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1.
  • Mishra, A, et al. (author)
  • Diminishing benefits of urban living for children and adolescents' growth and development
  • 2023
  • In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
  • Journal article (peer-reviewed)abstract
    • Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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  • Abe, O, et al. (author)
  • Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
  • 2005
  • In: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
  • Journal article (peer-reviewed)abstract
    • Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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  • Niedermaier, O., et al. (author)
  • "Safe" Coulomb excitation of Mg-30
  • 2005
  • In: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 94:17, s. 172501 (artno)-
  • Journal article (peer-reviewed)abstract
    • We report on the first radioactive beam experiment performed at the recently commissioned REX-ISOLDE facility at CERN in conjunction with the highly efficient γ spectrometer MINIBALL. Using Mg-30 ions accelerated to an energy of 2.25 MeV/u together with a thin Ni-nat target, Coulomb excitation of the first excited 2(+) states of the projectile and target nuclei well below the Coulomb barrier was observed. From the measured relative deexcitation γ-ray yields the B(E2;0(gs)(+)&RARR; 2(1)(+)) value of Mg-30 was determined to be 241(31)e(2) fm(4). Our result is lower than values obtained at projectile fragmentation facilities using the intermediate-energy Coulomb excitation method, and confirms the theoretical conjecture that the neutron-rich magnesium isotope Mg-30 resides outside the "island of inversion."
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  • Niedermaier, O., et al. (author)
  • The neutron-rich Mg isotopes: first results from MINIBALL at REX-ISOLDE
  • 2005
  • In: Nuclear Physics A. - : Elsevier BV. - 0375-9474. ; 752, s. 273-273
  • Journal article (peer-reviewed)abstract
    • We report on the first radioactive beam experiment performed at the recently commissioned REX-ISOLDE facility at CERN in conjunction with the highly efficient γ spectrometer MINIBALL. Using Mg-30 ions accelerated to an energy of 2.25 MeV/u together with a thin Ni-nat target, Coulomb excitation of the first excited 2(+) states of the projectile and target nuclei well below the Coulomb barrier was observed. From the measured relative deexcitation γ-ray yields the B(E2;0(gs)(+)&RARR; 2(1)(+)) value of Mg-30 was determined to be 241(31)e(2) fm(4). Our result is lower than values obtained at projectile fragmentation facilities using the intermediate-energy Coulomb excitation method, and confirms the theoretical conjecture that the neutron-rich magnesium isotope Mg-30 resides outside the "island of inversion."
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  • Scheit, H., et al. (author)
  • Coulomb excitation of neutron-rich beams at REX-ISOLDE
  • 2005
  • In: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-601X .- 1434-6001. ; 25:Suppl. 1, s. 397-402
  • Conference paper (peer-reviewed)abstract
    • After the successful commissioning of the radioactive beam experiment at ISOLDE (REX-ISOLDE) - an accelerator for exotic nuclei produced by ISOLDE - in 2002 and the promotion to a CERN user facility in 2003, first physics experiments using these beams were performed. Initial experiments focused on the region of deformation in the vicinity of the neutron-rich Na and Mg isotopes. Preliminary results on the neutron-rich Na and Mg isotopes show the high potential and physics opportunities offered by the exotic isotope accelerator REX in conjunction with the modern Germanium gamma spectrometer MINIBALL.
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  • van der Lee, S. J., et al. (author)
  • A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity
  • 2019
  • In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 138:2, s. 237-250
  • Journal article (peer-reviewed)abstract
    • The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLC gamma 2 pathway as drug-target.
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10.
  • Habs, D., et al. (author)
  • The REX-ISOLDE project
  • 2000
  • In: Hyperfine Interactions. - 0304-3843 .- 1572-9540. ; 129:1-4, s. 43-66
  • Journal article (peer-reviewed)abstract
    • The Radioactive Beam Experiment REX-ISOLDE [1-3] is a pilot experiment at ISOLDE (CERN) testing the new concept of post acceleration of radioactive ion beams by using charge breeding of the ions in a high charge state ion source and the efficient acceleration of the highly charged ions in a short LINAC using modern ion accelerator structures. In order to prepare the ions for the experiments singly charged radioactive ions from the on-line mass separator ISOLDE will be cooled and bunched in a Penning trap, charge bred in an electron beam ion source (EBIS) and finally accelerated in the LINAC. The LINAC consists of a radiofrequency quadrupole (RFQ) accelerator, which accelerates the ions up to 0.3 MeV/u, an interdigital H-type (IH) structure with a final energy between 1.1 and 1.2 MeV/u and three seven gap resonators, which allow the variation of the final energy. With an energy of the radioactive beams between 0.8 MeV/u and 2.2 MeV/u a wide range of experiments in the field of nuclear spectroscopy, astrophysics and solid state physics will be addressed by REX-ISOLDE.
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  • Kester, O., et al. (author)
  • Accelerated radioactive beams from REX-ISOLDE
  • 2003
  • In: Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms. - 0168-583X. ; 204, s. 20-20
  • Conference paper (peer-reviewed)abstract
    • In 2001 the linear accelerator of the Radioactive beam EXperiment (REX-ISOLDE) delivered for the first time accelerated radioactive ion beams, at a beam energy of 2 MeV/u. REX-ISOLDE uses the method of charge-state breeding, in order to enhance the charge state of the ions before injection into the LINAC. Radioactive singly-charged ions from the on-line mass separator ISOLDE are first accumulated in a Penning trap, then charge bred to an A/q
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  • Marra, Giancarlo, et al. (author)
  • Impact of Epithelial Histological Types, Subtypes, and Growth Patterns on Oncological Outcomes for Patients with Nonmetastatic Prostate Cancer Treated with Curative Intent: A Systematic Review.
  • 2023
  • In: European urology. - 0302-2838 .- 1873-7560. ; 84:1, s. 65-85
  • Journal article (peer-reviewed)abstract
    • The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for conventional PCa and so different approaches may be needed.To compare oncological outcomes for conventional and UH PCa in men with localized disease treated with curative intent.A systematic review adhering to the Referred Reporting Items for Systematic Reviews and Meta-Analyses was prospectively registered on PROSPERO (CRD42022296013) was performed in July 2021.We screened 3651 manuscripts and identified 46 eligible studies (reporting on 1871814 men with conventional PCa and 6929 men with 10 different PCa UHs). Extraprostatic extension and lymph node metastases, but not positive margin rates, were more common with UH PCa than with conventional tumors. PCa cases with cribriform pattern, intraductal carcinoma, or ductal adenocarcinoma had higher rates of biochemical recurrence and metastases after radical prostatectomy than for conventional PCa cases. Lower cancer-specific survival rates were observed for mixed cribriform/intraductal and cribriform PCa. By contrast, pathological findings and oncological outcomes for mucinous and prostatic intraepithelial neoplasia (PIN)-like PCa were similar to those for conventional PCa. Limitations of this review include low-quality studies, a risk of reporting bias, and a scarcity of studies that included radiotherapy.Intraductal, cribriform, and ductal UHs may have worse oncological outcomes than for conventional and mucinous or PIN-like PCa. Alternative treatment approaches need to be evaluated in men with these cancers.We reviewed the literature to explore whether prostate cancers with unconventional growth patterns behave differently to conventional prostate cancers. We found that some unconventional growth patterns have worse outcomes, so we need to investigate if they need different treatments. Urologists should be aware of these growth patterns and their clinical impact.
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  • Huijben, Jilske A., et al. (author)
  • Development of a quality indicator set to measure and improve quality of ICU care for patients with traumatic brain injury
  • 2019
  • In: Critical Care. - : BioMed Central. - 1364-8535 .- 1466-609X. ; 23
  • Journal article (peer-reviewed)abstract
    • Background: We aimed to develop a set of quality indicators for patients with traumatic brain injury (TBI) in intensive care units (ICUs) across Europe and to explore barriers and facilitators for implementation of these quality indicators.Methods: A preliminary list of 66 quality indicators was developed, based on current guidelines, existing practice variation, and clinical expertise in TBI management at the ICU. Eight TBI experts of the Advisory Committee preselected the quality indicators during a first Delphi round. A larger Europe-wide expert panel was recruited for the next two Delphi rounds. Quality indicator definitions were evaluated on four criteria: validity (better performance on the indicator reflects better processes of care and leads to better patient outcome), feasibility (data are available or easy to obtain), discriminability (variability in clinical practice), and actionability (professionals can act based on the indicator). Experts scored indicators on a 5-point Likert scale delivered by an electronic survey tool.Results. The expert panel consisted of 50 experts from 18 countries across Europe, mostly intensivists (N=24, 48%) and neurosurgeons (N=7, 14%). Experts agreed on a final set of 42 indicators to assess quality of ICU care: 17 structure indicators, 16 process indicators, and 9 outcome indicators. Experts are motivated to implement this finally proposed set (N=49, 98%) and indicated routine measurement in registries (N=41, 82%), benchmarking (N=42, 84%), and quality improvement programs (N=41, 82%) as future steps. Administrative burden was indicated as the most important barrier for implementation of the indicator set (N=48, 98%).Conclusions: This Delphi consensus study gives insight in which quality indicators have the potential to improve quality of TBI care at European ICUs. The proposed quality indicator set is recommended to be used across Europe for registry purposes to gain insight in current ICU practices and outcomes of patients with TBI. This indicator set may become an important tool to support benchmarking and quality improvement programs for patients with TBI in the future.
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  • Jeppesen, H. B., et al. (author)
  • Investigation of the Li-9+H-2 -> Li-8+t reaction at REX-ISOLDE
  • 2006
  • In: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 635, s. 17-17
  • Journal article (peer-reviewed)abstract
    • The one-neutron transfer reaction Li-9 + H-2 -> Li-8 + t has been investigated in an inverse kinematics experiment by bombarding a deuterated polypropylene target with a 2.36 MeV/u Li-9 beam from the post-accelerator REX-ISOLDE at CERN. Excitation energies in Li-8 as well as angular distributions of the tritons were obtained and spectroscopic factors deduced. (c) 2006 Elsevier B.V. All rights reserved.
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  • Jeppesen, H. B., et al. (author)
  • Low energy reactions with radioactive ions at REX-ISOLDE - the Li-9+H-2 case
  • 2005
  • In: Nuclear Physics A. - : Elsevier BV. - 0375-9474. ; 748, s. 374-374
  • Journal article (peer-reviewed)abstract
    • At the newly constructed postaccelerator REX-ISOLDE (Radioactive beam Experiment at ISOLDE) we have investigated reactions induced by a Li-9 beam incident on a deuterium target at an energy of 2.36 MeV/u. Most reaction channels were recorded. From one-neutron transfer the differential cross-section for the low lying Li-10 spectrum is found. The results from the other channels demonstrate the great applicability and many possibilities that REX-ISOLDE opens up.
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  • Modi, A., et al. (author)
  • Association of gastrointestinal events with quality of life and treatment satisfaction in osteoporosis patients: results from the Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC OS)
  • 2017
  • In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 28:10, s. 2867-2876
  • Journal article (peer-reviewed)abstract
    • The purpose of this study was to assess the association of GI events with HRQoL and treatment satisfaction. The effect of baseline GI events persisted through 1 year of follow-up, as indicated by lower EQ-5D, OPAQ-SV, and treatment satisfaction scores among patients with vs without baseline GI events. The presence of GI events is an independent predictor of decreased HRQoL and treatment satisfaction in patients being treated for osteoporosis. Introduction The goal of this study was to assess the association of gastrointestinal (GI) events with health-related quality of life (HRQoL) and treatment satisfaction in patients being treated for osteoporosis. Methods MUSIC OS was a multinational, prospective, observational study examining the impact of GI events on osteoporosis management in postmenopausal women. In this analysis, HRQoL and treatment satisfaction were assessed at baseline, 6, and 12 months and compared between patients with and without GI events. Covariate-adjusted scores were calculated using multivariate least-squares regression analysis, and differences between the mean scores of patients with and without baseline and post-baseline GI events were determined. Results Among the 2959 patients in the analysis, unadjusted scores at each time point were lower (i.e., worse) for patients with GI events than patients without GI events. In adjusted analyses, the effect of baseline GI events persisted through 1 year of follow-up, as indicated by lower EQ-5D and OPAQ-SV scores at 12 months among patients with vs without baseline GI events (-0.04 for the EQ-5D utility score, -5.07 for the EQ-5D visual analog scale, -3.35 for OPAQ physical function, -4.60 for OPAQ emotional status, and -8.50 for OPAQ back pain; P <= 0.001 for all values). Decrements in month 12 treatment satisfaction scores were -6.46 for patients with baseline GI events and -7.88 for patients with post-baseline GI events. Conclusions The presence of GI events is an independent predictor of decreased HRQoL and treatment satisfaction in patients being treated for osteoporosis.
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  • Modi, A., et al. (author)
  • Rationale and design of MUSIC OS-EU: an international observational study of the treatment of postmenopausal women for Osteoporosis in Europe and Canada
  • 2015
  • In: Clinical and Experimental Rheumatology. - 0392-856X. ; 33:4, s. 537-544
  • Journal article (peer-reviewed)abstract
    • Objective The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC OS-EU) was designed to better understand the rate and burden of gastrointestinal (GI) events on clinical and health care outcomes among postmenopausal women with osteoporosis. MUSIC OS-EU is a prospective, multinational, observational cohort study of postmenopausal women >= 50 years of age diagnosed with osteoporosis and enrolled in physician clinics in six countries: France, Italy, the Netherlands, Sweden, the United Kingdom, and Canada. The MUSIC OS-EU study has three components: (i) a physician survey to describe their management of osteoporotic patients with GI events; (ii) a retrospective chart survey to describe the receipt and type of osteoporosis medication prescribed; and (iii) a prospective cohort study including untreated and treated patients diagnosed with osteoporosis to investigate the rate of GI events and association with osteoporosis medication use patterns, health-related quality of life, treatment satisfaction and resource utilisation among postmenopausal women with osteoporosis. Physicians at 97 sites completed the physician questionnaire and data for 716 patients were abstracted for the retrospective chart review. Enrolment and the baseline data collection for the prospective cohort study were conducted between March 2012 and June 2013 for 292 untreated and 2,959 treated patients, of whom 684 were new users and 2,275 were experienced users of oral osteoporosis medications. The results of MUSIC OS-EU will illuminate the association of GI events with the management of osteoporosis and with patient-reported outcomes among postmenopausal women with osteoporosis in Europe and Canada.
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  • Modi, A., et al. (author)
  • The impact of GI events on persistence and adherence to osteoporosis treatment: 3-, 6-, and 12-month findings in the MUSIC-OS study
  • 2018
  • In: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 29:2, s. 329-337
  • Journal article (peer-reviewed)abstract
    • The goal of this multinational, prospective, observational study was to examine the relationship between gastrointestinal (GI) events and self-reported levels of medication adherence and persistence in postmenopausal women. A total of 73.9% of patients remained on their osteoporosis (OP) therapy at month 12, although the presence of a GI event at baseline, month 3, and month 6 significantly reduced month 12 persistence among new users. The odds of a month-12 ADEOS score >= 20 were significantly lower among patients who experienced a GI event between baseline and month 6. The occurrence of GI events was observed to be associated with a lower likelihood of patient adherence and persistence to OP medication. This study examines the relationship between gastrointestinal (GI) events and self-reported adherence and persistence with initial osteoporosis (OP) therapy over the course of the first 12 months of treatment. The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study was a multinational, prospective, observational study examining the impact of GI events on OP management in postmenopausal women. Information regarding GI events was collected at the time of enrollment and at months 3, 6, and 12 of follow-up. Patients reported GI events and medication persistence and completed the 12-item Adherence Evaluation of Osteoporosis treatment (ADEOS) questionnaire. Multivariate logistic and general linear models examined the association between GI events at various time points and persistence and adherence at month 12. The study enrolled 2943 women; 22.8% were classified as new users of OP therapy and the remainder were considered experienced users. Across all patients, 68.1% reported GI events at baseline; by month 12, over 80% of subjects who completed follow-up reported at least one GI problem. The majority of patients (86.7%) were treated only with bisphosphonates at baseline. At month 12, 73.9% of patients remained on therapy; logistic regression revealed that those with GI problems by month 6 were significantly less likely to persist with treatment, after adjusting for other factors. The odds of a month 12 ADEOS score >= 20 (considered predictive of adherence) were significantly lower among patients who experienced a GI event between baseline and month 6. The occurrence of GI events was associated with a lower likelihood of patient adherence to and persistence with OP medication.
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  • Pauwels, D., et al. (author)
  • Gamow-Teller decay population of Ni-64 levels in the decay of 1(+) Co-64
  • 2012
  • In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 86:6, s. 064318-
  • Journal article (peer-reviewed)abstract
    • The Co-64 beta-decay feeding levels in the well-studied Ni-64 nucleus were investigated. Whereas the previously known Co-64 decay scheme merely contained 2 gamma rays, the decay scheme established in this work contains 18, of which 5 are observed in this work and 6 were previously observed in an (n, gamma) study but not placed in the Ni-64 level scheme. Surprisingly, one additional level-placed at an excitation energy of 3578.7 keV-could be determined. The observed beta-decay paths involve allowed nu f(5/2) -> pi f(7/2) and nu p(1/2) -> pi p(3/2) transitions. Three strongly fed levels around 4 MeV are interpreted to possess possible proton-intruder character.
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  • Radulov, D., et al. (author)
  • beta decay of Mn-61 to levels in Fe-61
  • 2013
  • In: Physical Review C. Nuclear Physics. - : American Physical Society. - 0556-2813 .- 1089-490X. ; 88:1, s. 014307-
  • Journal article (peer-reviewed)abstract
    • A detailed beta-decay study of Mn-61 is presented, yielding extended information on the level structure of Fe-61. Pure beams were obtained at ISOLDE, CERN, after selective laser ionization and mass separation of fission products from the bombardment of a UCx target by 1.4-GeV protons. The beta and gamma information was detected by two MiniBall clusters and three Delta E plastic scintillators. The new Mn-61 decay scheme reveals 48 gamma transitions, distributed over 20 excited states. A comparison to the decay scheme of Mn-59 and excited states in Fe-59 is made. Shell-model calculations with two different interactions are performed in order to compare the nuclear structure of the two neighboring odd-A iron isotopes. Tentative spin and parities of several excited states in Fe-61 are assigned on the basis of beta-decay feeding patterns in both Fe-59,Fe-61 and of results from the theoretical shell-model calculations.
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  • Carrington, G., et al. (author)
  • Human skeletal myopathy myosin mutations disrupt myosin head sequestration
  • 2023
  • In: JCI Insight. - 2379-3708. ; 8:21
  • Journal article (peer-reviewed)abstract
    • Myosin heavy chains encoded by MYH7 and MYH2 are abundant in human skeletal muscle and important for muscle contraction. However, it is unclear how mutations in these genes disrupt myosin structure and function leading to skeletal muscle myopathies termed myosinopathies. Here, we used multiple approaches to analyze the effects of common MYH7 and MYH2 mutations in the light meromyosin (LMM) region of myosin. Analyses of expressed and purified MYH7 and MYH2 LMM mutant proteins combined with in silico modeling showed that myosin coiled coil structure and packing of filaments in vitro are commonly disrupted. Using muscle biopsies from patients and fluorescent ATP analog chase protocols to estimate the proportion of myosin heads that were super-relaxed, together with x-ray diffraction measurements to estimate myosin head order, we found that basal myosin ATP consumption was increased and the myosin super-relaxed state was decreased in vivo. In addition, myofiber mechanics experiments to investigate contractile function showed that myofiber contractility was not affected. These findings indicate that the structural remodeling associated with LMM mutations induces a pathogenic state in which formation of shutdown heads is impaired, thus increasing myosin head ATP demand in the filaments, rather than affecting contractility. These key findings will help design future therapies for myosinopathies.
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  • Malfatti, Edoardo, et al. (author)
  • A New Muscle Glycogen Storage Disease Associated with Glycogenin-1 Deficiency
  • 2014
  • In: Annals of Neurology. - : Wiley. - 0364-5134. ; 76:6, s. 891-898
  • Journal article (peer-reviewed)abstract
    • We describe a slowly progressive myopathy in 7 unrelated adult patients with storage of polyglucosan in muscle fibers. Genetic investigation revealed homozygous or compound heterozygous deleterious variants in the glycogenin-1 gene (GYG1). Most patients showed depletion of glycogenin-1 in skeletal muscle, whereas 1 showed presence of glycogenin-1 lacking the C-terminal that normally binds glycogen synthase. Our results indicate that either depletion of glycogenin-1 or impaired interaction with glycogen synthase underlies this new form of glycogen storage disease that differs from a previously reported patient with GYG1 mutations who showed profound glycogen depletion in skeletal muscle and accumulation of glycogenin-1. Ann Neurol 2014;76:891-898
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