| 1. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 3. |
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| 4. |
- Binder, G, et al.
(author)
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GHD Diagnostics in Europe and the US: An Audit of National Guidelines and Practice
- 2020
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In: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 92:3, s. 150-156
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Journal article (peer-reviewed)abstract
- <b><i>Introduction:</i></b> Almost 20 years after the first international guidelines on the diagnosis and treatment of GHD have been published, clinical practice varies significantly. The low accuracy of endocrine tests for GHD and the burden caused by ineffective treatment of individual patients were strong motives for national endocrine societies to set up national guidelines regarding how to diagnose GHD in childhood. This audit aims to review the current state and identify common changes, which may improve the diagnostic procedure. <b><i>Methods:</i></b> A group of eight German pediatric endocrinologists contacted eight pediatric endocrinologists from Spain, France, Poland, the UK, the Netherlands, Denmark, Italy, and the US. Each colleague responded as a representative for the own country to a detailed questionnaire containing 22 open questions about national rules, guidelines, and practice with respect to GHD diagnostics and GH prescription. The results were presented and discussed in a workshop and then documented in this study which was reviewed by all participants. <b><i>Results:</i></b> National guidelines are available in 7 of 9 countries. GH is prescribed by pediatric endocrinologists in most countries. Some countries have established boards that review and monitor prescriptions. Preferred GH stimulation tests and chosen cutoffs vary substantially. Overall, a trend to lowering the GH cutoff was identified. Priming is becoming more popular and now recommended in 5 out of 9 countries; however, with different protocols. The definition of pretest-conditions that qualify the patient to undergo GH testing varies substantially in content and strictness. The most frequently used clinical sign is low height velocity, but definition varies. Height, IGF-1, and bone age are additional parameters recommended in some countries. <b><i>Conclusions:</i></b> GHD diagnostics varies substantially in eight European countries and in the US. It seems appropriate to undertake further efforts to harmonize endocrine diagnostics in Europe and the US based on available scientific evidence.
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| 5. |
- Holmén, Jessica, 1971, et al.
(author)
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Mucins and their O-Glycans from human bronchial epithelial cell cultures.
- 2004
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In: American journal of physiology. Lung cellular and molecular physiology. - : American Physiological Society. - 1040-0605 .- 1522-1504. ; 287:4
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Journal article (peer-reviewed)abstract
- A longstanding question in obstructive airway disease is whether observed changes in mucin composition and/or posttranslational glycosylation are due to genetic or to environmental factors. We tested whether the mucins secreted by second-passage primary human bronchial epithelial cell cultures derived from noncystic fibrosis (CF) or CF patients have intrinsically different specific mucin compositions, and whether these mucins are glycosylated differently. Both CF and non-CF cultures produced MUC5B, predominantly, as judged by quantitative agarose gel Western blots with mucin-specific antibodies: MUC5B was present at approximately 10-fold higher levels than MUC5AC, consistent with our previous mRNA studies (Bernacki SH, Nelson AL, Abdullah L, Sheehan JK, Harris A, William DC, and Randell SH. Am J Respir Cell Mol Biol 20: 595-604, 1999). O-linked oligosaccharides released from purified non-CF and CF mucins and studied by HPLC mass spectrometry had highly variable glycan structures, and there were no observable differences between the two groups. Hence, there were no differences in either the specific mucins or their O-glycans that correlated with the CF phenotype under the noninfected/noninflammatory conditions of cell culture. We conclude that the differences observed in the mucins sampled directly from patients are most likely due to environmental factors relating to infection and/or inflammation.
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| 6. |
- McGenity, Clare, et al.
(author)
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Survey of liver pathologists to assess attitudes towards digital pathology and artificial intelligence
- 2023
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In: Journal of Clinical Pathology. - : BMJ PUBLISHING GROUP. - 0021-9746 .- 1472-4146.
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Journal article (peer-reviewed)abstract
- AimsA survey of members of the UK Liver Pathology Group (UKLPG) was conducted, comprising consultant histopathologists from across the UK who report liver specimens and participate in the UK National Liver Pathology External Quality Assurance scheme. The aim of this study was to understand attitudes and priorities of liver pathologists towards digital pathology and artificial intelligence (AI). MethodsThe survey was distributed to all full consultant members of the UKLPG via email. This comprised 50 questions, with 48 multiple choice questions and 2 free-text questions at the end, covering a range of topics and concepts pertaining to the use of digital pathology and AI in liver disease. ResultsForty-two consultant histopathologists completed the survey, representing 36% of fully registered members of the UKLPG (42/116). Questions examining digital pathology showed respondents agreed with the utility of digital pathology for primary diagnosis 83% (34/41), second opinions 90% (37/41), research 85% (35/41) and training and education 95% (39/41). Fatty liver diseases were an area of demand for AI tools with 80% in agreement (33/41), followed by neoplastic liver diseases with 59% in agreement (24/41). Participants were concerned about AI development without pathologist involvement 73% (30/41), however, 63% (26/41) disagreed when asked whether AI would replace pathologists. ConclusionsThis study outlines current interest, priorities for research and concerns around digital pathology and AI for liver pathologists. The majority of UK liver pathologists are in favour of the application of digital pathology and AI in clinical practice, research and education.
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| 7. |
- Pemberton, J. S., et al.
(author)
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CGM accuracy: Contrasting CE marking with the governmental controls of the USA (FDA) and Australia (TGA): A narrative review
- 2023
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In: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 25:4, s. 916-939
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Journal article (peer-reviewed)abstract
- The National Institute for Clinical Excellence updated guidance for continuous glucose monitoring (CGM) in 2022, recommending that CGM be available to all people living with type 1 diabetes. Manufacturers can trade in the UK with Conformite Europeenne (CE) marking without an initial national assessment. The regulatory process for CGM CE marking, in contrast to the Food and Drug Administration (FDA) and Australian Therapeutic Goods Administration (TGA) process, is described. Manufacturers operating in the UK provided clinical accuracy studies submitted for CE marking. Critical appraisal of the studies shows several CGM devices have CE marking for wide-ranging indications beyond available data, unlike FDA and TGA approval. The FDA and TGA use tighter controls, requiring comprehensive product-specific clinical data evaluation. In 2018, the FDA published the integrated CGM (iCGM) criteria permitting interoperability. Applying the iCGM criteria to clinical data provided by manufacturers trading in the UK identified several study protocols that minimized glucose variability, thereby improving CGM accuracy on all metrics. These results do not translate into real-life performance. Furthermore, for many CGM devices available in the UK, accuracy reported in the hypoglycaemic range is below iCGM standards, or measurement is absent. We offer a framework to evaluate CGM accuracy studies critically. The review concludes that FDA- and TGA-approved indications match the available clinical data, whereas CE marking indications can have discrepancies. The UK can bolster regulation with UK Conformity Assessed marking from January 2025. However, balanced regulation is needed to ensure innovation and timely technological access are not hindered.
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| 8. |
- Schiffer, Christian, et al.
(author)
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Structural inheritance in the North Atlantic
- 2020
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In: Earth-Science Reviews. - : Elsevier BV. - 0012-8252 .- 1872-6828. ; 206
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Research review (peer-reviewed)abstract
- The North Atlantic, extending from the Charlie Gibbs Fracture Zone to the north Norway-Greenland-Svalbard margins, is regarded as both a classic case of structural inheritance and an exemplar for the Wilson-cycle concept. This paper examines different aspects of structural inheritance in the Circum-North Atlantic region: 1) as a function of rejuvenation from lithospheric to crustal scales, and 2) in terms of sequential rifting and opening of the ocean and its margins, including a series of failed rift systems. We summarise and evaluate the role of fundamental lithospheric structures such as mantle fabric and composition, lower crustal inhomogeneities, orogenic belts, and major strike-slip faults during breakup. We relate these to the development and shaping of the NE Atlantic rifted margins, localisation of magmatism, and microcontinent release. We show that, although inheritance is common on multiple scales, the Wilson Cycle is at best an imperfect model for the Circum-North Atlantic region. Observations from the NE Atlantic suggest depth dependency in inheritance (surface, crust, mantle) with selective rejuvenation depending on time-scales, stress field orientations and thermal regime. Specifically, post-Caledonian reactivation to form the North Atlantic rift systems essentially followed pre-existing orogenic crustal structures, while eventual breakup reflected a change in stress field and exploitation of a deeper-seated, lithospheric-scale shear fabrics. We infer that, although collapse of an orogenic belt and eventual transition to a new ocean does occur, it is by no means inevitable.
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| 9. |
- Schiffer, Christian, et al.
(author)
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Vp/Vs ratios in the Parnaíba Basin from joint active-passive seismic analysis : Implications for continental amalgamation and basin formation
- 2021
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In: Tectonophysics. - : Elsevier. - 0040-1951 .- 1879-3266. ; 801
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Journal article (peer-reviewed)abstract
- The Phanerozoic intracontinental Parnaíba Basin in northeast Brazil lies atop crust composed of Archaean to Mesoproterozoic cratonic blocks and Neoproterozoic mobile belts. Recently, active and passive source geophysical surveys characterised the crustal structure beneath the basin. We use information from published active-source seismic and new, coincident receiver function (RF) data to obtain Vp/Vs ratios for sedimentary and crustal structure and make inferences about crustal compositions and tectonic evolution. In our approach, sedimentary and crustal Vp/Vs ratios are adjusted to match common conversion point (CCP) images of RFs and known Moho and basement geometry. We use a P-wave model from published wide-angle reflection/refraction (WARR) seismics, and structural features from a deep seismic reflection (DSR) profile. CCP images of the primary RF conversions were used to model the crust, whilst conversions of multiples were used for the sediment-basement interface. The maximum uncertainties in Vp/Vs are estimated to be 0.15 for the basin and 0.03 for the crust. Vp/Vs ratios in the basin were estimated between 1.7 and 2.2. Lower values correlate with the exposure of older units primarily in the east of the basin, whilst higher values coincide with exposed younger units of the Parnaíba Basin. The obtained crustal Vp/Vs ratios between 1.73 and 1.81 support the previously published segmentation of the crust. In particular, we identified three regions of elevated Vp/Vs ratios, which can be related to proposed Neoproterozoic suture zones underlying the Parnaíba Basin, as well as high velocity lower crust beneath. The high Vp/Vs ratios can be explained by mafic compositions, for example metamorphosed or intruded crust, or fluids and sedimentary rocks entrained into highly deformed crust, typical for modifications related to suture zones. These new deep geophysical models provide important and complementary evidence for crustal amalgamation and the formation of the Parnaíba Basin.
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