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  • Niemi, MEK, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • 2019
  • Tidskriftsartikel (refereegranskat)
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9.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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12.
  • Abbafati, Cristiana, et al. (författare)
  • 2020
  • Tidskriftsartikel (refereegranskat)
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13.
  • Gutierrez, C. P., et al. (författare)
  • DES16C3cje : A low-luminosity, long-lived supernova
  • 2020
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 496:1, s. 95-110
  • Tidskriftsartikel (refereegranskat)abstract
    • We present DES16C3cje, a low-luminosity, long-lived type II supernova (SN II) at redshift 0.0618, detected by the Dark Energy Survey (DES). DES16C3cje is a unique SN. The spectra are characterized by extremely narrow photospheric lines corresponding to very low expansion velocities of less than or similar to 1500 km s(-1), and the light curve shows an initial peak that fades after 50 d before slowly rebrightening over a further 100 d to reach an absolute brightness of M-r similar to 15.5 mag. The decline rate of the late-time light curve is then slower than that expected from the powering by radioactive decay of Co-56, but is comparable to that expected from accretion power. Comparing the bolometric light curve with hydrodynamical models, we find that DES16C3cje can be explained by either (i) a low explosion energy (0.11 foe) and relatively large Ni-56 production of 0.075 M-circle dot from an similar to 15 M-circle dot red supergiant progenitor typical of other SNe II, or (ii) a relatively compact similar to 40 M-circle dot star, explosion energy of 1 foe, and 0.08 M-circle dot of Ni-56. Both scenarios require additional energy input to explain the late-time light curve, which is consistent with fallback accretion at a rate of similar to 0.5 x 10(-)(8) M-circle dot s(-1).
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14.
  • Smartt, S. J., et al. (författare)
  • A kilonova as the electromagnetic counterpart to a gravitational-wave source
  • 2017
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 551:7678, s. 75-
  • Tidskriftsartikel (refereegranskat)abstract
    • Gravitational waves were discovered with the detection of binary black-hole mergers(1) and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova(2-5). The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate(6). Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short.-ray burst(7,8). The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 +/- 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 +/- 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 +/- 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.
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15.
  • Tobias, Deirdre K, et al. (författare)
  • Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
  • 2023
  • Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
  • Forskningsöversikt (refereegranskat)abstract
    • Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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16.
  • Anderson, J. P., et al. (författare)
  • A nearby super-luminous supernova with a long pre-maximum plateau and strong C (II) features
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 620
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Super-luminous supernovae (SLSNe) are rare events defined as being significantly more luminous than normal terminal stellar explosions. The source of the additional power needed to achieve such luminosities is still unclear. Discoveries in the local Universe (i.e. z < 0.1) are scarce, but afford dense multi-wavelength observations. Additional low-redshift objects are therefore extremely valuable.Aims. We present early-time observations of the type I SLSN ASASSN-18km/SN 2018bsz. These data are used to characterise the event and compare to literature SLSNe and spectral models. Host galaxy properties are also analysed.Methods. Optical and near-IR photometry and spectroscopy were analysed. Early-time ATLAS photometry was used to constrain the rising light curve. We identified a number of spectral features in optical-wavelength spectra and track their time evolution. Finally, we used archival host galaxy photometry together with H( II )region spectra to constrain the host environment.Results. ASASSN-18km/SN 2018bsz is found to be a type I SLSN in a galaxy at a redshift of 0.0267 (111 Mpc), making it the lowest-redshift event discovered to date. Strong C- II lines are identified in the spectra. Spectral models produced by exploding a Wolf-Rayet progenitor and injecting a magnetar power source are shown to be qualitatively similar to ASASSN-18km/SN 2018bsz, contrary to most SLSNe-I that display weak or non-existent C (II) lines. ASASSN-18km/SN 2018bsz displays along, slowly rising, red plateau of >26 days, before a steeper, faster rise to maximum. The host has an absolute magnitude of -19.8 mag (r), a mass of M-* = 1.5(-0.33)(+0.08) x 10(9) M-circle dot, and a star formation rate of =0.50(-0.19)(+2.22) M-circle dot yr(-1). A nearby H (II) region has an oxygen abundance (O3N2) of 8.31 +/- 0.01 dex.
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17.
  • Valiente-Dobon, J. J., et al. (författare)
  • Lifetime Measurements of the Neutron-Rich N=30 Isotones Ca-50 and Sc-51: Orbital Dependence of Effective Charges in the fp Shell
  • 2009
  • Ingår i: Physical Review Letters. - 1079-7114. ; 102:24
  • Tidskriftsartikel (refereegranskat)abstract
    • The lifetimes of the first excited states of the N=30 isotones Ca-50 and Sc-51 have been determined using the Recoil Distance Doppler Shift method in combination with the CLARA-PRISMA spectrometers. This is the first time such a method is applied to measure lifetimes of neutron-rich nuclei populated via a multinucleon transfer reaction. This extends the lifetime knowledge beyond the f(7/2) shell closure and allows us to derive the effective proton and neutron charges in the fp shell near the doubly magic nucleus Ca-48, using large-scale, shell-model calculations. These results indicate an orbital dependence of the core polarization along the fp shell.
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18.
  • Axfors, Cathrine, et al. (författare)
  • Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
  • 2021
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I-2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.
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19.
  • Griswold, Max G., et al. (författare)
  • Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
  • 2018
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 392:10152, s. 1015-1035
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.Methods: Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.Findings: Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week.Interpretation: Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.
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20.
  • Pursiainen, M., et al. (författare)
  • SN 2018bsz : A Type I superluminous supernova with aspherical circumstellar material
  • 2022
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a spectroscopic analysis of the most nearby Type I superluminous supernova (SLSN-I), SN 2018bsz. The photometric evolution of SN 2018bsz has several surprising features, including an unusual pre-peak plateau and evidence for rapid formation of dust ≳200 d post-peak. We show here that the spectroscopic and polarimetric properties of SN 2018bsz are also unique. While its spectroscopic evolution closely resembles SLSNe-I, with early O II absorption and C II P Cygni profiles followed by Ca, Mg, Fe, and other O features, a multi-component Hα profile appearing at ∼30 d post-maximum is the most atypical. The Hα is at first characterised by two emission components, one at ∼+3000 km s−1 and a second at ∼ − 7500 km s−1, with a third, near-zero-velocity component appearing after a delay. The blue and central components can be described by Gaussian profiles of intermediate width (FWHM ∼ 2000–6000 km s−1), but the red component is significantly broader (FWHM ≳ 10 000 km s−1) and Lorentzian. The blue Hα component evolves towards a lower-velocity offset before abruptly fading at ∼ + 100 d post-maximum brightness, concurrently with a light curve break. Multi-component profiles are observed in other hydrogen lines, including Paβ, and in lines of Ca II and He I. Spectropolarimetry obtained before (10.2 d) and after (38.4 d) the appearance of the H lines shows a large shift on the Stokes Q – U plane consistent with SN 2018bsz undergoing radical changes in its projected geometry. Assuming the supernova is almost unpolarised at 10.2 d, the continuum polarisation at 38.4 d reaches P ∼ 1.8%, implying an aspherical configuration. We propose that the observed evolution of SN 2018bsz can be explained by highly aspherical, possibly disk-like, circumstellar material (CSM) with several emitting regions. After the supernova explosion, the CSM is quickly overtaken by the ejecta, but as the photosphere starts to recede, the different CSM regions re-emerge, producing the peculiar line profiles. Based on the first appearance of Hα, we can constrain the distance of the CSM to be less than ∼6.5 × 1015 cm (430 AU), or even lower (≲87 AU) if the pre-peak plateau is related to an eruption that created the CSM. The presence of CSM has been inferred previously for other SLSNe-I, both directly and indirectly. However, it is not clear whether the rare properties of SN 2018bsz can be generalised for SLSNe-I, for example in the context of pulsational pair instability, or whether they are the result of an uncommon evolutionary path, possibly involving a binary companion.
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21.
  • Gifford, W. A., et al. (författare)
  • Managerial leadership for research use in nursing and allied health care professions: a systematic review
  • 2018
  • Ingår i: Implementation Science. - : Springer Science and Business Media LLC. - 1748-5908. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Leadership by point-of-care and senior managers is increasingly recognized as critical to the acceptance and use of research evidence in practice. The purpose of this systematic review was to identify the leadership behaviours of managers that are associated with research use by clinical staff in nursing and allied health professionals. Methods: A mixed methods systematic review was performed. Eight electronic bibliographic databases were searched. Studies examining the association between leadership behaviours and nurses and allied health professionals' use of research were eligible for inclusion. Studies were excluded if leadership could not be clearly attributed to someone in a management position. Two reviewers independently screened abstracts, reviewed full-text articles, extracted data and performed quality assessments. Narrative synthesis was conducted. Results: The search yielded 7019 unique titles and abstracts after duplicates were removed. Three hundred five full-text articles were reviewed, and 31 studies reported in 34 articles were included. Methods used were qualitative (n = 19), cross-sectional survey (n = 9), and mixed methods (n = 3). All studies included nurses, and six also included allied health professionals. Twelve leadership behaviours were extracted from the data for point-of-care managers and ten for senior managers. Findings indicated that managers performed a diverse range of leadership behaviours that encompassed change-oriented, relation-oriented and task-oriented behaviours. The most commonly described behavior was support for the change, which involved demonstrating conceptual and operational commitment to research-based practices. Conclusions: This systematic review adds to the growing body of evidence that indicates that manager-staff dyads are influential in translating research evidence into action. Findings also reveal that leadership for research use involves change and task-oriented behaviours that influence the environmental milieu and the organisational infrastructure that supports clinical care. While findings explain how managers enact leadership for research use, we now require robust methodological studies to determine which behaviours are effective in enabling research use with nurses and allied health professionals for high-quality evidence-based care.
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22.
  • Kröll, T., et al. (författare)
  • Transfer Reactions on Neutron-rich Nuclei at REX-ISOLDE
  • 2009
  • Ingår i: AIP Conference Proceedings. - 1551-7616 .- 0094-243X. ; 1165, s. 363-368 461
  • Konferensbidrag (refereegranskat)abstract
    • We report on one- and two-neutron transfer reactions to study the single-particle properties of nuclei at the border of the "island of inversion". The (d,p)- and (t,p)-reactions in inverse kinematics on the neutron-rich isotope Mg-30, delivered as radioactive beam by the REX-ISOLDE facility, have been investigated. The outgoing protons have been detected and identified by a newly built array of Si detectors. The gamma-decay of excited states has been detected in coincidence by the MINIBALL array. First results for Mg-31 and from the search for the second, spherical, 0(+) state in Mg-32 are presented.
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23.
  • Mendham, Amy E., et al. (författare)
  • Sarcopenic Obesity in Africa: A Call for Diagnostic Methods and Appropriate Interventions
  • 2021
  • Ingår i: Frontiers in Nutrition. - : Frontiers Media S.A.. - 2296-861X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • This perspective aims to highlight the lack of current knowledge on sarcopenic obesity in Africa and to call for diagnostic methods and appropriate interventions. Sarcopenic obesity has been defined as obesity that occurs in combination with low muscle mass and function, which is typically evident in older adults. However, there has been no clear consensus on population-specific diagnostic criterion, which includes both gold-standard measures that can be used in a more advanced health care system, and surrogate measures that can be used in low-income settings with limited resources and funding. Importantly, low and middle-income countries (LMICs) across Africa are in an ongoing state of economic and social transition, which has contributed to an increase in the aging population, alongside the added burden of poverty, obesity, and associated co-morbidities. It is anticipated that alongside the increased prevalence of obesity, these countries will further experience an increase in age-related musculoskeletal diseases such as sarcopenia. The developmental origins of health and disease (DOHaD) approach will allow clinicians and researchers to consider developmental trajectories, and the influence of the environment, for targeting high-risk individuals and communities for treatment and/or prevention-based interventions that are implemented throughout all stages of the life course. Once a valid and reliable diagnostic criterion is developed, we can firstly assess the prevalence and burden of sarcopenic obesity in LMICs in Africa, and secondly, develop appropriate and sustainable interventions that target improved dietary and physical activity behaviors throughout the life course.
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24.
  • Mendham, Amy E., et al. (författare)
  • Understanding factors associated with sarcopenic obesity in older African women from a low-income setting : a cross-sectional analysis
  • 2021
  • Ingår i: BMC Geriatrics. - : BioMed Central. - 1471-2318. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: High rates of food insecurity, obesity and obesity-related comorbidities in ageing South African (SA) women may amplify the risk of developing sarcopenic obesity. This study aimed to investigate the prevalence and correlates of sarcopenic obesity and its diagnostic components [grip strength, appendicular skeletal muscle mass (ASM) and body mass index (BMI)] in older SA women from a low-income setting.Methods: This cross-sectional study recruited black SA women between the ages of 60–85 years (n = 122) from a low-income community. Testing included a fasting blood sample (markers of cardiometabolic risk, HIV), whole body and regional muscle and fat mass (dual-energy absorptiometry x-ray), anthropometry, blood pressure, functional movement tests, current medication use, demographic and health questionnaires, physical activity (PA; accelerometery), household food insecurity access scale, and a one-week quantified food frequency questionnaire. Foundation for the National Institutes of Health (FNIH) criteria (grip strength and ASM, adjusted for BMI) were used to classify sarcopenia. Participants with sarcopenia alongside a BMI of > 30.0 kg/m2 were classified as having sarcopenic obesity. Prevalence using other criteria (European Working Group on Sarcopenia in Older People, Asian Working Group for Sarcopenia and the International Working Group for Sarcopenia) were also explored.Results: The prevalence of sarcopenia was 27.9%, which comprised of sarcopenia without obesity (3.3%) and sarcopenic obesity (24.6%). Other classification criteria showed that sarcopenia ranged from 0.8–14.7%, including 0.8–9.8% without obesity and 0–4.9% with sarcopenic obesity. Using multivariate-discriminant analysis (OPLS-DA) those with sarcopenic obesity presented with a descriptive profile of higher C-reactive protein, waist circumference, food security and sedentary time than women without sarcopenic obesity (p = 0.046). A similar profile described women with low BMI-adjusted grip strength (p < 0.001).Conclusions: The majority of women with sarcopenia were also obese (88%). We show a large discrepancy in the diagnostic criteria and the potential for significantly underestimating the prevalence of sarcopenia if BMI is not adjusted for. The main variables common to women with sarcopenic obesity were higher food security, lower PA and chronic inflammation. Our data highlights the importance of addressing obesity within these low-income communities to ensure the prevention of sarcopenic obesity and that quality of life is maintained with ageing.
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25.
  • Srivastav, Shubham, et al. (författare)
  • SN 2020kyg and the rates of faint Iax supernovae from ATLAS
  • 2022
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 511:2, s. 2708-2731
  • Tidskriftsartikel (refereegranskat)abstract
    • We present multiwavelength follow-up observations of the ATLAS discovered faint Iax supernova SN 2020kyg that peaked at an absolute magnitude of Mg ≈ −14.9 ± 0.2, making it another member of the faint Iax supernova population. The bolometric light curve requires only ≈7 × 10−3 M⊙ of radioactive 56Ni, with an ejected mass of Mej ∼ 0.4 M⊙ and a low kinetic energy of E ≈ 0.05 ± 0.02 × 1051 erg. We construct a homogeneous volume-limited sample of 902 transients observed by ATLAS within 100 Mpc during a 3.5 yr span. Using this sample, we constrain the rates of faint Iax (Mr ≳ −16) events within 60 Mpc at 12+14−8 per cent12−8+14 per cent of the SN Ia rate. The overall Iax rate, at 15+17−9 per cent15−9+17 per cent of the Ia rate, is dominated by the low-luminosity events, with luminous SNe Iax (Mr ≲ −17.5) like 2002cx and 2005hk, accounting for only 0.9+1.1−0.5 per cent0.9−0.5+1.1 per cent of the Ia rate (a 2σ upper limit of approximately 3 per cent). We favour the hybrid CONe WD + He star progenitor channel involving a failed deflagration of a near Chandrasekhar mass white dwarf, expected to leave a bound remnant and a surviving secondary companion, as a candidate explanation for faint Iax explosions. This scenario requires short delay times, consistent with the observed environments of SNe Iax. Furthermore, binary population synthesis calculations have suggested rates of 1−18 per cent1−18 per cent of the SN Ia rate for this channel, consistent with our rate estimates.
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26.
  • 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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27.
  • Allesøe, Rosa Lundbye, et al. (författare)
  • Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
  • 2023
  • Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
  • Tidskriftsartikel (refereegranskat)abstract
    • The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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28.
  • Angus-Dunne, Sarah J., et al. (författare)
  • Metallocene and organo-main group trifluoromethanesulfonates
  • 2006
  • Ingår i: Transition metal chemistry (Weinheim). - : Springer Science and Business Media LLC. - 0340-4285 .- 1572-901X. ; 31:2, s. 268-275
  • Tidskriftsartikel (refereegranskat)abstract
    • The substituted metallocene compounds Cp2M(OSO 2CF3)2 (Cp=η5-C 5H5; M = Ti, Zr, Hf, Nb, Mo), CpTi(OSO2CF 3)3 • 0.75(1,2-dimethoxyethane), and the organo-main group compounds (C6H5)3M′(OSO 2CF3) (M′=Si, Ge), (C6H5) 2Sn(OSO2CF3)2 and (C 6H5)3Sb(OSO2CF3) 2, were synthesized from the corresponding chloride or bromide compounds and silver trifluoromethanesulfonate (triflate) and characterized spectroscopically, including a detailed analysis of their IR spectra. Triflate coordination is typically monodentate, but CpTi(OSO2CF 3)3 • 0.75(1,2-dimethoxyethane) and the organo-germanium triflate show evidence of bidentate CF3SO 3 - ligands and are likely to have polymeric structures. Conductance measurements in nitromethane, acetone and acetonitrile have demonstrated the ease of triflate substitution, with a limited kinetic study of acetone solvation of the Ti and Hf compounds supporting an associative pathway. Three new catalysts for the polymerization of tetrahydrofuran, Cp 2HfCl2/Ag(OSO2CF3), CpTiCl 3/Ag(OSO2CF3) and (C6H 5)2SiCl2/Ag(OSO2CF3), are also reported.
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29.
  • Atabaki-Pasdar, Naeimeh, et al. (författare)
  • Inferring causal pathways between metabolic processes and liver fat accumulation: an IMI DIRECT study
  • 2021
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) often co-occur. Defining causal pathways underlying this relationship may help optimize the prevention and treatment of both diseases. Thus, we assessed the strength and magnitude of the putative causal pathways linking dysglycemia and fatty liver, using a combination of causal inference methods.Measures of glycemia, insulin dynamics, magnetic resonance imaging (MRI)-derived abdominal and liver fat content, serological biomarkers, lifestyle, and anthropometry were obtained in participants from the IMI DIRECT cohorts (n=795 with new onset T2D and 2234 individuals free from diabetes). UK Biobank (n=3641) was used for modelling and replication purposes. Bayesian networks were employed to infer causal pathways, with causal validation using two-sample Mendelian randomization.Bayesian networks fitted to IMI DIRECT data identified higher basal insulin secretion rate (BasalISR) and MRI-derived excess visceral fat (VAT) accumulation as the features of dysmetabolism most likely to cause liver fat accumulation; the unconditional probability of fatty liver (>5%) increased significantly when conditioning on high levels of BasalISR and VAT (by 23%, 32% respectively; 40% for both). Analyses in UK Biobank yielded comparable results. MR confirmed most causal pathways predicted by the Bayesian networks.Here, BasalISR had the highest causal effect on fatty liver predisposition, providing mechanistic evidence underpinning the established association of NAFLD and T2D. BasalISR may represent a pragmatic biomarker for NAFLD prediction in clinical practice.Competing Interest StatementHR is an employee and shareholder of Sanofi. MIM: The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. MIM has served on advisory panels for Pfizer, NovoNordisk and Zoe Global, has received honoraria from Merck, Pfizer, Novo Nordisk and Eli Lilly, and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda. As of June 2019, MIM is an employee of Genentech, and a holder of Roche stock. AM is a consultant for Lilly and has received research grants from several diabetes drug companies. PWF has received research grants from numerous diabetes drug companies and fess as consultant from Novo Nordisk, Lilly, and Zoe Global Ltd. He is currently the Scientific Director in Patient Care at the Novo Nordisk Foundation. Other authors declare non competing interests.Funding StatementThe work leading to this publication has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement 115317 (DIRECT) resources of which are composed of financial contribution from the European Union Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. NAP is supported in part by Henning och Johan Throne-Holsts Foundation, Hans Werthen Foundation, an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. HPM is supported by an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. AGJ is supported by an NIHR Clinician Scientist award (17/0005624). RK is funded by the Novo Nordisk Foundation (NNF18OC0031650) as part of a postdoctoral fellowship, an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. AK, PM, HF, JF and GNG are supported by an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. TJM is funded by an NIHR clinical senior lecturer fellowship. S.Bru acknowledges support from the Novo Nordisk Foundation (grants NNF17OC0027594 and NNF14CC0001). ATH is a Wellcome Trust Senior Investigator and is also supported by the NIHR Exeter Clinical Research Facility. JMS acknowledges support from Science for Life Laboratory (Plasma Profiling Facility), Knut and Alice Wallenberg Foundation (Human Protein Atlas) and Erling-Persson Foundation (KTH Centre for Precision Medicine). MIM is supported by the following grants; Wellcome (090532, 098381, 106130, 203141, 212259); NIH (U01-DK105535). PWF is supported by an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Approval for the study protocol was obtained from each of the regional research ethics review boards separately (Lund, Sweden: 20130312105459927, Copenhagen, Denmark: H-1-2012-166 and H-1-2012-100, Amsterdam, Netherlands: NL40099.029.12, Newcastle, Dundee and Exeter, UK: 12/NE/0132), and all participants provided written informed consent at enrolment. The research conformed to the ethical principles for medical research involving human participants outlined in the Declaration of Helsinki.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAuthors agree to make data and materials supporting the results or analyses presented in their paper available upon reasonable request
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30.
  • Bass, Gary Alan, 1979-, et al. (författare)
  • Techniques for mesoappendix transection and appendix resection: insights from the ESTES SnapAppy study
  • 2023
  • Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Science and Business Media LLC. - 1863-9933 .- 1615-3146 .- 1863-9941. ; 49, s. 17-32
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Surgically managed appendicitis exhibits great heterogeneity in techniques for mesoappendix transection and appendix amputation from its base. It is unclear whether a particular surgical technique provides outcome benefit or reduces complications. Material and methods: We undertook a pre-specified subgroup analysis of all patients who underwent laparoscopic appendectomy at index admission during SnapAppy (ClinicalTrials.gov Registration: NCT04365491). We collected routine, anonymized observational data regarding surgical technique, patient demographics and indices of disease severity, without change to clinical care pathway or usual surgeon preference. Outcome measures of interest were the incidence of complications, unplanned reoperation, readmission, admission to the ICU, death, hospital length of stay, and procedure duration. We used Poisson regression models with robust standard errors to calculate incident rate ratios (IRRs) and 95% confidence intervals (CIs). Results: Three-thousand seven hundred sixty-eight consecutive adult patients, included from 71 centers in 14 countries, were followed up from date of admission for 90days. The mesoappendix was divided hemostatically using electrocautery in 1564(69.4%) and an energy device in 688(30.5%). The appendix was amputated by division of its base between looped ligatures in 1379(37.0%), with a stapler in 1421(38.1%) and between clips in 929(24.9%). The technique for securely dividing the appendix at its base in acutely inflamed (AAST Grade 1) appendicitis was equally divided between division between looped ligatures, clips and stapled transection. However, the technique used differed in complicated appendicitis (AAST Grade 2 +) compared with uncomplicated (Grade 1), with a shift toward transection of the appendix base by stapler (58% vs. 38%; p < 0.001). While no statistical difference in outcomes could be detected between different techniques for division of appendix base, decreased risk of any [adjusted IRR (95% CI): 0.58 (0.41–0.82), p = 0.002] and severe [adjusted IRR (95% CI): 0.33 (0.11–0.96), p = 0.045] complications could be detected when using energy devices. Conclusions: Safe mesoappendix transection and appendix resection are accomplished using heterogeneous techniques. Technique selection for both mesoappendix transection and appendix resection correlates with AAST grade. Higher grade led to more ultrasonic tissue transection and stapled appendix resection. Higher AAST appendicitis grade also correlated with infection-related complication occurrence. Despite the overall well-tolerated heterogeneity of approaches to acute appendicitis, increasing disease acuity or complexity appears to encourage homogeneity of intraoperative surgical technique toward advanced adjuncts.
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31.
  • Besser, Rachel E J, et al. (författare)
  • Urine C-Peptide Creatinine Ratio Is a Noninvasive Alternative to the Mixed-Meal Tolerance Test in Children and Adults With Type 1 Diabetes
  • 2011
  • Ingår i: DIABETES CARE. - : American Diabetes Association Inc. - 0149-5992 .- 1935-5548. ; 34:3, s. 607-609
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE-Stimulated serum C-peptide (sCP) during a mixed-meal tolerance test (MMTT) is the gold standard measure of endogenous insulin secretion, but practical issues limit its use. We assessed urine C-peptide creatinine ratio (UCPCR) as an alternative. RESEARCH DESIGN AND METHODS-Seventy-two type 1 diabetic patients (age of diagnosis median 14 years [interquartile range 10-22]; diabetes duration 6.5[2.3-32.7]) had an MMTT. sCP was collected at 90 min. Urine for UCPCR was collected at 120 min and following a home evening meal. RESULTS-MMTT 120-min UCPCR was highly correlated to 90-min sCP (r = 0.97; P andlt; 0.0001). UCPCR andgt;= 0.53 nmol/mmol had 94% sensitivity/100% specificity for significant endogenous insulin secretion (90-min sCP andgt;= 0.2 nmol/L). The 120-min postprandial evening meal UCPCR was highly correlated to 90-min sCP (r = 0.91; P andlt; 0.0001). UCPCR andgt;= 0.37 nmol/mmol had 84% sensitivity/97% specificity for sCP andgt;= 0.2 nmol/L. CONCLUSIONS-UCPCR testing is a sensitive and specific method for detecting insulin secretion. UCPCR may be a practical alternative to serum C-peptide testing, avoiding the need for inpatient investigation.
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32.
  • Bizzotto, Roberto, et al. (författare)
  • Processes Underlying Glycemic Deterioration in Type 2 Diabetes : An IMI DIRECT Study
  • 2021
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 44:2, s. 511-518
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: We investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: A total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), β-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA1c deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression. RESULTS: Faster HbA1c progression was independently associated with faster deterioration of OGIS and GS and increasing CLIm; visceral or liver fat, HDL-cholesterol, and triglycerides had further independent, though weaker, roles (R2 = 0.38). A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from area under the receiver operating characteristic = 0.94). The proportion of fast progressors was reduced from 56% to 8-10% in subgroups in which only one trait among OGIS, GS, and CLIm was relatively stable (odds ratios 0.07-0.09). T2D polygenic risk score and baseline pancreatic fat, glucagon-like peptide 1, glucagon, diet, and physical activity did not show an independent role. CONCLUSIONS: Deteriorating insulin sensitivity and β-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of patients with T2D in the initial phase of the disease. Stabilization of a single trait among insulin sensitivity, β-cell function, and insulin clearance may be relevant to prevent progression.
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33.
  • Brem, Jürgen, et al. (författare)
  • Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors
  • 2022
  • Ingår i: Nature Chemistry. - : Springer Nature. - 1755-4330 .- 1755-4349. ; 14:1, s. 15-24
  • Tidskriftsartikel (refereegranskat)abstract
    • Carbapenems are vital antibiotics, but their efficacy is increasingly compromised by metallo-β-lactamases (MBLs). Here we report the discovery and optimization of potent broad-spectrum MBL inhibitors. A high-throughput screen for NDM-1 inhibitors identified indole-2-carboxylates (InCs) as potential β-lactamase stable β-lactam mimics. Subsequent structure-activity relationship studies revealed InCs as a new class of potent MBL inhibitor, active against all MBL classes of major clinical relevance. Crystallographic studies revealed a binding mode of the InCs to MBLs that, in some regards, mimics that predicted for intact carbapenems, including with respect to maintenance of the Zn(II)-bound hydroxyl, and in other regards mimics binding observed in MBL-carbapenem product complexes. InCs restore carbapenem activity against multiple drug-resistant Gram-negative bacteria and have a low frequency of resistance. InCs also have a good in vivo safety profile, and when combined with meropenem show a strong in vivo efficacy in peritonitis and thigh mouse infection models.
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34.
  • Carrieri, Daniele, et al. (författare)
  • Recontacting patients in clinical genetics services : recommendations of the European Society of Human Genetics
  • 2019
  • Ingår i: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 27:2, s. 169-182
  • Tidskriftsartikel (refereegranskat)abstract
    • Technological advances have increased the availability of genomic data in research and the clinic. If, over time, interpretation of the significance of the data changes, or new information becomes available, the question arises as to whether recontacting the patient and/or family is indicated. The Public and Professional Policy Committee of the European Society of Human Genetics (ESHG), together with research groups from the UK and the Netherlands, developed recommendations on recontacting which, after public consultation, have been endorsed by ESHG Board. In clinical genetics, recontacting for updating patients with new, clinically significant information related to their diagnosis or previous genetic testing may be justifiable and, where possible, desirable. Consensus about the type of information that should trigger recontacting converges around its clinical and personal utility. The organization of recontacting procedures and policies in current health care systems is challenging. It should be sustainable, commensurate with previously obtained consent, and a shared responsibility between healthcare providers, laboratories, patients, and other stakeholders. Optimal use of the limited clinical resources currently available is needed. Allocation of dedicated resources for recontacting should be considered. Finally, there is a need for more evidence, including economic and utility of information for people, to inform which strategies provide the most cost-effective use of healthcare resources for recontacting.
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35.
  • Davison, Lucy J, et al. (författare)
  • Long-range DNA looping and gene expression analyses identify DEXI as an autoimmune disease candidate gene
  • 2012
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:2, s. 322-333
  • Tidskriftsartikel (refereegranskat)abstract
    • The chromosome 16p13 region has been associated with several autoimmune diseases, including type 1 diabetes (T1D) and multiple sclerosis (MS). CLEC16A has been reported as the most likely candidate gene in the region, since it contains the most disease-associated single-nucleotide polymorphisms (SNPs), as well as an imunoreceptor tyrosine-based activation motif. However, here we report that intron 19 of CLEC16A, containing the most autoimmune disease-associated SNPs, appears to behave as a regulatory sequence, affecting the expression of a neighbouring gene, DEXI. The CLEC16A alleles that are protective from T1D and MS are associated with increased expression of DEXI, and no other genes in the region, in two independent monocyte gene expression data sets. Critically, using chromosome conformation capture (3C), we identified physical proximity between the DEXI promoter region and intron 19 of CLEC16A, separated by a loop of >150 kb. In reciprocal experiments, a 20 kb fragment of intron 19 of CLEC16A, containing SNPs associated with T1D and MS, as well as with DEXI expression, interacted with the promotor region of DEXI but not with candidate DNA fragments containing other potential causal genes in the region, including CLEC16A. Intron 19 of CLEC16A is highly enriched for transcription-factor-binding events and markers associated with enhancer activity. Taken together, these data indicate that although the causal variants in the 16p13 region lie within CLEC16A, DEXI is an unappreciated autoimmune disease candidate gene, and illustrate the power of the 3C approach in progressing from genome-wide association studies results to candidate causal genes.
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36.
  • Dawe, H., et al. (författare)
  • D-methionine interferes with non-typeable Haemophilus influenzae peptidoglycan synthesis during growth and biofilm formation
  • 2017
  • Ingår i: Microbiology-Sgm. - : Microbiology Society. - 1350-0872. ; 163:7, s. 1093-1104
  • Tidskriftsartikel (refereegranskat)abstract
    • Non-typeable Haemophilus influenzae (NTHi) is an opportunistic pathogen that plays a major role in a number of respiratory tract infections, including otitis media, cystic fibrosis and chronic obstructive pulmonary disease. Biofilm formation has been implicated in both NTHi colonization and disease, and is responsible for the increased tolerance of this pathogen towards antibiotic treatment. Targeting metabolic pathways that are important in NTHi biofilm formation represents a potential strategy to combat this antibiotic recalcitrance. A previous investigation demonstrated increased expression of a putative D-methionine uptake protein following exposure of NTHi biofilms to the ubiquitous signalling molecule, nitric oxide. We therefore hypothesized that treatment with exogenous D-methionine would impact on NTHi biofilm formation and increase antibiotic sensitivity. Treatment of NTHi during the process of biofilm formation resulted in a reduction in biofilm viability, increased biomass, changes in the overall biofilm architecture and the adoption of an amorphous cellular morphology. Quantitative proteomic analyses identified 124 proteins that were differentially expressed following D-methionine treatment, of which 51 (41 %) were involved in metabolic and transport processes. Nine proteins involved in peptidoglycan synthesis and cell division showed significantly increased expression. Furthermore, D-methionine treatment augmented the efficacy of azithromycin treatment and highlighted the potential of D-methionine as an adjunctive therapeutic approach for NTHi biofilm-associated infections.
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37.
  • Dawed, Adem Y., et al. (författare)
  • Pharmacogenomics of GLP-1 receptor agonists : a genome- wide analysis of observational data and large randomised controlled trials
  • 2023
  • Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 11:1, s. 33-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In the treatment of type 2 diabetes, GLP-1 receptor agonists lower blood glucose concentrations, body weight, and have cardiovascular benefits. The efficacy and side effects of GLP-1 receptor agonists vary between people. Human pharmacogenomic studies of this inter-individual variation can provide both biological insight into drug action and provide biomarkers to inform clinical decision making. We therefore aimed to identify genetic variants associated with glycaemic response to GLP-1 receptor agonist treatment. Methods:In this genome-wide analysis we included adults (aged & GE;18 years) with type 2 diabetes treated with GLP-1 receptor agonists with baseline HbA1c of 7% or more (53 mmol/mol) from four prospective observational cohorts (DIRECT, PRIBA, PROMASTER, and GoDARTS) and two randomised clinical trials (HARMONY phase 3 and AWARD). The primary endpoint was HbA1c reduction at 6 months after starting GLP-1 receptor agonists. We evaluated variants in GLP1R, then did a genome-wide association study and gene-based burden tests. Findings:4571 adults were included in our analysis, of these, 3339 (73%) were White European, 449 (10%) Hispanic, 312 (7%) American Indian or Alaskan Native, and 471 (10%) were other, and around 2140 (47%) of the participants were women. Variation in HbA1c reduction with GLP-1 receptor agonists treatment was associated with rs6923761G & RARR;A (Gly168Ser) in the GLP1R (0.08% [95% CI 0.04-0.12] or 0.9 mmol/mol lower reduction in HbA1c per serine, p=6.0 x 10-5) and low frequency variants in ARRB1 (optimal sequence kernel association test p=6.7 x 10-8), largely driven by rs140226575G & RARR;A (Thr370Met; 0.25% [SE 0.06] or 2.7 mmol/mol [SE 0.7] greater HbA1c reduction per methionine, p=5.2 x 10-6). A similar effect size for the ARRB1 Thr370Met was seen in Hispanic and American Indian or Alaska Native populations who have a higher frequency of this variant (6-11%) than in White European populations. Combining these two genes identified 4% of the population who had a 30% greater reduction in HbA1c than the 9% of the population with the worse response. Interpretation:This genome-wide pharmacogenomic study of GLP-1 receptor agonists provides novel biological and clinical insights. Clinically, when genotype is routinely available at the point of prescribing, individuals with ARRB1 variants might benefit from earlier initiation of GLP-1 receptor agonists.
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38.
  • Dreinhofer, Karsten E, et al. (författare)
  • Multinational survey of osteoporotic fracture management
  • 2005
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 16:Suppl. 2, s. 44-53
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoporosis is characterized by a decreased bone mass and an increased bone fragility and susceptibility to fracture. Patients with a fragility fracture at any site have an increased risk of sustaining future fractures. Orthopedic surgeons manage most of these fractures and are often the only physician seen by the patient. Mounting evidence that orthopedic surgeons are not well attuned to osteoporosis led the Bone and Joint Decade (BJD) and the International Osteoporosis Foundation (IOF) to survey 3,422 orthopedic surgeons in France, Germany, Italy, Spain, the United Kingdom, and New Zealand. The majority of the respondents in all countries had the opinion that the orthopedic surgeon should identify and initiate the assessment of osteoporosis in patients with fragility fractures. Heterogeneous practice pattern exist in different countries; however, identification and treatment of the osteoporotic patient seems to be insufficient in many areas: half of the orthopedic surgeons surveyed received little or no training in osteoporosis. Only approximately one in four orthopedic surgeons in France, the UK and New Zealand regarded themselves as knowledgeable about treatment modalities. Less than one-fifth of the orthopedic surgeons arranged for a surgically treated patient with a fragility fracture to have a bone mineral density (BMD) test. Twenty percent said that they never refer a patient after a fragility fracture for BMD. Only half of the orthopedic surgeons in southern Europe know about the importance of some external risk factors for hip fractures (cataracts, poor lighting, pathway obstacles, poor balance). In summary, this survey clearly indicates that many orthopedic surgeons still neglect to identify, assess and treat patients with fragility fractures for osteoporosis. More educational opportunities need to be offered to orthopedic surgeons through articles, web-based learning and educational seminars. Development of a simple clinical pathway from evidence-based guidelines is an important step to ensure that optimal care is provided for patients with fragility fractures.
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39.
  • Engel, Philipp, et al. (författare)
  • The Bee Microbiome: Impact on Bee Health and Model for Evolution and Ecology of Host-Microbe Interactions
  • 2016
  • Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 7:2
  • Forskningsöversikt (refereegranskat)abstract
    • As pollinators, bees are cornerstones for terrestrial ecosystem stability and key components in agricultural productivity. All animals, including bees, are associated with a diverse community of microbes, commonly referred to as the micro biome. The bee micro biome is likely to be a crucial factor affecting host health. However, with the exception of a few pathogens, the impacts of most members of the bee microbiome on host health are poorly understood. Further, the evolutionary and ecological forces that shape and change the microbiome are unclear. Here, we discuss recent progress in our understanding of the bee microbiome, and we present challenges associated with its investigation. We conclude that global coordination of research efforts is needed to fully understand the complex and highly dynamic nature of the interplay between the bee micro biome, its host, and the environment. High-throughput sequencing technologies are ideal for exploring complex biological systems, including host-microbe interactions. To maximize their value and to improve assessment of the factors affecting bee health, sequence data should be archived, curated, and analyzed in ways that promote the synthesis of different studies. To this end, the BeeBiome consortium aims to develop an online database which would provide reference sequences, archive metadata, and host analytical resources. The goal would be to support applied and fundamental research on bees and their associated microbes and to provide a collaborative framework for sharing primary data from different research programs, thus furthering our understanding of the bee microbiome and its impact on pollinator health.
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40.
  • Eriksen, Rebeca, et al. (författare)
  • Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk : An IMI DIRECT study
  • 2020
  • Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 58
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Dietary advice remains the cornerstone of prevention and management of type 2 diabetes (T2D). However, understanding the efficacy of dietary interventions is confounded by the challenges inherent in assessing free living diet. Here we profiled dietary metabolites to investigate glycaemic deterioration and cardiometabolic risk in people at risk of or living with T2D. Methods: We analysed data from plasma collected at baseline and 18-month follow-up in individuals from the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohort 1 n = 403 individuals with normal or impaired glucose regulation (prediabetic) and cohort 2 n = 458 individuals with new onset of T2D. A dietary metabolite profile model (Tpred) was constructed using multivariable regression of 113 plasma metabolites obtained from targeted metabolomics assays. The continuous Tpred score was used to explore the relationships between diet, glycaemic deterioration and cardio-metabolic risk via multiple linear regression models. Findings: A higher Tpred score was associated with healthier diets high in wholegrain (β=3.36 g, 95% CI 0.31, 6.40 and β=2.82 g, 95% CI 0.06, 5.57) and lower energy intake (β=-75.53 kcal, 95% CI -144.71, -2.35 and β=-122.51 kcal, 95% CI -186.56, -38.46), and saturated fat (β=-0.92 g, 95% CI -1.56, -0.28 and β=–0.98 g, 95% CI -1.53, -0.42 g), respectively for cohort 1 and 2. In both cohorts a higher Tpred score was also associated with lower total body adiposity and favourable lipid profiles HDL-cholesterol (β=0.07 mmol/L, 95% CI 0.03, 0.1), (β=0.08 mmol/L, 95% CI 0.04, 0.1), and triglycerides (β=-0.1 mmol/L, 95% CI -0.2, -0.03), (β=-0.2 mmol/L, 95% CI -0.3, -0.09), respectively for cohort 1 and 2. In cohort 2, the Tpred score was negatively associated with liver fat (β=-0.74%, 95% CI -0.67, -0.81), and lower fasting concentrations of HbA1c (β=-0.9 mmol/mol, 95% CI -1.5, -0.1), glucose (β=-0.2 mmol/L, 95% CI -0.4, -0.05) and insulin (β=-11.0 pmol/mol, 95% CI -19.5, -2.6). Longitudinal analysis showed at 18-month follow up a higher Tpred score was also associated lower total body adiposity in both cohorts and lower fasting glucose (β=-0.2 mmol/L, 95% CI -0.3, -0.01) and insulin (β=-9.2 pmol/mol, 95% CI -17.9, -0.4) concentrations in cohort 2. Interpretation: Plasma dietary metabolite profiling provides objective measures of diet intake, showing a relationship to glycaemic deterioration and cardiometabolic health. Funding: This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115,317 (DIRECT), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007–2013) and EFPIA companies.
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41.
  • Forssten, Maximilian Peter, 1996-, et al. (författare)
  • Surgical management of acute appendicitis during the European COVID-19 second wave: safe and effective
  • 2023
  • Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Science and Business Media LLC. - 1863-9933 .- 1615-3146 .- 1863-9941. ; 49, s. 57-67
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The COVID-19 (SARS-CoV-2) pandemic drove acute care surgeons to pivot from long established practice patterns. Early safety concerns regarding increased postoperative complication risk in those with active COVID infection promoted antibiotic-driven non-operative therapy for select conditions ahead of an evidence-base. Our study assesses whether active or recent SARS-CoV-2 positivity increases hospital length of stay (LOS) or postoperative complications following appendectomy. Methods: Data were derived from the prospective multi-institutional observational SnapAppy cohort study. This preplanned data analysis assessed consecutive patients aged ≥ 15years who underwent appendectomy for appendicitis (November 2020–May 2021). Patients were categorized based on SARS-CoV-2 seropositivity: no infection, active infection, and prior infection. Appendectomy method, LOS, and complications were abstracted. The association between SARS-CoV-2 seropositivity and complications was determined using Poisson regression, while the association with LOS was calculated using a quantile regression model. Results: Appendectomy for acute appendicitis was performed in 4047 patients during the second and third European COVID waves. The majority were SARS-CoV-2 uninfected (3861, 95.4%), while 70 (1.7%) were acutely SARS-CoV-2 positive, and 116 (2.8%) reported prior SARS-CoV-2 infection. After confounder adjustment, there was no statistically significant association between SARS-CoV-2 seropositivity and LOS, any complication, or severe complications. Conclusion: During sequential SARS-CoV-2 infection waves, neither active nor prior SARS-CoV-2 infection was associated with prolonged hospital LOS or postoperative complication. Despite early concerns regarding postoperative safety and outcome during active SARS-CoV-2 infection, no such association was noted for those with appendicitis who underwent operative management.
  •  
42.
  • Gifford, Wendy A, et al. (författare)
  • Managerial leadership for research use in nursing and allied health care professions : a narrative synthesis protocol
  • 2014
  • Ingår i: Systematic Reviews. - : BioMed Central. - 2046-4053. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Nurses and allied health care professionals (physiotherapists, occupational therapists, speech and language pathologists, dietitians) form more than half of the clinical health care workforce and play a central role in health service delivery. There is a potential to improve the quality of health care if these professionals routinely use research evidence to guide their clinical practice. However, the use of research evidence remains unpredictable and inconsistent. Leadership is consistently described in implementation research as critical to enhancing research use by health care professionals. However, this important literature has not yet been synthesized and there is a lack of clarity on what constitutes effective leadership for research use, or what kinds of intervention effectively develop leadership for the purpose of enabling and enhancing research use in clinical practice. We propose to synthesize the evidence on leadership behaviours amongst front line and senior managers that are associated with research evidence by nurses and allied health care professionals, and then determine the effectiveness of interventions that promote these behaviours.Methods/design: Using an integrated knowledge translation approach that supports a partnership between researchers and knowledge users throughout the research process, we will follow principles of knowledge synthesis using a systematic method to synthesize different types of evidence involving: searching the literature, study selection, data extraction and quality assessment, and analysis. A narrative synthesis will be conducted to explore relationships within and across studies and meta-analysis will be performed if sufficient homogeneity exists across studies employing experimental randomized control trial designs.DISCUSSION: With the engagement of knowledge users in leadership and practice, we will synthesize the research from a broad range of disciplines to understand the key elements of leadership that supports and enables research use by health care practitioners, and how to develop leadership for the purpose of enhancing research use in clinical practice.
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43.
  • Gonzalez, Maria Camila, et al. (författare)
  • Cognitive and motor decline in dementia with lewy bodies and Parkinson's disease dementia
  • 2023
  • Ingår i: Movement Disorders Clinical Practice. - : John Wiley & Sons. - 2330-1619. ; 10:6, s. 980-986
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is a need to better understand the rate of cognitive and motor decline of Dementia with Lewy bodies (DLB) and Parkinson's disease Dementia (PDD).Objectives: To compare the rate of cognitive and motor decline in patients with DLB and PDD from the E-DLB Consortium and the Parkinson's Incidence Cohorts Collaboration (PICC) Cohorts.Methods: The annual change in MMSE and MDS-UPDRS part III was estimated using linear mixed regression models in patients with at least one follow-up (DLB n = 837 and PDD n = 157).Results: When adjusting for confounders, we found no difference in the annual change in MMSE between DLB and PDD (−1.8 [95% CI −2.3, −1.3] vs. −1.9 [95% CI −2.6, −1.2] [P = 0.74]). MDS-UPDRS part III showed nearly identical annual changes (DLB 4.8 [95% CI 2.1, 7.5]) (PDD 4.8 [95% CI 2.7, 6.9], [P = 0.98]).Conclusions: DLB and PDD showed similar rates of cognitive and motor decline. This is relevant for future clinical trial designs.
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44.
  • Goodman, Matthew O., et al. (författare)
  • Causal Association Between Subtypes of Excessive Daytime Sleepiness and Risk of Cardiovascular Diseases
  • 2023
  • Ingår i: Journal of the American Heart Association. - 2047-9980. ; 12:24
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Excessive daytime sleepiness (EDS), experienced in 10% to 20% of the population, has been associated with cardiovascular disease and death. However, the condition is heterogeneous and is prevalent in individuals having short and long sleep duration. We sought to clarify the relationship between sleep duration subtypes of EDS with cardiovascular outcomes, accounting for these subtypes. METHODS AND RESULTS: We defined 3 sleep duration subtypes of excessive daytime sleepiness: normal (6-9hours), short (<6hours), and long (>9hours), and compared these with a nonsleepy, normal-sleep-duration reference group. We analyzed their associations with incident myocardial infarction (MI) and stroke using medical records of 355901 UK Biobank participants and performed 2-sample Mendelian randomization for each outcome. Compared with healthy sleep, long-sleep EDS was associated with an 83% increased rate of MI (hazard ratio, 1.83 [95% CI, 1.21-2.77]) during 8.2-year median follow-up, adjusting for multiple health and sociodemographic factors. Mendelian randomization analysis provided supporting evidence of a causal role for a genetic long-sleep EDS subtype in MI (inverse-variance weighted β=1.995, P=0.001). In contrast, we did not find evidence that other subtypes of EDS were associated with incident MI or any associations with stroke (P>0.05). CONCLUSIONS: Our study suggests the previous evidence linking EDS with increased cardiovascular disease risk may be primarily driven by the effect of its long-sleep subtype on higher risk of MI. Underlying mechanisms remain to be investigated but may involve sleep irregularity and circadian disruption, suggesting a need for novel interventions in this population.
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45.
  • Lau, Angus, et al. (författare)
  • alpha-Synuclein strains target distinct brain regions and cell types
  • 2020
  • Ingår i: Nature Neuroscience. - : NATURE PUBLISHING GROUP. - 1097-6256 .- 1546-1726. ; 23, s. 21-31
  • Tidskriftsartikel (refereegranskat)abstract
    • The clinical and pathological differences between synucleinopathies such as Parkinson's disease and multiple system atrophy have been postulated to stem from unique strains of alpha-synuclein aggregates, akin to what occurs in prion diseases. Here we demonstrate that inoculation of transgenic mice with different strains of recombinant or brain-derived alpha-synuclein aggregates produces clinically and pathologically distinct diseases. Strain-specific differences were observed in the signs of neurological illness, time to disease onset, morphology of cerebral alpha-synuclein deposits and the conformational properties of the induced aggregates. Moreover, different strains targeted distinct cellular populations and cell types within the brain, recapitulating the selective targeting observed among human synucleinopathies. Strain-specific clinical, pathological and biochemical differences were faithfully maintained after serial passaging, which implies that alpha-synuclein propagates via prion-like conformational templating. Thus, pathogenic alpha-synuclein exhibits key hallmarks of prion strains, which provides evidence that disease heterogeneity among the synucleinopathies is caused by distinct alpha-synuclein strains.
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46.
  • Makgae, Ofentse A., et al. (författare)
  • Atomic Structure and Valence State of Cobalt Nanocrystals on Carbon under Syngas Versus Hydrogen Reduction
  • 2022
  • Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 126:14, s. 6325-6333
  • Tidskriftsartikel (refereegranskat)abstract
    • The composition of the reducing gas in the activation of Co Fischer-Tropsch synthesis catalysts determines the nature of the catalytically active Co species. This study reports on the effect of H2versus syngas (H2/CO = 2) on the reducibility of Co3O4nanoparticles supported on hollow carbon spheres, using ex situ and in situ high-resolution aberration-corrected analytical electron microscopy. High-resolution images revealed twinned fcc Co particles encapsulated in carbon from syngas treatment while H2-treated particles were mostly CoO. Moreover, the electron energy loss of the Co-L3,2and O-K edge fine structures show improved reducibility in syngas than in H2at 350 °C. The effect of high temperature on the reducibility of the Co3O4nanoparticles is also explored. Carbon fiber encapsulation of twinned fcc Co particles observed during the syngas treatment provides sinter resistance at high temperatures. Both ex situ and in situ results indicate that syngas activation is efficient for obtaining highly reduced Co nanoparticles at lower temperatures.
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47.
  • Maple-Grødem, Jodi, et al. (författare)
  • Association of GBA Genotype With Motor and Functional Decline in Patients With Newly Diagnosed Parkinson Disease
  • 2021
  • Ingår i: Neurology. - : aan. - 0028-3878 .- 1526-632X. ; 96:7, s. e1036-e1044
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To establish the significance of glucocerebrosidase gene (GBA) carrier status on motor impairment in a large cohort of patients with incident Parkinson disease (PD). METHODS: Three European population-based studies followed 528 patients with PD from diagnosis. A total of 440 with genomic DNA from baseline were assessed for GBA variants. We evaluated motor and functional impairment annually using the Unified Parkinson's Disease Rating Scale (UPDRS) motor and activities of daily living (ADL) sections. Differential effects of classes of GBA variants on disease progression were evaluated using mixed random and fixed effects models. RESULTS: A total of 387 patients with idiopathic disease (age at baseline 70.3 ± 9.5 years; 60.2% male) and 53 GBA carriers (age at baseline 66.8 ± 10.1 years; 64.2% male) were included. The motor profile of the groups was clinically indistinguishable at diagnosis. GBA carriers showed faster annual increase in UPDRS scores measuring ADL (1.5 point per year, 95% confidence interval [CI] 1.1-2.0) and motor symptoms (2.2 points per year, 95% CI 1.3-3.1) compared to noncarriers (ADL, 1.0 point per year, 95% CI 0.9-1.1, p = 0.003; motor, 1.3 point per year, 95% CI 1.1-1.6, p = 0.007). Simulations of clinical trial designs showed that recruiting only GBA carriers can reduce trial size by up to 65% compared to a trial recruiting all patients with PD. CONCLUSION: GBA variants are linked to a more aggressive motor disease course over 7 years from diagnosis in patients with PD. A better understanding of PD progression in genetic subpopulations may improve disease management and has direct implications for improving the design of clinical trials.
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48.
  • Maple-Grødem, Jodi, et al. (författare)
  • Lack of Association between GBA Mutations and Motor Complications in European and American Parkinson's Disease Cohorts
  • 2021
  • Ingår i: Journal of Parkinson's Disease. - : IOS Press. - 1877-7171 .- 1877-718X. ; 11:4, s. 1569-1578
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Motor complications are a consequence of the chronic dopaminergic treatment of Parkinson's disease (PD) and include levodopa-induced dyskinesia (LIDs) and motor fluctuations (MF). Currently, evidence is on lacking whether patients with GBA-associated PD differ in their risk of developing motor complications compared to the general PD population.Objective: To evaluate the association of GBA carrier status with the development of LIDS and MFs from early PD.Methods: Motor complications were recorded prospectively in 884 patients with PD from four longitudinal cohorts using part IV of the UPDRS or MDS-UPDRS. Subjects were followed for up to 11 years and the associations of GBA mutations with the development of motor complications were assessed using parametric accelerated failure time models.Results: In 439 patients from Europe, GBA mutations were detected in 53 (12.1%) patients and a total of 168 cases of LIDs and 258 cases of MF were observed. GBA carrier status was not associated with the time to develop LIDs (HR 0.78, 95%CI 0.47 to 1.26, p = 0.30) or MF (HR 1.19, 95%CI 0.84 to 1.70, p = 0.33). In the American cohorts, GBA mutations were detected in 36 (8.1%) patients and GBA carrier status was also not associated with the progression to LIDs (HR 1.08, 95%CI 0.55 to 2.14, p = 0.82) or MF (HR 1.22, 95%CI 0.74 to 2.04, p = 0.43).Conclusion: This study does not provide evidence that GBA-carrier status is associated with a higher risk of developing motor complications. Publication of studies with null results is vital to develop an accurate summary of the clinical features that impact patients with GBA-associated PD.
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49.
  • Mendham, Amy, et al. (författare)
  • Osteoporosis in older black South African women and relationships with body composition, dietary intake and physical activity
  • 2020
  • Ingår i: 13th European Nutrition Conference, FENS 2019, 15–18 October 2019, Malnutrition in an Obese World: European Perspectives. - : Cambridge University Press. ; , s. E441-E441
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Osteoporosis was not a public health concern in black South African (SA) women, until recently when it was reported that the prevalence of vertebral fractures was 9.1% in black compared to 5.0% in white SA women. Accordingly, this study aimed to measure bone mineral density (BMD) of older black SA women and to investigate its association with risk factors for osteoporosis, including strength, muscle and fat mass, dietary intake and objectively measured physical activity (PA).Methods and materials: Older black SA women (age, 68 (range; 60–85 years) n = 122) completed sociodemographic and quantitative food frequency questionnaires (QFFQ), fasting venous blood samples (25-hydroxycholecalciferol: Vitamin D-25), 24 h urine collection (estimate protein intake), grip strength and PA monitoring (activPAL). Dual-energy x-ray absorptiometry (DXA) scans of the hip (femoral neck and total) and lumbar spine determined BMD and whole-body scans for fat and fat-free soft tissue mass (FFSTM). WHO classifications were used to determine osteopenia (t-score -2.5 to -1), and osteoporosis (t-score < -2.5).Results: At the lumbar spine 34.4% of the women (n = 42) had osteopenia and 19.7% (n = 24) had osteoporosis. Osteopenia at the left femoral neck was 32% (n = 40) and osteoporosis was 13.1% (n = 16) of participants. The total left hip BMD indicated osteopenia in 27.9% (n = 34) and osteoporosis in 13.1% (n = 16) of participants. Multinomial regression revealed no differences in age (y) or frequency of falls in the past year between all groups (p = 0.727). Compared to those with normal BMD, participants with osteoporosis at the hip neck and lumbar spine were shorter, weighed less and had a lower body mass index (BMI) (all p < 0.05). When adjusted for height, the osteoporotic group (hip neck and lumbar spine) had lower trunk fat (% whole body), FFSTM (kg) and grip strength (kg), compared to those with normal BMD (p < 0.05). Only protein intake (g; 24 h urine analyses) was lower in women with osteoporosis (all sites) compared to those with normal BMD. Fat, carbohydrate and micronutrient intakes (relative to total daily energy intake), and vitamin D concentrations were not associated with BMD (all sites). Number of daily step count and stepping time (min) were inversely associated with BMI (p < 0.05), but not with BMD (all sites; p > 0.05).Discussion: A high prevalence of osteopenia and osteoporosis was evident at the lumbar spine and hip in older black SA women. This study highlights the importance of strength, body composition, and protein intake in maintaining BMD and preventing the development of osteoporosis in older women.
  •  
50.
  • Olsson, Ann-Margreth E., 1952- (författare)
  • Listening to the voice of children : systemic dialogue coaching. Inviting participation and partnership in social work
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This is a study in and about systemic coaching in social work – systemic, and, as it unfolded, dialogical coaching, later named Dialogue Coaching (DC). Focus lies on what the conducted coaching brought forth, generated and created in the context of social work and for the members of the participating social welfare organisations. My specialities as coach became to inspire social workers to invite clients and especially children into partnership, making their voices heard, both in the written text and in the process of social investigations.  The study was integral parts of commissions (and vice versa) of the County Administrative Board of Scania, Sweden, in my profession as systemic consultant and supervisor in Sweden. It was a study in how dialogical communication could improve how social workers, listening to the children’s invitation, could make children’s voices more heard in social investigations. In all, 55 social workers in seven municipalities participated in the dialogical participatory action research (DPAR) study, developing coaching and improving the dialogical interaction in social investigations. Focus moved from collecting data for decision-making, about what would be best for the child and other clients,tofocusing on the changing process in relation to the participating clients, including children when they wanted to and could, co-creating new orientation on how to go on.  The focus on communication and dialogue in the coaching changed and developed the participants’ approach in relation to clients and one another and others.  In the emerging awareness of how we reciprocally and reflexively co-create occurrences and outcomes, including who we become in relation to one another, the participating social workers’ awareness of the impact of their own contributions, and their own importance in relation to children and other clients, also improved. The expressions listening ears and listening questions were invented, capturing my, the coach’s, participation of placing myself completely at the other participants’ disposal, completely accessible in the mutual responsiveness in the moment – being here and now in the present. The systemic methods and techniques were reflexively influenced and adapted from within the relational dynamic of joint actions in the dialogical interplay, metaphorically presented as peloton cycling in a voyage tour, becoming living tools in both the social workers’ practice and the coaching researcher’s practice, facilitating learning-by-doing with methods and approach connected to Appreciative Inquiry (AI).  One of the living tools was reflecting teams emerging also into so called delta-reflecting teams­ with open narrating included.
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