| 1. |
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| 2. |
- Maier, Hannes, et al.
(författare)
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Consensus Statement on Bone Conduction Devices and Active Middle Ear Implants in Conductive and Mixed Hearing Loss
- 2022
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Ingår i: Otology and Neurotology. - : Lippincott, Williams & Wilkins. - 1531-7129 .- 1537-4505. ; 43:5, s. 513-529
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Tidskriftsartikel (refereegranskat)abstract
- Nowadays, several options are available to treat patients with conductive or mixed hearing loss. Whenever surgical intervention is not possible or contra-indicated, and amplification by a conventional hearing device (e.g., behind-the-ear device) is not feasible, then implantable hearing devices are an indispensable next option. Implantable bone-conduction devices and middle-ear implants have advantages but also limitations concerning complexity/invasiveness of the surgery, medical complications, and effectiveness. To counsel the patient, the clinician should have a good overview of the options with regard to safety and reliability as well as unequivocal technical performance data. The present consensus document is the outcome of an extensive iterative process including ENT specialists, audiologists, health-policy scientists, and representatives/technicians of the main companies in this field. This document should provide a first framework for procedures and technical characterization to enhance effective communication between these stakeholders, improving health care.
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| 3. |
- Curtis, Bruce A., et al.
(författare)
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Algal genomes reveal evolutionary mosaicism and the fate of nucleomorphs
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7427, s. 59-65
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Tidskriftsartikel (refereegranskat)abstract
- Cryptophyte and chlorarachniophyte algae are transitional forms in the widespread secondary endosymbiotic acquisition of photosynthesis by engulfment of eukaryotic algae. Unlike most secondary plastid-bearing algae, miniaturized versions of the endosymbiont nuclei (nucleomorphs) persist in cryptophytes and chlorarachniophytes. To determine why, and to address other fundamental questions about eukaryote-eukaryote endosymbiosis, we sequenced the nuclear genomes of the cryptophyte Guillardia theta and the chlorarachniophyte Bigelowiella natans. Both genomes have >21,000 protein genes and are intron rich, and B. natans exhibits unprecedented alternative splicing for a single-celled organism. Phylogenomic analyses and subcellular targeting predictions reveal extensive genetic and biochemical mosaicism, with both host-and endosymbiont-derived genes servicing the mitochondrion, the host cell cytosol, the plastid and the remnant endosymbiont cytosol of both algae. Mitochondrion-to-nucleus gene transfer still occurs in both organisms but plastid-to-nucleus and nucleomorph-to-nucleus transfers do not, which explains why a small residue of essential genes remains locked in each nucleomorph.
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| 4. |
- Ghoncheh, Mohammad, et al.
(författare)
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Output performance of the novel active transcutaneous bone conduction implant Sentio at different stimulation sites
- 2022
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Ingår i: Hearing Research. - : ELSEVIER. - 0378-5955 .- 1878-5891. ; 421
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The output performance of a novel semi-implantable transcutaneous bone conduction device was compared to an established percutaneous bone-anchored hearing system device using cadaver heads. The influence of actuator position, tissue growth below the actuator and mounting it on the surface or in a flattened bone bed on the performance of the implanted actuator was investigated.Materials and Methods: The percutaneous and the new transcutaneous device were sequentially implanted at two sites in five human cadaver heads: 55 mm superior-posterior to the ear canal opening (position A) and, closer to the cochlea, about 20 mm inferior-posterior to the ear canal opening behind the pinna on the mastoid (position B). The ipsi-and contralateral cochlear promontory (CP) velocity magnitude responses to percutaneous and transcutaneous stimulation were measured using laser Doppler vibrometry. In addition, the CP vibration of the transcutaneous device placed directly on the skull bone surface was compared with the placement in a flattened bone bed at a depth of about 3 mm. Finally, the influence of placing a thin silicone interposition layer under the implanted transducer was also explored.Results: The percutaneous device provided about an 11 dB higher average CP vibration level than the transcutaneous device at frequencies between 0.5 and 10 kHz. The ipsilateral CP vibration responses with stimulations at position B were on average 13 dB higher compared to stimulation at position A. The placement of the transcutaneous transducer at position B provided similar or higher average vibration magnitudes than the percutaneous transducer at position A. The 3 mm deep flattened bone bed had no significant effects on the output performance. Placing a thin silicone layer under the transcutaneous transducer had no significant influence on the output of the transcutaneous device.Conclusions: Our results using the CP vibration responses show that at frequencies above 500 Hz the new transcutaneous device at position B provides similar output levels as the percutaneous device at position A. The results also indicated that neither a bone bed for the placement of the transcutaneous transducer nor a simulated tissue growth between the actuator and the bone affect the output performance of the device.
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| 5. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
- 2015
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
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| 6. |
- Kleineidam, Luca, et al.
(författare)
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Midlife occupational cognitive requirements protect cognitive function in old age by increasing cognitive reserve
- 2022
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Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Several lifestyle factors promote protection against Alzheimer's disease (AD) throughout a person's lifespan. Although such protective effects have been described for occupational cognitive requirements (OCR) in midlife, it is currently unknown whether they are conveyed by brain maintenance (BM), brain reserve (BR), or cognitive reserve (CR) or a combination of them. Methods: We systematically derived hypotheses for these resilience concepts and tested them in the population-based AgeCoDe cohort and memory clinic-based AD high-risk DELCODE study. The OCR score (OCRS) was measured using job activities based on the O*NET occupational classification system. Four sets of analyses were conducted: (1) the interaction of OCR and APOE-ε4 with regard to cognitive decline (N = 2,369, AgeCoDe), (2) association with differentially shaped retrospective trajectories before the onset of dementia of the Alzheimer's type (DAT; N = 474, AgeCoDe), (3) cross-sectional interaction of the OCR and cerebrospinal fluid (CSF) AD biomarkers and brain structural measures regarding memory function (N = 873, DELCODE), and (4) cross-sectional and longitudinal association of OCR with CSF AD biomarkers and brain structural measures (N = 873, DELCODE). Results: Regarding (1), higher OCRS was associated with a reduced association of APOE-ε4 with cognitive decline (mean follow-up = 6.03 years), consistent with CR and BR. Regarding (2), high OCRS was associated with a later onset but subsequently stronger cognitive decline in individuals converting to DAT, consistent with CR. Regarding (3), higher OCRS was associated with a weaker association of the CSF Aβ42/40 ratio and hippocampal volume with memory function, consistent with CR. Regarding (4), OCR was not associated with the levels or changes in CSF AD biomarkers (mean follow-up = 2.61 years). We found a cross-sectional, age-independent association of OCRS with some MRI markers, but no association with 1-year-change. OCR was not associated with the intracranial volume. These results are not completely consistent with those of BR or BM. Discussion: Our results support the link between OCR and CR. Promoting and seeking complex and stimulating work conditions in midlife could therefore contribute to increased resistance to pathologies in old age and might complement prevention measures aimed at reducing pathology.
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| 7. |
- Adlarson, Patrik, et al.
(författare)
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Exclusive measurement of the eta -> pi(+) pi(-) gamma decay
- 2012
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 707:2, s. 243-249
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Tidskriftsartikel (refereegranskat)abstract
- An exclusive measurement of the decay eta -> pi(+) pi(-) gamma has been performed at the WASA facility at COSY. The eta mesons were produced in the fusion reaction pd -> He-3 X at a proton beam momentum of 1.7 GeV/c. Efficiency corrected differential distributions have been extracted based on 13 960 +/- 140 events after background subtraction. The measured pion angular distribution is consistent with a relative p-wave of the two-pion system, whereas the measured photon energy spectrum was found at variance with the simplest gauge invariant matrix element of eta -> pi(+) pi(-) gamma. A parameterization of the data can be achieved by the additional inclusion of the empirical pion vector form factor multiplied by a first-order polynomial in the squared invariant mass of the pi(+) pi(-) system.
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| 8. |
- Adlarson, Patrik, et al.
(författare)
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Measurement of the ω → π+π−π0 Dalitz plot distribution : The WASA-at-COSY Collaboration
- 2017
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 770, s. 418-425
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Tidskriftsartikel (refereegranskat)abstract
- Using the production reactions pd -> He-3 omega and pp -> pp omega, the Dalitz plot distribution for the omega -> pi(+)pi(-)pi(0)decay is studied with the WASA detector at COSY, based on a combined data sample of (4.408 +/- 0.042) x 10(4) events. The Dalitz plot density is parametrised by a product of the P-wave phase space and a polynomial expansion in the normalised polar Dalitz plot variables Z and phi. For the first time, a deviation from pure P-wave phase space is observed with a significance of 4.1 sigma. The deviation is parametrised by a linear term 1+2 alpha Z, with alpha determined to be +0.147 +/- 0.036, consistent with the expectations of rho-meson-type final-state interactions of the P-wave pion pairs. (C) 2017 The Author. Published by Elsevier B.V.
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| 9. |
- Andersen, Jeppe R., et al.
(författare)
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A Positive Resampler for Monte Carlo events with negative weights
- 2020
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:11
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Tidskriftsartikel (refereegranskat)abstract
- We propose the Positive Resampler to solve the problem associated with event samples from state-of-the-art predictions for scattering processes at hadron colliders typically involving a sizeable number of events contributing with negative weight. The proposed method guarantees positive weights for all physical distributions, and a correct description of all observables. A desirable side product of the method is the possibility to reduce the size of event samples produced by General Purpose Event Generators, thus lowering the resource demands for subsequent computing-intensive event processing steps. We demonstrate the viability and efficiency of our approach by considering its application to a next-to-leading order + parton shower merged prediction for the production of a W boson in association with multiple jets.
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| 10. |
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| 11. |
- DeAngelis, Nicola, et al.
(författare)
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2020 WSES guidelines for the detection and management of bile duct injury during cholecystectomy
- 2021
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Ingår i: World Journal of Emergency Surgery. - : BMC. - 1749-7922. ; 16:1
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Forskningsöversikt (refereegranskat)abstract
- Bile duct injury (BDI) is a dangerous complication of cholecystectomy, with significant postoperative sequelae for the patient in terms of morbidity, mortality, and long-term quality of life. BDIs have an estimated incidence of 0.4-1.5%, but considering the number of cholecystectomies performed worldwide, mostly by laparoscopy, surgeons must be prepared to manage this surgical challenge. Most BDIs are recognized either during the procedure or in the immediate postoperative period. However, some BDIs may be discovered later during the postoperative period, and this may translate to delayed or inappropriate treatments. Providing a specific diagnosis and a precise description of the BDI will expedite the decision-making process and increase the chance of treatment success. Subsequently, the choice and timing of the appropriate reconstructive strategy have a critical role in long-term prognosis. Currently, a wide spectrum of multidisciplinary interventions with different degrees of invasiveness is indicated for BDI management. These World Society of Emergency Surgery (WSES) guidelines have been produced following an exhaustive review of the current literature and an international expert panel discussion with the aim of providing evidence-based recommendations to facilitate and standardize the detection and management of BDIs during cholecystectomy. In particular, the 2020 WSES guidelines cover the following key aspects: (1) strategies to minimize the risk of BDI during cholecystectomy; (2) BDI rates in general surgery units and review of surgical practice; (3) how to classify, stage, and report BDI once detected; (4) how to manage an intraoperatively detected BDI; (5) indications for antibiotic treatment; (6) indications for clinical, biochemical, and imaging investigations for suspected BDI; and (7) how to manage a postoperatively detected BDI.
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| 12. |
- Dickmann, Jannis, et al.
(författare)
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A Count Rate-Dependent Method for Spectral Distortion Correction in Photon Counting CT
- 2018
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Ingår i: Medical Imaging 2018. - : SPIE - International Society for Optical Engineering. - 9781510616363
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Konferensbidrag (refereegranskat)abstract
- Rawdata-based material decomposition in spectral CT using photon-counting energy-selective detectors relies on a precise forward model that predicts a count-rate given intersection lengths for each material. This requires extensive system-specific measurements or calibration techniques. Existing calibrations either estimate a detected spectrum and are able to account for spectrally distorted assumptions or correct the predicted count rate using a correction function and can accommodate for count rate-dependent effects such as pulse pileup. We propose a calibration method that uses transmission measurements to optimize a correction function that, unlike existing methods, depends both on the photon energy and the count rate. It is thus able to correct for both kinds of distortions. In a simulated material decomposition into water and iodine, the error was reduced by 96% compared to the best performing reference method if only pulse pileup was present and reduced by 23% if additionally spectral distortions were taken into account. In phantom measurements using a Dectris SANTIS prototype detector, the proposed method allowed to reduce the error by 29% compared to the best performing reference method. Artifacts were below the noise level for the proposed method, while the reference methods either showed an offset in the water region or ring artifacts.
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| 13. |
- Hou, Liping, et al.
(författare)
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Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p=5.87×10(-9); odds ratio=1.12) and markers within ERBB2 (rs2517959, p=4.53×10(-9); odds ratio=1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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| 14. |
- Jansen, Iris E, et al.
(författare)
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Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.
- 2022
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Ingår i: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 144:5, s. 821-842
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n=8074; replication n=5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
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| 15. |
- Jansen, Willemijn J, et al.
(författare)
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Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P=.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P<.001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P<.001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
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| 16. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Tidskriftsartikel (refereegranskat)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 17. |
- Joffrin, E., et al.
(författare)
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Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Forskningsöversikt (refereegranskat)abstract
- For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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| 18. |
- Kuczera, Stefan, et al.
(författare)
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Optimized bias and signal inference in diffusion-weighted image analysis (OBSIDIAN)
- 2021
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 86:5, s. 2716-2732
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Correction of Rician signal bias in magnitude MR images. Methods A model-based, iterative fitting procedure is used to simultaneously estimate true signal and underlying Gaussian noise with standard deviation sigma g on a pixel-by-pixel basis in magnitude MR images. A precomputed function that relates absolute residuals between measured signals and model fit to sigma g is used to iteratively estimate sigma g. The feasibility of the method is evaluated and compared to maximum likelihood estimation (MLE) for diffusion signal decay simulations and diffusion-weighted images of the prostate considering 21 linearly spaced b-values from 0 to 3000 s/mm(2). A multidirectional analysis was performed with publically available brain data. Results Model simulations show that the Rician bias correction algorithm is fast, with an accuracy and precision that is on par to model-based MLE and direct fitting in the case of pure Gaussian noise. Increased accuracy in parameter prediction in a low signal-to-noise ratio (SNR) scenario is ideally achieved by using a composite of multiple signal decays from neighboring voxels as input for the algorithm. For patient data, good agreement with high SNR reference data of diffusion in prostate is achieved. Conclusions OBSIDIAN is a novel, alternative, simple to implement approach for rapid Rician bias correction applicable in any case where differences between true signal decay and underlying model function can be considered negligible in comparison to noise. The proposed composite fitting approach permits accurate parameter estimation even in typical clinical scenarios with low SNR, which significantly simplifies comparison of complex diffusion parameters among studies.
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| 19. |
- Kuczera, Stefan, et al.
(författare)
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Truly reproducible uniform estimation of the ADC with multi-b diffusion data- Application in prostate diffusion imaging
- 2023
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 89:4, s. 1586-1600
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The ADC is a well-established parameter for clinical diagnostic applications, but lacks reproducibility because it is also influenced by the choice diffusion weighting level. A framework is evaluated that is based on multi-b measurement over a wider range of diffusion-weighting levels and higher order tissue diffusion modeling with retrospective, fully reproducible ADC calculation. Methods: Averaging effect from curve fitting for various model functions at 20 linearly spaced b-values was determined by means of simulations and theoretical calculations. Simulation and patient multi-b image data were used to compare the new approach for diffusion-weighted image and ADC map reconstruction with and without Rician bias correction to an active clinical trial protocol probing three non-zero b-values. Results: Averaging effect at a certain b-value varies for model function and maximum b-value used. Images and ADC maps from the novel procedure are on-par with the clinical protocol. Higher order modeling and Rician bias correction is feasible, but comes at the cost of longer computation times. Conclusions: Application of the new framework makes higher order modeling more feasible in a clinical setting while still providing patient images and reproducible ADC maps of adequate quality.
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| 20. |
- Maier, Stephan E, 1959, et al.
(författare)
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Prostate Cancer Diffusion-Weighted Magnetic Resonance Imaging: Does the Choice of Diffusion-Weighting Level Matter?
- 2022
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Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley. - 1053-1807 .- 1522-2586. ; 55:3, s. 842-853
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Tidskriftsartikel (refereegranskat)abstract
- Background Diffusion-weighted magnetic resonance imaging plays an important role in multiparametric assessment of prostate lesions. The derived apparent diffusion coefficient (ADC) could be a useful quantitative biomarker for malignant growth, but lacks acceptance because of low reproducibility. Purpose To investigate the impact of the choice of diffusion-weighting levels (b-values) on contrast-to-noise ratio and quantitative measures in prostate diffusion-weighted MRI. Study Type Retrospective and simulation based on published data. Subjects Patient cohort (21 men with Prostate Imaging-Reporting and Data System (PI-RADS) version 2 score >= 3) from a single-center study. Field Strength/Sequence 3 T/diffusion-weighted imaging with single-shot echo-planar imaging. Assessment Both clinical data and simulations based on previously acquired data were used to quantify the influence of b-value choice in normal peripheral zone (PZ) and PZ tumor lesions. For clinical data, ADC was determined for different combinations of b-values. Contrast-to-noise ratio and quantitative diffusion measures were simulated for a wide range of b-values. Statistical Tests Tissue ADC and the lesion-to-normal tissue ADC ratios of different b-value combinations were compared with paired two-tailed Student's t-tests. A P-value Findings about b-value dependence derived from clinical data and from simulations agreed with each other. Provided measurement was limited to two b-values, simulation-derived optimal b-value choices coincided with PI-RADSv2 recommendations. For two-point measurements, ADC decreased by 15% when the maximum b-value increased from 1000 to 1500 seconds/mm(2), but corresponding lesion-to-normal tissue ADC ratio showed no significant change (P = 0.86 for acquired data). Simulations with three or more measurement points produced ADCs that declined by only 8% over this range of maximum b-value. Corresponding ADC ratios declined between 2.6% (three points) and 3.8% (21 points). Simulations also revealed an ADC reduction of about 19% with the shorter echo and diffusion time evaluated. Data Conclusion The comprehensive assessment of b-value dependence permits better formulation of protocol and analysis recommendations for obtaining reproducible results in prostate cancer diffusion-weighted MRI. Level of Evidence 4 Technical Efficacy Stage 2
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| 21. |
- Maier, Stefan, et al.
(författare)
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Sb-5s lone pair dynamics and collinear magnetic ordering in Ba2FeSbSe5
- 2021
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Ingår i: Physical Review B. - : American Physical Society (APS). - 2469-9950 .- 2469-9969. ; 103:5
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Tidskriftsartikel (refereegranskat)abstract
- Neutron diffraction and x-ray pair distribution function experiments were performed to investigate the magnetic and local crystal structures of Ba2FeSbSe5 and to compare them with the average (i.e., long range) structural model previously obtained by single-crystal x-ray diffraction. Changes in the local crystal structure (i.e., in the second coordination sphere) are observed upon cooling from 295 to 95 K, resulting in deviations from the average (i.e., long range) crystal structure. In this paper, we demonstrate that these observations cannot be explained by local or long-range magnetoelastic effects involving Fe-Fe correlations. Instead, we found that the observed differences between local and average crystal structure can be explained by Sb-5s lone pair dynamics. We also find that, below the Ned temperature (T-N = 58 K), the two distinct magnetic Fe3+ sites order collinearly, such that a combination of antiparallel and parallel spin arrangements along the b axis results. The nearest-neighbor arrangement (J(1) = 6 angstrom) is fully antiferromagnetic, while next-nearest-neighbor interactions are ferromagnetic in nature.
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| 22. |
- Mattsson, Niklas, et al.
(författare)
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Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimers disease
- 2018
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Ingår i: Alzheimer's & Dementia. - : ELSEVIER SCIENCE INC. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Apolipoprotein E (APOE) epsilon 4 is the major genetic risk factor for Alzheimers disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P amp;lt;.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimers Association. Published by Elsevier Inc. All rights reserved.
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| 23. |
- Mattsson, Niklas, et al.
(författare)
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Prevalence of the apolipoprotein E ε4 allele in amyloid β positive subjects across the spectrum of Alzheimer's disease
- 2018
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 14:7, s. 913-924
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology. Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aβ+ cognitively normal and Aβ+ mild cognitive impairment (P <.05) but not in Aβ+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location.
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| 24. |
- Palme, Tina, et al.
(författare)
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Laboratory feeding experiments - investigating respiration rates of the benthic foraminifer Nonionella sp. T1
- 2023
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Ingår i: International Congress FORAMS2023, Perugia, Italy, 25-30th June 2023.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Benthic foraminifera are important components of marine ecosystems, contributing to biogeochemical cycling and serving as indicators of environmental change. Their behaviour under different environmental conditions is of importance for the study of paleoclimate due to their extensive use as paleoproxies. Gaining knowledge of their role in energy and nutrient flows leads to a better understanding of ecosystem functioning. In this study we investigated respiration rates of the potentially invasive benthic foraminifer Nonionella sp. T1 originating from sediments within the Gullmar Fjord and cultivated in artificial sea water (ASW) in the laboratory at the University of Vienna. In order to assess the flux of organic carbon within an organism both oxygen respiration and carbon assimilation need to be considered. A non-invasive method was used to analyze oxygen respiration rates. The method involved placing an Oxygen Sensor Spot in a small, 2.5 ml airtight glass vial alongside the foraminifera. Oxygen concentrations under dark and light conditions were documented using an Oxygen Microsensor. We used a large number (n = 100 per sample, triplicates measured) of cleaned, living specimen. Respiration rates are given in nl O2/h calculated for biovolume (μm3) which was assessed for each individual using photo microscopy. For the purpose of quantifying CO2 production from foraminiferal respiration samples were additionally analysed via Cavity Ring-Down Spectroscopy (CRDS) which detects trace metals and measures isotopic ratios from a gas phase. In order to more clearly trace the carbon signal from the foraminifera within this experimental setup they were fed with freeze-dried 13C-labelled diatoms (Phaeodactylum tricornutum) prior to the CO2 measurements. Our results from the Oxygen Microsensor show a consistent respiratory activity for Nonionella sp. T1 by a significant (r2 ≥ 0.98) linear decrease in oxygen content over time (~ 7 h). The oxygen respiration rates measured at 7.37 x 10-7 to 3.32 x 10-6 nl O2/μm3/h under dark conditions fall within the upper range of previously observed foraminiferal respiration rates. With most other studies using much less specimen for measurements due to their focus on the relation between respiration rates and individual biovolume a direct comparison is difficult. Further, first results from CRDS analysis show detectable amounts of CO2 release from foraminiferal respiration and more results are needed. Combining these findings our research contributes to a better understanding of the metabolic processes and the ecological role of the potentially invasive foraminifer Nonionella sp. T1. Quantifying respiration rates using significant sample sizes supports the continuous evaluation of the contribution of benthic foraminifera to O2 consumption and CO2 production within benthic communities.
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| 25. |
- Poelzl, Gerhard, et al.
(författare)
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Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post-discharge period : The multinational randomized LeoDOR trial
- 2023
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Ingår i: European Journal of Heart Failure. - : John Wiley & Sons. - 1388-9842 .- 1879-0844. ; 25:11, s. 2007-2017
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Tidskriftsartikel (refereegranskat)abstract
- Aim The LeoDOR trial explored the efficacy and safety of intermittent levosimendan therapy in the vulnerable phase following a hospitalization for acute heart failure (HF) Methods and results In this prospective multicentre, double-blind, two-armed trial, patients with advanced HF were randomized 2:1 at the end of an index hospitalization for acute HF to intermittent levosimendan therapy or matching placebo for 12weeks. All patients had left ventricular ejection fraction (LVEF) =30% during index hospitalization. Levosimendan was administered according to centre preference either as 6 h infusion at a rate of 0.2 mu g/kg/min every 2weeks, or as 24 h infusion at a rate of 0.1 mu g/kg/min every 3weeks. The primary efficacy assessment after 14weeks was based on a global rank score consisting of three hierarchical groups. Secondary clinical endpoints included the composite risk of tiers 1 and 2 at 14 and 26weeks, respectively. Due to the COVID-19 pandemic, the planned number of patients could not be recruited. The final modified intention-to-treat analysis included 145 patients (93 in the combined levosimendan arm, 52 in the placebo arm), which reduced the statistical power to detect a 20% risk reduction in the primary endpoint to 60%. Compared with placebo, intermittent levosimendan had no significant effect on the primary endpoint: the mean rank score was 72.55 for the levosimendan group versus 73.81 for the placebo group (p= 0.863). However, there was a signal towards a higher incidence of the individual clinical components of the primary endpoint in the levosimendan group versus the placebo group both after 14weeks (hazard ratio [HR] 2.94, 95% confidence interval [CI] 1.12- 7.68; p= 0.021) and 26weeks (HR 1.64, 95% CI 0.87- 3.11; p= 0.122). Among patients recently hospitalized with HF and reduced LVEF, intermittent levosimendan therapy did not improve post-hospitalization clinical stability. [GRAPHICS.]
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| 26. |
- Thienel, Manuela, et al.
(författare)
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Immobility-associated thromboprotection is conserved across mammalian species from bear to human
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6641, s. 178-187
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Tidskriftsartikel (refereegranskat)abstract
- Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a major cause of morbidity and mortality. Short-term immobility-related conditions are a major risk factor for the development of VTE. Paradoxically, long-term immobilized free-ranging hibernating brown bears and paralyzed spinal cord injury (SCI) patients are protected from VTE. We aimed to identify mechanisms of immobility-associated VTE protection in a cross-species approach. Mass spectrometry-based proteomics revealed an antithrombotic signature in platelets of hibernating brown bears with heat shock protein 47 (HSP47) as the most substantially reduced protein. HSP47 down-regulation or ablation attenuated immune cell activation and neutrophil extracellular trap formation, contributing to thromboprotection in bears, SCI patients, and mice. This cross-species conserved platelet signature may give rise to antithrombotic therapeutics and prognostic markers beyond immobility-associated VTE.
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| 27. |
- Vos, Stephanie J. B., et al.
(författare)
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Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage
- 2015
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 138:5, s. 1327-1338
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Tidskriftsartikel (refereegranskat)abstract
- Three sets of research criteria are available for diagnosis of Alzheimer's disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognitive impairment (n = 1607), 766 of whom had both amyloid and neuronal injury markers, were recruited from 13 cohorts. We used cognitive test performance and available biomarkers to classify subjects as prodromal Alzheimer's disease according to International Working Group-1 and International Working Group-2 criteria and in the high Alzheimer's disease likelihood group, conflicting biomarker groups (isolated amyloid pathology or suspected non-Alzheimer pathophysiology), and low Alzheimer's disease likelihood group according to the National Institute of Ageing-Alzheimer Association criteria. Outcome measures were the proportion of subjects with Alzheimer's disease at the mild cognitive impairment stage and progression to Alzheimer's disease-type dementia. We performed survival analyses using Cox proportional hazards models. According to the International Working Group-1 criteria, 850 (53%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 50% compared to 21% for subjects without prodromal Alzheimer's disease. According to the International Working Group-2 criteria, 308 (40%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 61% compared to 22% for subjects without prodromal Alzheimer's disease. According to the National Institute of Ageing-Alzheimer Association criteria, 353 (46%) subjects were in the high Alzheimer's disease likelihood group, 49 (6%) in the isolated amyloid pathology group, 220 (29%) in the suspected non-Alzheimer pathophysiology group, and 144 (19%) in the low Alzheimer's disease likelihood group. The 3-year progression rate to Alzheimer's disease-type dementia was 59% in the high Alzheimer's disease likelihood group, 22% in the isolated amyloid pathology group, 24% in the suspected non-Alzheimer pathophysiology group, and 5% in the low Alzheimer's disease likelihood group. Our findings support the use of the proposed research criteria to identify Alzheimer's disease at the mild cognitive impairment stage. In clinical settings, the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis. For clinical trials, selection of subjects in the National Institute of Ageing-Alzheimer Association high Alzheimer's disease likelihood group or the International Working Group-2 prodromal Alzheimer's disease group could be considered.
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| 28. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 29. |
- Wang, Xi, et al.
(författare)
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Self-Constructed Multiple Plasmonic Hotspots on an Individual Fractal to Amplify Broadband Hot Electron Generation
- 2021
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 15:6, s. 10553-10564
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Tidskriftsartikel (refereegranskat)abstract
- Plasmonic nanoparticles are ideal candidates for hot-electron-assisted applications, but their narrow resonance region and limited hotspot number hindered the energy utilization of broadband solar energy. Inspired by tree branches, we designed and chemically synthesized silver fractals, which enable self-constructed hotspots and multiple plasmonic resonances, extending the broadband generation of hot electrons for better matching with the solar radiation spectrum. We directly revealed the plasmonic origin, the spatial distribution, and the decay dynamics of hot electrons on the single-particle level by using ab initio simulation, dark-field spectroscopy, pump–probe measurements, and electron energy loss spectroscopy. Our results show that fractals with acute tips and narrow gaps can support broadband resonances (400–1100 nm) and a large number of randomly distributed hotspots, which can provide unpolarized enhanced near field and promote hot electron generation. As a proof-of-concept, hot-electron-triggered dimerization of p-nitropthiophenol and hydrogen production are investigated under various irradiations, and the promoted hot electron generation on fractals was confirmed with significantly improved efficiency.
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