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1.
  • Bousquet, J., et al. (författare)
  • Building Bridges for Innovation in Ageing : Synergies between Action Groups of the EIP on AHA
  • 2017
  • Ingår i: The Journal of Nutrition, Health & Aging. - : Springer Nature. - 1279-7707 .- 1760-4788. ; 21:1, s. 92-104
  • Tidskriftsartikel (refereegranskat)abstract
    • The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).
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2.
  • de Heus, R. A. A., et al. (författare)
  • Blood Pressure Lowering With Nilvadipine in Patients With Mild-to-Moderate Alzheimer Disease Does Not Increase the Prevalence of Orthostatic Hypotension
  • 2019
  • Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 8:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-Hypertension is common among patients with Alzheimer disease. Because this group has been excluded from hypertension trials, evidence regarding safety of treatment is lacking. This secondary analysis of a randomized controlled trial assessed whether antihypertensive treatment increases the prevalence of orthostatic hypotension (OH) in patients with Alzheimer disease. Methods and Results-Four hundred seventy-seven patients with mild-to-moderate Alzheimer disease were randomized to the calcium-channel blocker nilvadipine 8 mg/day or placebo for 78 weeks. Presence of OH (blood pressure drop >= 20/>= 10 mm Hg after 1 minute of standing) and OH-related adverse events (dizziness, syncope, falls, and fractures) was determined at 7 follow-up visits. Mean age of the study population was 72.2 +/- 8.2 years and mean Mini-Mental State Examination score was 20.4 +/- 3.8. Baseline blood pressure was 137.8 +/- 14.0/77.0 +/- 8.6 mm Hg. Grade I hypertension was present in 53.4% (n=255). After 13 weeks, blood pressure had fallen by -7.8/-3.9 mm Hg for nilvadipine and by -0.4/-0.8 mm Hg for placebo (P<0.001). Across the 78-week intervention period, there was no difference between groups in the proportion of patients with OH at a study visit (odds ratio [95% CI] 1.1 [0.8-1.5], P 0.62), nor in the proportion of visits where a patient met criteria for OH, corrected for number of visits (7.7 +/- 13.8% versus 7.3 +/- 11.6%). OH-related adverse events were not more often reported in the intervention group compared with placebo. Results were similar for those with baseline hypertension. Conclusions-This study suggests that initiation of a low dose of antihypertensive treatment does not significantly increase the risk of OH in patients with mild-to-moderate Alzheimer disease.
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3.
  • Dyer, A. H., et al. (författare)
  • Cognitive Outcomes of Long-term Benzodiazepine and Related Drug (BDZR) Use in People Living With Mild to Moderate Alzheimer's Disease: Results From NILVAD
  • 2020
  • Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610. ; 21:2, s. 194-200
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Benzodiazepines and related drugs (BDZRs) have been associated with an increased risk of Alzheimer's disease (AD) in later life. Despite this, it remains unclear whether ongoing BDZR use may further accelerate cognitive decline in those diagnosed with mild to moderate AD. Design: This study was embedded within NILVAD, a randomized controlled trial of nilvadipine in mild to moderate AD. Cognition was measured at baseline and 18 months using the Alzheimer Disease Assessment Scale, Cognitive Subsection (ADAS-Cog). We assessed predictors of long-term BDZR use and analyzed the effect of ongoing BDZR use on ADAS-Cog scores at 18 months. Additionally, the impact of BDZR use on adverse events, incident delirium, and falls over 18-month follow-up was assessed adjusting for relevant covariates. Setting and Participants: 448 participants with mild to moderate AD recruited from 23 academic centers in 9 European countries. Results: Overall, 14% (62/448) were prescribed an ongoing BDZR for the study duration. Increasing total number of (non-BDZR) medications was associated with a greater likelihood of BDZR prescription (odds ratio 1.16, 95% confidence interval 1.05-1.29). At 18 months, BDZR use was not associated with greater cognitive decline on the ADAS-Cog controlling for baseline ADAS-Cog scores, age, gender, study arm, and other clinical covariates (beta = 1.62, -1.34 to 4.56). However, ongoing BDZR use was associated with a greater likelihood of adverse events [incidence rate ratio (IRR) 1.19, 1.05-1.34], incident delirium (IRR 2.31, 1.45-3.68), and falls (IRR 1.66, 1.02-2.65) over 18 months that persisted after robust adjustment for covariates. Conclusions and Implications: This study found no effect of ongoing BDZR use on ADAS-Cog scores in those with mild to moderate AD over 18 months. However, ongoing use of these medications was associated with an increased risk of adverse events, delirium, and falls. Thus, BDZR use should be avoided where possible and deprescribing interventions should be encouraged in older adults with AD. (C) 2019 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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5.
  • Lyons, PA, et al. (författare)
  • Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 5120-
  • Tidskriftsartikel (refereegranskat)abstract
    • Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.
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6.
  • Williams, Angus A., et al. (författare)
  • THE Gaia-ESO Survey : Metal-rich bananas in the bulge
  • 2016
  • Ingår i: Astrophysical Journal Letters. - 2041-8205. ; 824:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We analyze the kinematics of ∼2000 giant stars in the direction of the Galactic bulge, extracted from the Gaia-ESO survey in the region -10° ≲ l≲ 10° and -11° ≲ b ≲ -3°. We find distinct kinematic trends in the metal-rich ([M H] > 0) and metal-poor ([M H] <0) stars in the data. The velocity dispersion of the metal-rich stars drops steeply with latitude, compared to a flat profile in the metal-poor stars, as has been seen previously. We argue that the metal-rich stars in this region are mostly on orbits that support the boxy-peanut shape of the bulge, which naturally explains the drop in their velocity dispersion profile with latitude. The metal-rich stars also exhibit peaky features in their line of sight velocity histograms, particularly along the minor axis of the bulge. We propose that these features are due to stars on resonant orbits supporting the boxy-peanut bulge. This conjecture is strengthened through the comparison of the minor axis data with the velocity histograms of resonant orbits generated in simulations of buckled bars. The "banana" or 2:1:2 orbits provide strongly bimodal histograms with narrow velocity peaks that resemble the Gaia-ESO metal-rich data.
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7.
  • Brisby, Helena, 1965, et al. (författare)
  • The effect of running exercise on intervertebral disc extracellular matrix production in a rat model
  • 2010
  • Ingår i: Spine. - 1528-1159. ; 35:15, s. 1429-1436
  • Tidskriftsartikel (refereegranskat)abstract
    • STUDY DESIGN: Using a running rat model, the effects of physical exercise on cellular function and intervertebral disc (IVD) extracellular matrix were studied. OBJECTIVE: To investigate whether 3-weeks treadmill running exercise can stimulate matrix production and cellular proliferation of the IVD. SUMMARY OF BACKGROUND DATA: Appropriate physical exercise plays an important role in the treatment of patients with low back pain-associated IVD disorder. However, it is unknown how regular exercise affects the disc at the cellular level. METHODS: Twelve Sprague-Dawley rats underwent a daily treadmill exercise regime for a total of 3 weeks. Twelve nonexercised rats served as controls. The spinal lumbar IVD were collected and paraffin embedded for histologic analysis. Cell counts were determined on hematoxylin-eosin- and Masson-Trichrome-stained paraffin sections. Protein expression of collagen-I, collagen-II, aggrecan, Sox-9, and Sox-6 was evaluated with immunohistochemical staining. mRNA expression of Sox-9 and collagen-2 were studied by in situ hybridization. Proteoglycans were visualized with Alcian blue. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. RESULTS: The cell numbers in the anulus fibrosus (AF) increased by 25% (P < 0.05) after 3 weeks of exercise. Collagen-2 and Sox-9 mRNA were strongly expressed in the nucleus pulposus (NP) samples of the running group, but weakly expressed in the controls. An increase in collagen-II, aggrecan, and Sox-9 protein expression in NP and AF regions of the disc was detected in the exercised rats compared with controls. Quantification of Alcian blue staining demonstrated increased proteoglycan in both NP (8-fold) and AF (7-fold) in the exercised group compared with controls (P < 0.05). In addition, no significant differences were observed between the experimental groups in cellular apoptosis, collagen-I, or Sox-6 expression. CONCLUSION: In this study, increased extracellular matrix production and cell proliferation with no induction of disc cell apoptosis was observed in the lumbar IVD after a 3-week running regimen in rats, suggesting that regular exercise may have an augmentative effect on cells and matrix production.
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8.
  • Michels, F., et al. (författare)
  • Searching for consensus in the approach to patients with chronic lateral ankle instability: ask the expert
  • 2018
  • Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 26:7, s. 2095-2102
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study is to propose recommendations for the treatment of patients with chronic lateral ankle instability (CAI) based on expert opinions. A questionnaire was sent to 32 orthopaedic surgeons with clinical and scientific experience in the treatment of CAI. The questions were related to preoperative imaging, indications and timing of surgery, technical choices, and the influence of patient-related aspects. Thirty of the 32 invited surgeons (94%) responded. Consensus was found on several aspects of treatment. Preoperative MRI was routinely recommended. Surgery was considered in patients with functional ankle instability after 3-6 months of non-surgical treatment. Ligament repair is still the treatment of choice in patients with mechanical instability; however, in patients with generalized laxity or poor ligament quality, lateral ligament reconstruction (with grafting) of both the ATFL and CFL should be considered. Most surgeons request an MRI during the preoperative planning. There is a trend towards earlier surgical treatment (after failure of non-surgical treatment) in patients with mechanical ligament laxity (compared with functional instability) and in high-level athletes. This study proposes an assessment and a treatment algorithm that may be used as a recommendation in the treatment of patients with CAI.
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9.
  • Moore, Keith J M, et al. (författare)
  • Loop-Mediated Isothermal Amplification Detection of SARS-CoV-2 and Myriad Other Applications
  • 2021
  • Ingår i: Journal of Biomolecular Techniques. - : Association of Biomolecular Resource Facilities. - 1524-0215 .- 1943-4731. ; 32:3, s. 228-275
  • Forskningsöversikt (refereegranskat)abstract
    • As the second year of the COVID-19 pandemic begins, it remains clear that a massive increase in the ability to test for SARS-CoV-2 infections in a myriad of settings is critical to controlling the pandemic and to preparing for future outbreaks. The current gold standard for molecular diagnostics is the polymerase chain reaction (PCR), but the extraordinary and unmet demand for testing in a variety of environments means that both complementary and supplementary testing solutions are still needed. This review highlights the role that loop-mediated isothermal amplification (LAMP) has had in filling this global testing need, providing a faster and easier means of testing, and what it can do for future applications, pathogens, and the preparation for future outbreaks. This review describes the current state of the art for research of LAMP-based SARS-CoV-2 testing, as well as its implications for other pathogens and testing. The authors represent the global LAMP (gLAMP) Consortium, an international research collective, which has regularly met to share their experiences on LAMP deployment and best practices; sections are devoted to all aspects of LAMP testing, including preanalytic sample processing, target amplification, and amplicon detection, then the hardware and software required for deployment are discussed, and finally, a summary of the current regulatory landscape is provided. Included as well are a series of first-person accounts of LAMP method development and deployment. The final discussion section provides the reader with a distillation of the most validated testing methods and their paths to implementation. This review also aims to provide practical information and insight for a range of audiences: for a research audience, to help accelerate research through sharing of best practices; for an implementation audience, to help get testing up and running quickly; and for a public health, clinical, and policy audience, to help convey the breadth of the effect that LAMP methods have to offer.
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11.
  • Messerli-Burgy, N, et al. (författare)
  • Psychological coping and recurrent major adverse cardiac events following acute coronary syndrome
  • 2015
  • Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 207:3, s. 256-261
  • Tidskriftsartikel (refereegranskat)abstract
    • Depressed mood and stress are associated with recurrent adverse outcomes following acute coronary syndrome (ACS), but the impact of psychological coping style has not been evaluated in detail.AimsWe tested the relationship between task-oriented coping and event-free survival following ACS.MethodWe followed 158 patients with ACS for an average of 59.8 months for major adverse cardiac outcomes. Psychological coping was assessed with the Coping Inventory of Stressful Situations.ResultsCompared with patients in the lower half of the distribution, those reporting higher task-oriented coping had a reduced hazard of adverse cardiac events (hazard ratio (HR) = 0.28, 95% CI 0.11–0.68, P=0.005) independently of demographic, clinical and behavioural covariates. The combination of low task-oriented coping and high depressive symptoms showed a strong association with adverse outcomes (HR = 6.25, 95% CI 1.88–20.82, P=0.003).ConclusionsThe tendency to cope using task-oriented strategies may promote event-free survival following ACS.
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12.
  • Meulenbroek, O., et al. (författare)
  • European multicentre double-blind placebo-controlled trial of Nilvadipine in mild-to-moderate Alzheimer's disease - The substudy protocols: NILVAD frailty; NILVAD blood and genetic biomarkers; NILVAD cerebrospinal fluid biomarkers; NILVAD cerebral blood flow
  • 2016
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 6:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: In conjunction with the NILVAD trial, a European Multicentre Double-Blind Placebo Controlled trial of Nilvadipine in Mild-to-Moderate Alzheimer's disease (AD), there are four NILVAD substudies in which eligible NILVAD patients are also invited to participate. The main NILVAD protocol was previously published in BMJ Open (2014). The objectives of the NILVAD substudies are to determine whether frailty, cerebrospinal fluid (CSF), blood biomarker profile and Apolipoprotein E (APOE) status predict response to Nilvadipine, and to investigate the effect of Nilvadipine on cerebral blood flow and blood biomarkers. Methods and analysis: All participants who fulfil criteria for the main NILVAD study are eligible for participation in the NILVAD substudies. Participation is subject to informed consent and whether the substudy is available at a particular NILVAD study site. Each substudy entails extra measurements during the course of the main NILVAD study. For example, in the blood and genetic biomarkers substudy, extra blood (30 mL) will be collected at week 0, week 13, week 52 and week 78, while in the cerebral blood flow substudy, participants will receive an MRI and transcranial Doppler measurements at week 0, week 26 and week 78. In the CSF substudy, 10 mL CSF is collected at week 0 and week 78. Ethics and dissemination: All NILVAD substudies and all subsequent amendments have received ethical approval within each participating country, according to national regulations. Each participant provides written consent to participate. All participants remain anonymised throughout and the results of each substudy will be published in an international peer reviewed journal. © 2016 Published by the BMJ Publishing Group Limited.
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13.
  • Shea, T. J., et al. (författare)
  • Overview and status of diagnostics for the ESS project
  • 2018
  • Ingår i: Proceedings of the 6th International Beam Instrumentation Conference, IBIC 2017. - 9783954501922 ; , s. 8-15
  • Konferensbidrag (refereegranskat)abstract
    • The European Spallation Source, now under construction in Lund, Sweden, aims to be the world's most powerful pulsed neutron scattering facility. Driving the neutron source is a 5 MW superconducting proton linear accelerator operating at 4 percent beam duty factor and 14 Hz repetition rate. Nineteen partner institutions from across Europe are working with the Accelerator Division in Lund to design and construct the accelerator. The suite of accelerator instrumentation consists of over 20 unique system types developed by over 20 partners and collaborators. Although the organizational complexity presents challenges, it also provides the vast capabilities required to achieve the technical goals. At this time, the beam instrumentation team is in transition, completing the design phase while scaling up to the deployment phase. Commissioning of the ion source has commenced in Catania, preparations for installation on the Lund site are ramping up, and basic R&D on target instrumentation continues. Beam commissioning results from the systems immediately following the ion source will be presented, along with technical highlights and status of the many remaining instrumentation systems.
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14.
  • Shelton, Jennifer M. G., et al. (författare)
  • Genetic determinants of anti-malarial acquired immunity in a large multi-centre study
  • 2015
  • Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels. Methods: Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP) 4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels. Results: Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)(4) epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2. Conclusion: Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of combining data from sites with heterogeneous malaria transmission levels across Africa and Asia with which to explore genetic effects on anti-malarial immunity.
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15.
  • Sjöberg, Karin, et al. (författare)
  • Multi-decadal surface ozone trends at globally distributed remote locations.
  • 2020
  • Ingår i: Elementa. - : University of California Press. - 2325-1026. ; 8:23
  • Tidskriftsartikel (refereegranskat)abstract
    • Extracting globally representative trend information from lower tropospheric ozone observations is extremely difficult due to the highly variable distribution and interannual variability of ozone, and the ongoing shift of ozone precursor emissions from high latitudes to low latitudes. Here we report surface ozone trends at 27 globally distributed remote locations (20 in the Northern Hemisphere, 7 in the Southern Hemisphere), focusing on continuous time series that extend from the present back to at least 1995. While these sites are only representative of less than 25% of the global surface area, this analysis provides a range of regional long-term ozone trends for the evaluation of global chemistry-climate models. Trends are based on monthly mean ozone anomalies, and all sites have at least 20 years of data, which improves the likelihood that a robust trend value is due to changes in ozone precursor emissions and/or forced climate change rather than naturally occurring climate variability. Since 1995, the Northern Hemisphere sites are nearly evenly split between positive and negative ozone trends, while 5 of 7 Southern Hemisphere sites have positive trends. Positive trends are in the range of 0.5–2 ppbv decade–1, with ozone increasing at Mauna Loa by roughly 50% since the late 1950s. Two high elevation Alpine sites, discussed by previous assessments, exhibit decreasing ozone trends in contrast to the positive trend observed by IAGOS commercial aircraft in the European lower free-troposphere. The Alpine sites frequently sample polluted European boundary layer air, especially in summer, and can only be representative of lower free tropospheric ozone if the data are carefully filtered to avoid boundary layer air. The highly variable ozone trends at these 27 surface sites are not necessarily indicative of free tropospheric trends, which have been overwhelmingly positive since the mid-1990s, as shown by recent studies of ozonesonde and aircraft observations.
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17.
  • Chatterjee, S., et al. (författare)
  • Protein Paucimannosylation Is an Enriched N-Glycosylation Signature of Human Cancers
  • 2019
  • Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 19:21-22
  • Tidskriftsartikel (refereegranskat)abstract
    • While aberrant protein glycosylation is a recognized characteristic of human cancers, advances in glycoanalytics continue to discover new associations between glycoproteins and tumorigenesis. This glycomics‐centric study investigates a possible link between protein paucimannosylation, an under‐studied class of human N‐glycosylation [Man1‐3GlcNAc2Fuc0‐1], and cancer. The paucimannosidic glycans (PMGs) of 34 cancer cell lines and 133 tissue samples spanning 11 cancer types and matching non‐cancerous specimens are profiled from 467 published and unpublished PGC‐LC‐MS/MS N‐glycome datasets collected over a decade. PMGs, particularly Man2‐3GlcNAc2Fuc1, are prominent features of 29 cancer cell lines, but the PMG level varies dramatically across and within the cancer types (1.0–50.2%). Analyses of paired (tumor/non‐tumor) and stage‐stratified tissues demonstrate that PMGs are significantly enriched in tumor tissues from several cancer types including liver cancer (p = 0.0033) and colorectal cancer (p = 0.0017) and is elevated as a result of prostate cancer and chronic lymphocytic leukaemia progression (p < 0.05). Surface expression of paucimannosidic epitopes is demonstrated on human glioblastoma cells using immunofluorescence while biosynthetic involvement of N‐acetyl‐β‐hexosaminidase is indicated by quantitative proteomics. This intriguing association between protein paucimannosylation and human cancers warrants further exploration to detail the biosynthesis, cellular location(s), protein carriers, and functions of paucimannosylation in tumorigenesis and metastasis.
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19.
  • Farricker, A., et al. (författare)
  • Beam Dynamics in the ESS Linac under the Influence of Monopole and Dipole HOMs
  • 2015
  • Ingår i: Physics Procedia. - : Elsevier BV. - 1875-3892. ; 79, s. 21-29
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Spallation Source (ESS), planned to be operational in 2019, is anticipated to be the worlds most intense neutron source. The total beam power will be 5 MW. We focus on the impact of manufacturing errors on the beam quality. In particular we assess the emittance dilution which occurs due to Higher Order Modes (HOMs) excited at a harmonic of the bunch frequency. We also discuss some alignment issues pertaining to the cavities.
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20.
  • Fu, Jinglin, et al. (författare)
  • Survey of bidirectional transmittance distribution function measurement facilities by multilateral scale comparisons
  • 2024
  • Ingår i: Metrologia. - : Institute of Physics. - 0026-1394 .- 1681-7575. ; 61:3
  • Tidskriftsartikel (refereegranskat)abstract
    • In recent years, a growing demand for the capability of performing accurate measurements of the bidirectional transmittance distribution function (BTDF) has been observed in industry, research and development, and aerospace applications. However, there exists no calibration and measurement capabilities-entry for BTDF in the database of the Bureau International des Poids et Mesures and to date no BTDF comparison has been conducted between different national metrology institutes (NMIs) or designated institutes (DIs). As a first step to a possible future key comparison and to test the existing capabilities of determining this measurand, two interlaboratory comparisons were performed. In comparison one, five samples of three different types of optical transmissive diffusers were measured by five NMIs and one DI. By specific sample choice, the focus for this study lay more on orientation-dependent scatter properties. In comparison two, where one NMI, one DI, one university, and three industrial partners investigated their measurement capabilities, the dependence on the orientation was not assessed, but two additional samples of the same material and different thickness were measured. Results of the two comparisons are presented, giving a good overview of existing experimental solutions, and showing specific sample-related problems to be solved for improved future BTDF measurements.
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22.
  • Lawlor, B., et al. (författare)
  • NILVAD protocol: A European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease
  • 2014
  • Ingår i: BMJ Open. - : BMJ Publishing Group. - 2044-6055. ; 4:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82 weeks with a treatment period of 78 weeks. Methods and analysis: Adult patients, males and females over 50 years with mild-to-moderate AD as defined by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease and Related Disorders Association (NINCDSADRDA) criteria, will be included in the study. It aims to recruit a total of 500 patients with AD; 250 in the nilvadipine group and 250 in the placebo group. Participants will be randomised to receive nilvadipine, an 8 mg overencapsulated, sustained release capsule, or a matching overencapsulated placebo (sugar pill) for a period of 78 weeks of treatment. The primary efficacy outcome measure in this study is the change in cognitive function as assessed by the Alzheimer's disease Assessment Scale (ADASCog 12) from baseline to the end of treatment duration (78 weeks). There are two key secondary outcome measures, the Clinical Dementia Rating Scale Sum of Boxes (CDRsb) and the Disability Assessment for Dementia (DAD). If a statistically significant effect is seen in the primary outcome, CDRsb will be considered to be a coprimary end point and only the DAD will contribute to the secondary outcome analysis. Ethics and dissemination: The study and all subsequent amendments have received ethical approval within each participating country according to national regulations. Each participant will provide written consent to participate in the study. All participants will remain anonymised throughout and the results of the study will be published in an international peerreviewed journal. Trial registration number EUDRACT Reference Number: 201200276427.
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23.
  • Messerli-Bürgy, N, et al. (författare)
  • Cortisol levels and history of depression in acute coronary syndrome patients.
  • 2012
  • Ingår i: Psychological Medicine. - 0033-2917 .- 1469-8978. ; 42:9, s. 1815-1823
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Depressed mood following an acute coronary syndrome (ACS) is a risk factor for future cardiac morbidity. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation is associated with depression, and may be a process through which depressive symptoms influence later cardiac health. Additionally, a history of depression predicts depressive symptoms in the weeks following ACS. The purpose of this study was to determine whether a history of depression and/or current depression are associated with the HPA axis dysregulation following ACS.METHOD: A total of 152 cardiac patients completed a structured diagnostic interview, a standardized depression questionnaire and a cortisol profile over the day, 3 weeks after an ACS. Cortisol was analysed using: the cortisol awakening response (CAR), total cortisol output estimated using the area under the curve method, and the slope of cortisol decline over the day.RESULTS: Total cortisol output was positively associated with history of depression, after adjustment for age, gender, marital status, ethnicity, smoking status, body mass index (BMI), Global Registry of Acute Cardiac Events (GRACE) risk score, days in hospital, medication with statins and antiplatelet compounds, and current depression score. Men with clinically diagnosed depression after ACS showed a blunted CAR, but the CAR was not related to a history of depression.CONCLUSIONS: Patients with a history of depression showed increased total cortisol output, but this is unlikely to be responsible for associations between depression after ACS and later cardiac morbidity. However, the blunted CAR in patients with severe depression following ACS indicates that HPA dysregulation is present.
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24.
  • Molloy, EJ, et al. (författare)
  • Neonates in the COVID-19 pandemic
  • 2021
  • Ingår i: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 89:65, s. 1038-1040
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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25.
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26.
  • Molloy, E, et al. (författare)
  • Use of bidirectional transmittance distribution function measurements to determine transmittance haze
  • 2023
  • Ingår i: Metrologia. - : Institute of Physics. - 0026-1394 .- 1681-7575. ; 60:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Accurate and traceable measurements of transmittance haze are required for quality control in various different industries, such as optoelectronics, automobiles, and agriculture. Transmittance haze is defined as the fraction of light transmitted through a material that deviates from the incident beam by more than 2.5∘. Various documentary standards specify the use of an integrating sphere with a prescribed geometry for the measurement of transmittance haze. This paper uses goniometric measurements of the bidirectional transmittance distribution function (BTDF) to calculate transmittance haze according to the definition and demonstrates that the sphere-based realisation of transmittance haze specified in the documentary standards does not agree with the definition, with the difference being up to 20% for some samples. The BTDF measurements are also used to simulate the integrating sphere haze, allowing the sensitivity of the sphere haze to errors in the integrating sphere geometry to be calculated. 
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27.
  • Molloy, Gunilla, et al. (författare)
  • Pojkars läsning
  • 2007
  • Ingår i: Svenskläraren. ; 51:2, s. 9-23
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
28.
  • Münch, Andreas, 1970-, et al. (författare)
  • Undiagnosed microscopic colitis : a hidden cause of chronic diarrhoea and a frequently missed treatment opportunity
  • 2020
  • Ingår i: FRONTLINE GASTROENTEROLOGY. - : BMJ Publishing Group Ltd. - 2041-4137 .- 2041-4145. ; 11:3, s. 228-234
  • Forskningsöversikt (refereegranskat)abstract
    • Microscopic colitis (MC) is a treatable cause of chronic, non-bloody, watery diarrhoea, but physicians (particularly in primary care) are less familiar with MC than with other causes of chronic diarrhoea. The colon in patients with MC is usually macroscopically normal. MC can only be diagnosed by histological examination of colonic biopsies (subepithelial collagen band >10 mu m (collagenous colitis) or >20 intraepithelial lymphocytes per 100 epithelial cells (lymphocytic colitis), both with lamina propria inflammation). The UK National Health Service exerts downward pressure to minimise colonoscopy referrals. Furthermore, biopsies are often not taken according to guidelines. These factors work against MC diagnosis. In this review, we note the high incidence of MC (comparable to ulcerative colitis and Crohns disease) and its symptomatic overlap with irritable bowel syndrome. We also highlight problems with the recommendation by National Health Service/National Institute for Health and Care Excellence guidelines for inflammatory bowel diseases that colonoscopy referrals should be based on a faecal calprotectin level of >= 100 mu g/g. Faecal calprotectin is <100 mu g/g in over half of individuals with active MC, building into the system a propensity to misdiagnose MC as irritable bowel syndrome. This raises important questions-how many patients with MC have already been misdiagnosed, and how do we address this silent burden? Clarity is needed around pathways for MC management; MC is poorly acknowledged by the UK healthcare system and it is unlikely that best practices are being followed adequately. There is an opportunity to identify and treat patients with MC more effectively.
  •  
29.
  • Possolo, Antonio, et al. (författare)
  • Value assignment and uncertainty evaluation for single-element reference solutions
  • 2018
  • Ingår i: Metrologia. - : Institute of Physics Publishing (IOPP). - 0026-1394 .- 1681-7575. ; 55:3, s. 404-413
  • Tidskriftsartikel (refereegranskat)abstract
    • A Bayesian statistical procedure is proposed for value assignment and uncertainty evaluation for the mass fraction of the elemental analytes in single-element solutions distributed as NIST standard reference materials. The principal novelty that we describe is the use of information about relative differences observed historically between the measured values obtained via gravimetry and via high-performance inductively coupled plasma optical emission spectrometry, to quantify the uncertainty component attributable to between-method differences. This information is encapsulated in a prior probability distribution for the between-method uncertainty component, and it is then used, together with the information provided by current measurement data, to produce a probability distribution for the value of the measurand from which an estimate and evaluation of uncertainty are extracted using established statistical procedures.
  •  
30.
  • Smith, Siobhan, et al. (författare)
  • IL-16/miR-125a axis controls neutrophil recruitment in pristane-induced lung inflammation
  • 2018
  • Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 3:15
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe lung inflammation and alveolar hemorrhage can be life-threatening in systemic lupus erythematosus (SLE) patients if not treated early and aggressively. Neutrophil influx is the driver key of this pathology, but little is known regarding the molecular events regulating this recruitment. Here, we uncover a role for IL-16/mir-125a in this pathology and show not only that IL-16 is a target for miR-125a but that reduced miR-125a expression in SLE patients associates with lung involvement. Furthermore, in the pristane model of acute "SLE-like" lung inflammation and alveolar hemorrhage, we observed reduced pulmonary miR-125a and enhanced IL-16 expression. Neutrophil infiltration was markedly reduced in the peritoneal lavage of pristane-treated IL-16-deficient mice and elevated following i.n. delivery of IL-16. Moreover, a miR-125a mimic reduced pristane-induced IL-16 expression and neutrophil recruitment and rescued lung pathology. Mechanistically, IL-16 acts directly on the pulmonary epithelium and markedly enhances neutrophil chemoattractant expression both in vitro and in vivo, while the miR-125a mimic can prevent this. Our results reveal a role for miR-125a/IL-16 in regulating lung inflammation and suggest this axis may be a therapeutic target for management of acute lung injury in SLE.
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31.
  • Steptoe, A, et al. (författare)
  • Emotional triggering and low socio-economic status as determinants of depression following acute coronary syndrome.
  • 2011
  • Ingår i: Psychological Medicine. - 0033-2917 .- 1469-8978. ; 41:9, s. 1857-66
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The determinants of depression following acute coronary syndrome (ACS) are poorly understood. Triggering of ACS by emotional stress and low socio-economic status (SES) are predictors of adverse outcomes. We therefore investigated whether emotional triggering and low SES predict depression and anxiety following ACS.METHOD: This prospective observational clinical cohort study involved 298 patients with clinically verified ACS. Emotional stress was assessed for the 2 h before symptom onset and compared with the equivalent period 24 h earlier using case-crossover methods. SES was defined by household income and education. Depression was measured with the Beck Depression Inventory and the Hamilton Rating Scale for Depression and anxiety with the Hospital Anxiety and Depression Scale 3 weeks after ACS and again at 6 and 12 months. Age, gender, ethnicity, marital status, the Global Registry of Acute Coronary Events risk score, duration of hospital stay and history of depression were included as covariates.RESULTS: Emotional stress during the 2-h hazard period was associated with increased risk of ACS (odds ratio 1.88, 95% confidence interval 1.01-3.61). Both low income and emotional triggering predicted depression and anxiety at 3 weeks and 6/12 months independently of covariates. The two factors interacted, with the greatest depression and anxiety in lower income patients who experienced acute emotional stress. Education was not related to depression.CONCLUSIONS: Patients who experience acute emotional stress during their ACS and are lower SES as defined by current affluence and access to resources are particularly vulnerable to subsequent depression and anxiety.
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