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Sökning: WFRF:(Reid Malcolm)

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1.
  • Khatri, C, et al. (författare)
  • Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
  • 2021
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
  • 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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2.
  • Bravo, L, et al. (författare)
  • 2021
  • swepub:Mat__t
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3.
  • Tabiri, S, et al. (författare)
  • 2021
  • swepub:Mat__t
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4.
  • Chen, Zhishan, et al. (författare)
  • Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
  • 2024
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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5.
  • Dennis, Martin, et al. (författare)
  • Effects of fluoxetine on functional outcomes after acute stroke (FOCUS) : a pragmatic, double-blind, randomised, controlled trial
  • 2019
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 393:10168, s. 265-274
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762.Findings Between Sept 10,2012, and March 31,2017,3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99.3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0.951 [95% CI 0.839-1.079]; p=0.439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13.43%] patients vs 269 [17.21%]; difference 3.78% [95% CI 1.26-6.30]; p=0.0033), but they had more bone fractures (45 [2.88%] vs 23 [1.47%]; difference 1.41% [95% CI 0.38-2.43]; p=0.0070). There were no significant differences in any other event at 6 or 12 months.Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.
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6.
  • Fernandez-Rozadilla, Ceres, et al. (författare)
  • Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
  • 2023
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 55, s. 89-99
  • Tidskriftsartikel (refereegranskat)abstract
    • Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
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7.
  • Hammarberg, Anders, et al. (författare)
  • The effect of acamprosate on alcohol craving and correlation with hypothalamic pituitary adrenal (HPA) axis hormones and beta-endorphin
  • 2009
  • Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1305:Suppl., s. S2-S6
  • Tidskriftsartikel (refereegranskat)abstract
    • Acamprosate is a widely utilized, efficacious treatment for relapse prevention in alcohol dependent patients. The mechanism of acamprosate action is hypothesized to be by modulation of craving responses. Previous research has suggested that acamprosate may affect the hypothalamic pituitary adrenal (HPA) axis as well as beta-endorphin. The aim of the present study was to investigate if acamprosate attenuates alcohol craving following a short-term treatment, and if craving and drinking measures are correlated to changes in HPA-axis hormones and beta-endorphin. In a double-blind design, 56 alcohol dependent treatment seeking patients were randomized to 21 days of either acamprosate (1998 mg/day) or placebo treatment. Subjective, physiological and biological measurements were recorded at inclusion and on day 21. The results showed that acamprosate treated patients showed significantly reduced craving compared to placebo. Further, a significant correlation was shown between craving and alcohol consumption during study. No changes in hormonal levels were found in acamprosate treated patients compared to placebo.
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8.
  • Kunder, Andrea, et al. (författare)
  • THE RADIAL VELOCITY EXPERIMENT (RAVE) : FIFTH DATA RELEASE
  • 2017
  • Ingår i: The Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 153:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Data Release 5 (DR5) of the Radial Velocity Experiment (RAVE) is the fifth data release from a magnitude-limited (9 < I < 12) survey of stars randomly selected in the Southern Hemisphere. The RAVE medium-resolution spectra (R ∼ 7500) covering the Ca-triplet region (8410-8795 A) span the complete time frame from the start of RAVE observations in 2003 to their completion in 2013. Radial velocities from 520,781 spectra of 457,588 unique stars are presented, of which 255,922 stellar observations have parallaxes and proper motions from the Tycho-Gaia astrometric solution in Gaia DR1. For our main DR5 catalog, stellar parameters (effective temperature, surface gravity, and overall metallicity) are computed using the RAVE DR4 stellar pipeline, but calibrated using recent K2 Campaign 1 seismic gravities and Gaia benchmark stars, as well as results obtained from high-resolution studies. Also included are temperatures from the Infrared Flux Method, and we provide a catalog of red giant stars in the dereddened color - (J Ks) 0 interval (0.50, 0.85) for which the gravities were calibrated based only on seismology. Further data products for subsamples of the RAVE stars include individual abundances for Mg, Al, Si, Ca, Ti, Fe, and Ni, and distances found using isochrones. Each RAVE spectrum is complemented by an error spectrum, which has been used to determine uncertainties on the parameters. The data can be accessed via the RAVE Web site or the VizieR database.
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9.
  • Ort, Christoph, et al. (författare)
  • Spatial differences and temporal changes in illicit drug use in Europe quantified by wastewater analysis
  • 2014
  • Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 109:8, s. 1338-1352
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims To perform wastewater analyses to assess spatial differences and temporal changes of illicit drug use in a large European population. Design Analyses of raw wastewater over a 1-week period in 2012 and 2013. Setting and Participants Catchment areas of wastewater treatment plants (WWTPs) across Europe, as follows: 2012: 25 WWTPs in 11 countries (23 cities, total population 11.50 million); 2013: 47 WWTPs in 21 countries (42 cities, total population 24.74 million). Measurements Excretion products of five illicit drugs (cocaine, amphetamine, ecstasy, methamphetamine, cannabis) were quantified in wastewater samples using methods based on liquid chromatography coupled to mass spectrometry. Findings Spatial differences were assessed and confirmed to vary greatly across European metropolitan areas. In general, results were in agreement with traditional surveillance data, where available. While temporal changes were substantial in individual cities and years (P ranging from insignificant to <10(-3)), overall means were relatively stable. The overall mean of methamphetamine was an exception (apparent decline in 2012), as it was influenced mainly by four cities. Conclusions Wastewater analysis performed across Europe provides complementary evidence on illicit drug consumption and generally concurs with traditional surveillance data. Wastewater analysis can measure total illicit drug use more quickly and regularly than is the current norm for national surveys, and creates estimates where such data does not exist.
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10.
  • Reid, Malcolm, et al. (författare)
  • From the heat of the fire : a biography of an early bronze age battle-axe from church Lawton, Cheshire
  • 2024
  • Ingår i: The Antiquaries Journal. - 0003-5815 .- 1758-5309.
  • Tidskriftsartikel (refereegranskat)abstract
    • A battle-axe made of picrite from the Cwm Mawr rock source, near Hyssington, Powys, UK, was discovered during the archaeological excavation of two Early Bronze Age barrows at Church Lawton, near Alsager in Cheshire, UK, in 1982–3. It had been subjected to intense heat and then placed in a pit, next to the cremated remains of an adult, possibly a female. The heating has radically altered the appearance of the axe. Originally very smooth and dark grey-green, it now has a more granular and dusty feel, together with a mottled orange-reddish appearance. The Church Lawton battle-axe is particularly notable as it is among a small number of such artefacts in Britain to have been recovered from a barrow excavation conducted according to modern standards, as well as being directly associated with an interment dated by radiocarbon: 1893–1740 cal BC (3490 ± 29 BP). It is also the first implement from the Cwm Mawr rock source to be dated in this way. An initial examination of the battle-axe was conducted in the 1980s. A more exacting analysis of the object has now been undertaken, focusing on its petrology in relation to the rock source, its manufacture and use, and its heating. The new examination included the use of stereoscopic and metallographic microscopes. This paper details the new work and provides an enhanced understanding of the implement’s history and significance, emphasising the likely connections between the Early Bronze Age community at Church Lawton and others in the wider region.
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11.
  • Schlabach, Martin, et al. (författare)
  • Suspect screening in Nordic countries : point sources in city areas
  • 2017
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • This report describes the results of a suspect screening study in samples from city areas in the Nordic countries. In contrast to target analysis, suspect screening starts with a general sample preparation and identification including as much compounds as possible. The resulting list of recorded compounds will be identified by comparison with a list of suspected compounds. Suspect screening has shown to be very useful for identification of emerging environmental pollutants. It was possible to identify: Perfluorinated compounds (PFC), chlorinated and brominated compounds, flame retardants, bisphenols, polycyclic aromatic compounds (PAC), industrial additives, and pharmaceuticals and personal care products (PPCP). This study was jointly performed by NILU, NIVA, and Umeå University on behalf of the Nordic Council of Ministers. The study was supervised by the Nordic screening group.
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12.
  • Schulze, Bastian, et al. (författare)
  • Inter-laboratory mass spectrometry dataset based on passive sampling of drinking water for non-target analysis
  • 2021
  • Ingår i: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Non-target analysis (NTA) employing high-resolution mass spectrometry is a commonly applied approach for the detection of novel chemicals of emerging concern in complex environmental samples. NTA typically results in large and information-rich datasets that require computer aided (ideally automated) strategies for their processing and interpretation. Such strategies do however raise the challenge of reproducibility between and within different processing workflows. An effective strategy to mitigate such problems is the implementation of inter-laboratory studies (ILS) with the aim to evaluate different workflows and agree on harmonized/standardized quality control procedures. Here we present the data generated during such an ILS. This study was organized through the Norman Network and included 21 participants from 11 countries. A set of samples based on the passive sampling of drinking water pre and post treatment was shipped to all the participating laboratories for analysis, using one pre-defined method and one locally (i.e. in-house) developed method. The data generated represents a valuable resource (i.e. benchmark) for future developments of algorithms and workflows for NTA experiments.
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13.
  • Schymanski, Emma L, et al. (författare)
  • Non-target screening with high-resolution mass spectrometry : critical review using a collaborative trial on water analysis
  • 2015
  • Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Berlin/Heidelberg. - 1618-2642 .- 1618-2650. ; 407:21, s. 6237-6255
  • Forskningsöversikt (refereegranskat)abstract
    • In this article, a dataset from a collaborative non-target screening trial organised by the NORMAN Association is used to review the state-of-the-art and discuss future perspectives of non-target screening using high-resolution mass spectrometry in water analysis. A total of 18 institutes from 12 European countries analysed an extract of the same water sample collected from the River Danube with either one or both of liquid and gas chromatography coupled with mass spectrometry detection. This article focuses mainly on the use of high resolution screening techniques with target, suspect, and non-target workflows to identify substances in environmental samples. Specific examples are given to emphasise major challenges including isobaric and co-eluting substances, dependence on target and suspect lists, formula assignment, the use of retention information, and the confidence of identification. Approaches and methods applicable to unit resolution data are also discussed. Although most substances were identified using high resolution data with target and suspect-screening approaches, some participants proposed tentative non-target identifications. This comprehensive dataset revealed that non-target analytical techniques are already substantially harmonised between the participants, but the data processing remains time-consuming. Although the objective of a "fully-automated identification workflow" remains elusive in the short term, important steps in this direction have been taken, exemplified by the growing popularity of suspect screening approaches. Major recommendations to improve non-target screening include better integration and connection of desired features into software packages, the exchange of target and suspect lists, and the contribution of more spectra from standard substances into (openly accessible) databases.
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14.
  • Thomas, Kevin V, et al. (författare)
  • Comparing illicit drug use in 19 European cities through sewage analysis
  • 2012
  • Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 432, s. 432-439
  • Tidskriftsartikel (refereegranskat)abstract
    • The analysis of sewage for urinary biomarkers of illicit drugs is a promising and complementary approach for estimating the use of these substances in the general population. For the first time, this approach was simultaneously applied in 19 European cities, making it possible to directly compare illicit drug loads in Europe over a 1-week period. An inter-laboratory comparison study was performed to evaluate the analytical performance of the participating laboratories. Raw 24-hour composite sewage samples were collected from 19 European cities during a single week in March 2011 and analyzed for the urinary biomarkers of cocaine, amphetamine, ecstasy, methamphetamine and cannabis using in-house optimized and validated analytical methods. The load of each substance used in each city was back-calculated from the measured concentrations. The data show distinct temporal and spatial patterns in drug use across Europe. Cocaine use was higher in Western and Central Europe and lower in Northern and Eastern Europe. The extrapolated total daily use of cocaine in Europe during the study period was equivalent to 356kg/day. High per capita ecstasy loads were observed in Dutch cities, as well as in Antwerp and London. In general, cocaine and ecstasy loads were significantly elevated during the weekend compared to weekdays. Per-capita loads of methamphetamine were highest in Helsinki and Turku, Oslo and Budweis, while the per capita loads of cannabis were similar throughout Europe. This study shows that a standardized analysis for illicit drug urinary biomarkers in sewage can be applied to estimate and compare the use of these substances at local and international scales. This approach has the potential to deliver important information on drug markets (supply indicator).
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15.
  • van Nuijs, Alexander L. N., et al. (författare)
  • Multi-year inter-laboratory exercises for the analysis of illicit drugs and metabolites in wastewater : development of a quality control system
  • 2018
  • Ingår i: TrAC. Trends in analytical chemistry. - : Elsevier. - 0165-9936 .- 1879-3142. ; 103, s. 34-43
  • Forskningsöversikt (refereegranskat)abstract
    • Thirty-seven laboratories from 25 countries present the development of an inter-laboratory testing scheme for the analysis of seven illicit drug residues in standard solutions, tap- and wastewater. Almost 10 000 concentration values were evaluated: triplicates of up to five samples and 26 laboratories per year. The setup was substantially improved with experiences gained across the six repetitions (e.g. matrix type, sample conditions, spiking levels). From this, (pre-)analytical issues (e.g. pH adjustment, filtration) were revealed for specific analytes which resulted in formulation of best-practice protocols for inter-laboratory setup and analytical procedures. The results illustrate the effectiveness of the interlaboratory setup to assess laboratory performance in the framework of wastewater-based epidemiology. The exercise proved that measurements of laboratories were of high quality (>80% satisfactory results for six out of seven analytes) and that analytical follow-up is important to assist laboratories in improving robustness of wastewater-based epidemiology results.
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