| 1. |
- Vandenput, Liesbeth, 1974, et al.
(författare)
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Update of the fracture risk prediction tool FRAX : a systematic review of potential cohorts and analysis plan
- 2022
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 33:10, s. 2103-2136
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Forskningsöversikt (refereegranskat)abstract
- Summary: We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures.Introduction: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors.Methods: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible.Results: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed.Conclusions: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).
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| 2. |
- Milillo, A., et al.
(författare)
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Investigating Mercury's Environment with the Two-Spacecraft BepiColombo Mission
- 2020
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Ingår i: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 216:5
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Forskningsöversikt (refereegranskat)abstract
- The ESA-JAXA BepiColombo mission will provide simultaneous measurements from two spacecraft, offering an unprecedented opportunity to investigate magnetospheric and exospheric dynamics at Mercury as well as their interactions with the solar wind, radiation, and interplanetary dust. Many scientific instruments onboard the two spacecraft will be completely, or partially devoted to study the near-space environment of Mercury as well as the complex processes that govern it. Many issues remain unsolved even after the MESSENGER mission that ended in 2015. The specific orbits of the two spacecraft, MPO and Mio, and the comprehensive scientific payload allow a wider range of scientific questions to be addressed than those that could be achieved by the individual instruments acting alone, or by previous missions. These joint observations are of key importance because many phenomena in Mercury's environment are highly temporally and spatially variable. Examples of possible coordinated observations are described in this article, analysing the required geometrical conditions, pointing, resolutions and operation timing of different BepiColombo instruments sensors.
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| 3. |
- Bale, S. D., et al.
(författare)
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The FIELDS Instrument Suite for Solar Probe Plus
- 2016
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Ingår i: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 204:1-4, s. 49-82
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Forskningsöversikt (refereegranskat)abstract
- NASA's Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products.
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| 4. |
- Dunlop, R. A., et al.
(författare)
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Is Exposure to BMAA a Risk Factor for Neurodegenerative Diseases? : A Response to a Critical Review of the BMAA Hypothesis
- 2021
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Ingår i: Neurotoxicity research. - : Springer. - 1029-8428 .- 1476-3524. ; 39:1, s. 81-106
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Forskningsöversikt (refereegranskat)abstract
- In a literature survey, Chernoff et al. (2017) dismissed the hypothesis that chronic exposure to beta-N-methylamino-L-alanine (BMAA) may be a risk factor for progressive neurodegenerative disease. They question the growing scientific literature that suggests the following: (1) BMAA exposure causes ALS/PDC among the indigenous Chamorro people of Guam; (2) Guamanian ALS/PDC shares clinical and neuropathological features with Alzheimer's disease, Parkinson's disease, and ALS; (3) one possible mechanism for protein misfolds is misincorporation of BMAA into proteins as a substitute for L-serine; and (4) chronic exposure to BMAA through diet or environmental exposures to cyanobacterial blooms can cause neurodegenerative disease. We here identify multiple errors in their critique including the following: (1) their review selectively cites the published literature; (2) the authors reported favorably on HILIC methods of BMAA detection while the literature shows significant matrix effects and peak coelution in HILIC that may prevent detection and quantification of BMAA in cyanobacteria; (3) the authors build alternative arguments to the BMAA hypothesis, rather than explain the published literature which, to date, has been unable to refute the BMAA hypothesis; and (4) the authors erroneously attribute methods to incorrect studies, indicative of a failure to carefully consider all relevant publications. The lack of attention to BMAA research begins with the review's title which incorrectly refers to BMAA as a "non-essential" amino acid. Research regarding chronic exposure to BMAA as a cause of human neurodegenerative diseases is emerging and requires additional resources, validation, and research. Here, we propose strategies for improvement in the execution and reporting of analytical methods and the need for additional and well-executed inter-lab comparisons for BMAA quantitation. We emphasize the need for optimization and validation of analytical methods to ensure that they are fit-for-purpose. Although there remain gaps in the literature, an increasingly large body of data from multiple independent labs using orthogonal methods provides increasing evidence that chronic exposure to BMAA may be a risk factor for neurological illness.
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| 5. |
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| 6. |
- Lennernäs, Hans, et al.
(författare)
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Oral biopharmaceutics tools - Time for a new initiative - An introduction to the IMI project OrBiTo
- 2014
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 57:SI, s. 292-299
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Forskningsöversikt (refereegranskat)abstract
- OrBiTo is a new European project within the IMI programme in the area of oral biopharmaceutics tools that includes world leading scientists from nine European universities, one regulatory agency, one non-profit research organization, four SMEs together with scientists from twelve pharmaceutical companies. The OrBiTo project will address key gaps in our knowledge of gastrointestinal (GI) drug absorption and deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This will be achieved through novel prospective investigations to define new methodologies as well as refinement of existing tools. Extensive validation of novel and existing biopharmaceutics tools will be performed using active pharmaceutical ingredient (API), formulations and supporting datasets from industry partners. A combination of high quality in vitro or in silico characterizations of API and formulations will be integrated into physiologically based in silica biopharmaceutics models capturing the full complexity of GI drug absorption. This approach gives an unparalleled opportunity to initiate a transformational change in industrial research and development to achieve model-based pharmaceutical product development in accordance with the Quality by Design concept. Benefits include an accelerated and more efficient drug candidate selection, formulation development process, particularly for challenging projects such as low solubility molecules (BCS II and IV), enhanced and modified-release formulations, as well as allowing optimization of clinical product performance for patient benefit. In addition, the tools emerging from OrBiTo are expected to significantly reduce demand for animal experiments in the future as well as reducing the number of human bioequivalence studies required to bridge formulations after manufacturing or composition changes.
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| 7. |
- Oeding, J. F., et al.
(författare)
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A practical guide to the development and deployment of deep learning models for the Orthopedic surgeon: part I
- 2023
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 31:2, s. 382-389
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Forskningsöversikt (refereegranskat)abstract
- Deep learning has a profound impact on daily life. As Orthopedics makes use of this rapid escalation in technology, Orthopedic surgeons will need to take leadership roles on deep learning projects. Moreover, surgeons must possess an understanding of what is necessary to design and implement deep learning-based project pipelines. This review provides a practical guide for the Orthopedic surgeon to understand the steps needed to design, develop, and deploy a deep learning pipeline for clinical applications. A detailed description of the processes involved in defining the problem, building the team, acquiring and curating the data, labeling the data, establishing the ground truth, pre-processing and augmenting the data, and selecting the required hardware is provided. In addition, an overview of unique considerations involved in the training and evaluation of deep learning models is provided. This review strives to provide surgeons with the groundwork needed to identify gaps in the clinical landscape that deep learning models may be able to fill and equips them with the knowledge needed to lead an interdisciplinary team through the process of creating novel deep-learning-based solutions to fill those gaps.
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| 8. |
- D'Ambrosi, R., et al.
(författare)
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Good results after treatment of RAMP lesions in association with ACL reconstruction: a systematic review
- 2023
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 31:1, s. 358-371
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Forskningsöversikt (refereegranskat)abstract
- Purpose This study aimed to systematically evaluate the clinical, functional, and radiological outcomes, complications, and rate of return to sports among patients with RAMP lesion of the medial meniscus encountered during anterior cruciate ligament (ACL) reconstruction. Methods A systematic review was conducted based on the PRISMA guidelines. Two independent reviewers searched the PubMed, Scopus, Embase, and Cochrane Library databases using the terms "ACL" or "anterior cruciate ligament," and "RAMP lesion." The outcome measures extracted from the studies were the Short Form-12 (SF-12) in its mental and physical component (MCS and PCS), Lysholm score, Subjective IKDC, Marx Score, WOMAC Score, Tegner, Radiological changes, complications, failures and/or revision surgery, and rate of return to sports. Results The cohort of patients consisted of 1,243 participants with a mean age of 28.6 +/- 2.6. The mean postoperative follow-up was 40.9 +/- 6.3 months. A total of 1145 (92.1%) RAMP lesions were repaired with concomitant ACL reconstruction, while only 98 (7.9%) lesions were left untreated (or treated with abrasion only). The Lysholm score was used in 6 studies (in one only at final follow-up), with a significant improvement in all the studies (Lysholm(pre) 60.03 +/- 6.12; Lysholm(post) 89.9 +/- 5.0). Eight studies out of nine reported Subjective IKDC score, and a significant improvement was noted in all cases (IKDCpre 56.2 +/- 5.8. IKDCpost 84.9 +/- 3.7). Of 18 (1.4%) complications reported, 15 (1.2%) were related to RAMP/ACL surgery, and of the remaining three (0.2%) two (0.2%) were hematomas and one (0.1%) a contralateral ACL lesion. Of the 106 (8.5%) revision surgeries required, 5 (0.4%) were in non-treated lesions [two (0.2%) ACL re-ruptures and three (0.2%) medial meniscus re-injury]. In treated patients, the revision occurred for the following reasons: 75 (6.0%) meniscectomy, 14 (1.1%) meniscal suture revisions, 11 (0.9%) ACL failures and one (0.1%) arthrolysis. Conclusions It is not yet clear if, in all cases of ACL reconstruction in which a medial meniscal RAMP lesion is encountered, the lesion needs to undergo surgical repair. Accordingly, it is recommended that in the repair of all unstable medial meniscal RAMP lesions during an ACL reconstruction in cases associated with a stable RAMP lesion, the surgeon may decide on repair based on the patient profile.
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| 9. |
- Karlsson, R., et al.
(författare)
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Proteotyping: Proteomic characterization, classification and identification of microorganisms - A prospectus
- 2015
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Ingår i: Systematic and Applied Microbiology. - : Elsevier BV. - 0723-2020. ; 38:4, s. 246-257
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Forskningsöversikt (refereegranskat)abstract
- Modern microbial systematics requires a range of methodologies for the comprehensive characterization, classification and identification of microorganisms. While whole-genome sequences provide the ultimate reference for defining microbial phylogeny and taxonomy, selected biomarker-based strategies continue to provide the means for the bulk of microbial systematic studies. Proteomics, the study of the expression of genes, as well as the structure and function of the resulting proteins, offers indirect measures of genome sequence data. Recent developments in applications of proteomics for analyzing microorganisms have paralleled the growing microbial genome sequence database, as well as the evolution of mass spectrometry (MS) instrumentation and bioinformatics. MALDI-TOF MS, which generates proteomic mass patterns for 'fingerprint'-based characterizations, has provided a marked breakthrough for microbial identification. However, MALDI-TOF MS is limited in the number of targets that can be detected for strain characterization. Advanced methods of tandem mass spectrometry, in which proteins and peptides generated from proteins, are characterized and identified, using LC-MS/MS, provide the ability to detect hundreds or thousands of expressed microbial strain markers for high-resolution characterizations and identifications. Model studies demonstrate the application of proteomics-based analyses for bacterial species- and strain-level detection and identification and for characterization of environmentally relevant, metabolically diverse bacteria. Proteomics-based approaches represent an emerging complement to traditional methods of characterizing microorganisms, enabling the elucidation of the expressed biomarkers of genome sequence information, which can be applied to 'proteotyping' applications of microorganisms at all taxonomic levels. (C) 2015 Elsevier GmbH. All rights reserved.
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| 10. |
- Mabrouk, A., et al.
(författare)
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MCID and PASS in Knee Surgeries. Theoretical Aspects and Clinical Relevance References
- 2023
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 31
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Forskningsöversikt (refereegranskat)abstract
- The application and interpretation of patient-reported outcome measures (PROM), following knee injuries, pathologies, and interventions, can be challenging. In recent years, the literature has been enriched with metrics to facilitate our understanding and interpretation of these outcome measures. Two commonly utilized tools include the minimal clinically important difference (MCID) and the patient acceptable symptoms state (PASS). These measures have demonstrated clinical value, however, they have often been under- or mis-reported. It is paramount to use them to understand the clinical significance of any statistically significant results. Still, it remains important to know their caveats and limitations. In this focused report on MCID and PASS, their definitions, methods of calculations, clinical relevance, interpretations, and limitations are reviewed and presented in a simple approach.
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