological basis for the modulatory actions of monoamines on premotor spinal interneurons in pathways from group II muscle afferents.
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  • Maxwell, D J, et al. (author)
  • Synaptic connections of dorsal horn group II spinal interneurons: synapses formed with the interneurons and by their axon collaterals.
  • 1997
  • In: The Journal of comparative neurology. - 0021-9967. ; 380:1, s. 51-69
  • Journal article (peer-reviewed)abstract
    • Five dorsal horn interneurons with monosynaptic input from group II primary afferent fibres were physiologically characterized and intracellularly labelled with horseradish peroxidase. The cells were prepared for combined light and electron microscopy, and synaptic arrangements formed by axon collaterals of interneurons and synapses formed with their dendrites and somata were examined with the electron microscope. Immunogold reactions for gamma-aminobutyric acid, glycine and glutamate were performed to determine if these synapses were excitatory or inhibitory. Axon collaterals in lamina VI formed synapses with somata and dendrites of other neurons, and collaterals of one cell also formed axoaxonic synapses. It was concluded that one cell from the sample was inhibitory, whereas the remainder were probably excitatory. Dendrites and cell bodies of interneurons were contacted by several types of synaptic bouton. The first type of bouton displayed immunoreactivity for glutamate, the second type contained both gamma-aminobutyric acid and glycine, the third type contained glycine alone, and the fourth type contained gamma-aminobutyric acid alone. Some large glutamatergic boutons were postsynaptic to other boutons. Presynaptic boutons at these axoaxonic synapses always contained gamma-aminobutyric acid but a minority also contained glycine. The results of this study demonstrate the heterogeneity of dorsal horn group II interneurons and provide evidence that they include inhibitory and probably also excitatory neurons. Boutons originating from several chemically different classes of neuron are responsible for postsynaptic inhibition of these interneurons, and the presence of axoaxonic synapses indicates that their excitatory input is also controlled presynaptically.
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  • Riddell, J. S., et al. (author)
  • Organization of neuronal systems mediating presynaptic inhibition of group II muscle afferents in the cat.
  • 1995
  • In: The Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 483, s. 443-460
  • Journal article (peer-reviewed)abstract
    • 1. The organization of neuronal systems mediating presynaptic control of transmission from group II muscle afferent fibres has been investigated by comparing the sources of presynaptic inhibition of fibres terminating in different segments of the spinal cord: fibres of the semitendinosus and lateral gastrocnemius muscle nerves terminating in the sacral segments and of the tibialis anterior and extensor digitorum longus muscle nerves terminating in the midlumbar segments. 2. Two measures of presynaptic inhibition were used: depolarization of the terminals of group II fibres (detected as changes in the excitability of single fibres to electrical stimuli) and a decrease in the effectiveness of their synaptic actions (detected as a decrease in the amplitude of monosynaptic field potentials evoked by group II muscle afferents). 3. Group II muscle afferents strongly depolarized all of the group II afferent fibres, while group I muscle afferents contributed to the depolarization of only a few. The majority of fibres were as effectively depolarized by cutaneous afferents as by the most effective muscle afferents. However, the effectiveness with which afferents of different nerves depolarized group II muscle afferent fibres in the sacral and midlumbar segments differed. The most effective afferents were those of nerves that provide the main input to dorsal horn interneurones in the same region of the spinal cord. The sources of depolarization of flexor and extensor fibres terminating in the same (sacral) segments were very similar. 4. The amplitudes of field potentials evoked by group II afferents were depressed by the same types of afferent as produced depolarization of group II afferent fibres. There was also a strong correlation between the effectiveness with which afferents of a given nerve induced depolarization of single fibres and depression of field potentials in the same segments. Since group II field potentials were depressed to a greater extent (by up to 90%) than group I field potentials (by no more than 20%) concurrently recorded in the intermediate zone of midlumbar segments, it appears that transmission from group II muscle afferents may be more strongly affected by presynaptic inhibition than that from group I muscle afferents. 5. The results suggest that the interneuronal systems responsible for the presynaptic control of transmission from group II muscle afferents have topographically restricted actions and an organization appropriate to a system of negative feedback control. © 1995 The Physiological Society
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  • Sansoni, P, et al. (author)
  • New advances in CMV and immunosenescence
  • 2014
  • In: Experimental gerontology. - : Elsevier BV. - 1873-6815 .- 0531-5565. ; 55, s. 54-62
  • Journal article (other academic/artistic)
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  • Chapuis, AG, et al. (author)
  • HIV-specific CD8+ T cells from HIV+ individuals receiving HAART can be expanded ex vivo to augment systemic and mucosal immunity in vivo
  • 2011
  • In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 117:20, s. 5391-5402
  • Journal article (peer-reviewed)abstract
    • Most HIV+ individuals require lifelong highly active antiretroviral therapy (HAART) to suppress HIV replication, but fail to eliminate the virus in part because of residual replication in gut-associated lymphoid tissues (GALT). Naturally elicited HIV-specific CD8+ T cells generated in the acute and chronic infectious phases exhibit antiviral activity, but decrease in number after HAART. Therapeutic vaccines represent a potential strategy to expand cellular responses, although previous efforts have been largely unsuccessful, conceivably because of a lack of responding HIV-specific central-memory CD8+ T cells (Tcm). To determine whether patients receiving HAART possess CD8+ T cells with Tcm qualities that are amenable to augmentation, HIV-specific CD8+ T-cell clones were derived from HIV-reactive CD28+CD8+ T-cell lines isolated from 7 HIV+ HAART-treated patients, expanded ex vivo, and reinfused into their autologous host. Tracking of the cells in vivo revealed that clones could persist for ≥ 84 days, maintain expression and/or re-express CD28, up-regulate CD62L, secrete IL-2, proliferate on cognate Ag encounter and localize to the rectal mucosa. These results suggest some infused cells exhibited phenotypic and functional characteristics shared with Tcm in vivo, and imply that more effective therapeutic vaccination strategies targeting CD8+ Tcm in patients on HAART might provide hosts with expanded, long-lasting immune responses not only systemically but also in GALT. This study is registered at www.clinicaltrials.gov as NCT00110578.
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  • Cook, A, et al. (author)
  • Neonatal invasive candidiasis in low- and middle-income countries: Data from the NeoOBS study
  • 2023
  • In: Medical mycology. - : Oxford University Press (OUP). - 1460-2709 .- 1369-3786. ; 61:3
  • Journal article (peer-reviewed)abstract
    • Neonatal invasive candidiasis (NIC) has significant morbidity and mortality. Reports have shown a different profile of those neonates affected with NIC and of fluconazole-resistant Candida spp. isolates in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe the epidemiology, Candida spp. distribution, treatment, and outcomes of neonates with NIC from LMICs enrolled in a global, prospective, longitudinal, observational cohort study (NeoOBS) of hospitalized infants &lt;60 days postnatal age with sepsis (August 2018–February 2021). A total of 127 neonates from 14 hospitals in 8 countries with Candida spp. isolated from blood culture were included. Median gestational age of affected neonates was 30 weeks (IQR: 28–34), and median birth weight was 1270 gr (interquartile range [IQR]: 990–1692). Only a minority had high-risk criteria, such as being born &lt;28 weeks, 19% (24/127), or birth weight &lt;1000 gr, 27% (34/127). The most common Candida species were C. albicans (n = 45, 35%), C. parapsilosis (n = 38, 30%), and Candida auris (n = 18, 14%). The majority of C. albicans isolates were fluconazole susceptible, whereas 59% of C. parapsilosis isolates were fluconazole-resistant. Amphotericin B was the most common antifungal used [74% (78/105)], followed by fluconazole [22% (23/105)]. Death by day 28 post-enrollment was 22% (28/127). To our knowledge, this is the largest multi-country cohort of NIC in LMICs. Most of the neonates would not have been considered at high risk for NIC in HICs. A substantial proportion of isolates was resistant to first choice fluconazole. Understanding the burden of NIC in LMIC is essential to guide future research and treatment guidelines.
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