| 1. |
|
|
| 2. |
|
|
| 3. |
- Khatri, C, et al.
(författare)
-
Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
-
Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
-
Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Ageron, M., et al.
(författare)
-
The ANTARES optical beacon system
- 2007
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 578:3, s. 498-509
-
Tidskriftsartikel (refereegranskat)abstract
- ANTARES is a neutrino telescope being deployed in the Mediterranean Sea. It consists of a three-dimensional array of photomultiplier tubes that can detect the Cherenkov light induced by charged particles produced in the interactions of neutrinos with the surrounding medium. High angular resolution can be achieved, in particular, when a muon is produced, provided that the Cherenkov photons are detected with sufficient timing precision. Considerations of the intrinsic time uncertainties stemming from the transit time spread in the photomultiplier tubes and the mechanism of transmission of light in sea water lead to the conclusion that a relative time accuracy of the order of 0.5 ns is desirable. Accordingly, different time calibration systems have been developed for the ANTARES telescope. In this article, a system based on Optical Beacons, a set of external and well-controlled pulsed light sources located throughout the detector, is described. This calibration system takes into account the optical properties of sea water, which is used as the detection volume of the ANTARES telescope. The design, tests, construction and first results of the two types of beacons, LED and laser-based, are presented. (C) 2007 Elsevier B.V. All rights reserved.
|
|
| 9. |
- Aguilar, J. A., et al.
(författare)
-
First results of the instrumentation line for the deep-sea ANTARES neutrino telescope
- 2006
-
Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 26:4-5, s. 314-324
-
Tidskriftsartikel (refereegranskat)abstract
- In 2005, the ANTARES Collaboration deployed and operated at a depth of 2500 m a so-called Mini Instrumentation Line equipped with Optical Modules (MILOM) at the ANTARES site. The various data acquired during the continuous operation from April to December 2005 of the MILOM confirm the satisfactory performance of the Optical Modules, their front-end electronics and readout system. as well as the calibration devices of the detector. The in situ measurement of the Optical Module time response yields a resolution better than 0.5 ns. The performance of the acoustic positioning system, which enables the spatial reconstruction of the ANTARES detector with a precision of about 10 cm, is verified. These results demonstrate that with the full ANTARES neutrino telescope the design angular resolution of better than 0.3 degrees can be realistically achieved.
|
|
| 10. |
- Aguilar, J. A., et al.
(författare)
-
The data acquisition system for the ANTARES neutrino telescope
- 2007
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 570:1, s. 107-116
-
Tidskriftsartikel (refereegranskat)abstract
- The ANTARES neutrino telescope is being constructed in the Mediterranean Sea. It consists of a large three-dimensional array of photo-multiplier tubes. The data acquisition system of the detector takes care of the digitisation of the photo-multiplier tube signals, data transport, data filtering, and data storage. The detector is operated using a control program interfaced with all elements. The design and the implementation of the data acquisition system are described. (c) 2006 Elsevier B.V. All rights reserved.
|
|
| 11. |
- Aguilar, J A, et al.
(författare)
-
Study of large hemispherical photomultiplier tubes for the ANTARES neutrino telescope
- 2005
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 555:1-2, s. 132-141
-
Tidskriftsartikel (refereegranskat)abstract
- The ANTARES neutrino telescope, to be immersed depth in the Mediterranean Sea, will consist of a three-dimensional matrix of 900 large area photomultiplier tubes housed in pressure-resistant glass spheres. The selection of the optimal photomultiplier was a critical step for the project and required an intensive phase of tests and developments carried out in close collaboration with the main manufacturers worldwide. This paper provides an overview of the tests performed by the collaboration and describes in detail the features of the photomultiplier tube chosen for ANTARES. (c) 2005 Elsevier B.V. All rights reserved.
|
|
| 12. |
- Ageron, M., et al.
(författare)
-
Studies of a full-scale mechanical prototype line for the ANTARES neutrino telescope and tests of a prototype instrument for deep-sea acoustic measurements
- 2007
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 581:3, s. 695-708
-
Tidskriftsartikel (refereegranskat)abstract
- full-scale mechanical prototype line was deployed to a depth of 2500 m to test the leak tightness of the electronics containers and the pressure-resistant properties of an electromechanical cable under evaluation for use in the ANTARES deep-sea neutrino telescope. During a month-long immersion study, line parameter data were taken using miniature autonomous data loggers and shore-based optical time domain reflectometry. Details of the mechanical prototype line, the electromechanical cable and data acquisition are presented. Data taken during the immersion study revealed deficiencies in the pressure resistance of the electromechanical cable terminations at the entry points to the electronics containers. The improvements to the termination, which have been integrated into subsequent detection lines, are discussed. The line also allowed deep-sea acoustic measurements with a prototype hydrophone system. The technical setup of this system is described, and the first results of the data analysis are presented. (c) 2007 Elsevier B.V. All rights reserved.
|
|
| 13. |
- Aguilar, J A, et al.
(författare)
-
Transmission of light in deep sea water at the site of the ANTARES neutrino telescope
- 2005
-
Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 23:1, s. 131-155
-
Tidskriftsartikel (refereegranskat)abstract
- The ANTARES neutrino telescope is a large photomultiplier array designed to detect neutrino-induced upward-going muons by their Cherenkov radiation. Understanding the absorption and scattering of light in the deep Mediterranean is fundamental to optimising the design and performance of the detector. This paper presents measurements of blue and UV light transmission at the ANTARES site taken between 1997 and 2000. The derived values for the scattering length and the angular distribution of particulate scattering were found to be highly correlated, and results are therefore presented in terms of an absorption length;,ab, and an effective scattering length lambda(sct)(eff). The values for blue (UV) light are found to be lambda(abs) similar or equal to 60(26) m, lambda(sct)(eff similar or equal to) 265(122) m, with significant (similar to15%) time variability. Finally, the results of ANTARES simulations showing the effect of these water properties on the anticipated performance of the detector are presented. (C) 2004 Elsevier B.V. All rights reserved.
|
|
| 14. |
- Mercuri, E., et al.
(författare)
-
Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study
- 2020
-
Ingår i: Journal of Comparative Effectiveness Research. - : Becaris Publishing Limited. - 2042-6305 .- 2042-6313. ; 9:5, s. 341-360
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype-phenotype/-ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan-Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p <= 0.05). There were no DMD genotype-phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.
|
|
| 15. |
- Retamozo, S., et al.
(författare)
-
Influence of the age at diagnosis in the disease expression of primary Sjogren's syndrome : Analysis of 12,753 patients from the Sjogren Big Data Consortium
- 2021
-
Ingår i: Clinical and Experimental Rheumatology. - : CLINICAL & EXPER RHEUMATOLOGY. - 0392-856X .- 1593-098X. ; 39:6, s. S166-S174
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. To analyse how the main components of the disease phenotype (sicca symptoms, diagnostic tests, immunological markers and systemic disease) can be driven by the age at diagnosis of primary Sjogren's syndrome (pSS).Methods. By January 2021, the participant centres had included 12,753 patients from 25 countries that fulfilled the 2002/2016 classification criteria for pSS. The age at diagnosis was defined as the time when the attending physician confirmed fulfilment of the criteria. Patients were clustered according to age at diagnosis. 50 clusters with more than 100 observations (from 27 to 76 years) were used to study the influence of the age at diagnosis in the disease expression.Results. There was a consistent increase in the frequency of oral dryness according to the age at diagnosis, with a frequency of <90% in patients diagnosed at the youngest ages and >95% in those diagnosed at the oldest ages. The smooth curves that best fitted a linear model were the frequency of dry mouth (adjusted R-2 0.87) and the frequency of abnormal oral tests (adjusted R-2 0.72). Therefore, for each 1-year increase in the age at diagnosis, the frequency of dry mouth increased by 0.13%, and the frequency of abnormal oral diagnostic tests by 0.11%. There was a consistent year-by-year decrease in the frequency of all autoantibodies and immunological markers except for cryoglobulins. According to the linear models, for each 1-year increase in the age at diagnosis, the frequency of a positive result decreased by 0.57% (for anti-Ro antibodies), 0.47% (for RF) and 0.42% (for anti-La antibodies). The ESSDAI domains which showed a more consistent decrease were glandular and lymph node involvement (for each 1-year increase in the age at diagnosis, the frequency of activity decreased by 0.18%), and constitutional, cutaneous, and haematological involvements (the frequency decreased by 0.09% for each 1-year increase). In contrast, other domains showed an ascending pattern, especially pulmonary involvement (for each 1-year increase in the age at diagnosis, the frequency of activity increased by 0.22%), and peripheral nerve involvement (the frequency increased by 0.09% for each 1-year increase).Conclusion. The influence of the age at diagnosis on the key phenotypic features of pSS is strong, and should be considered critical not only for designing a personalised diagnostic approach, but also to be carefully considered when analysing the results of diagnostic tests and immunological parameters, and when internal organ involvement is suspected at diagnosis.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Flores-Chavez, A., et al.
(författare)
-
Influence of exposure to climate-related hazards in the phenotypic expression of primary Sjögren's syndrome
- 2023
-
Ingår i: Clinical and Experimental Rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 41:12, s. 2437-2447
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To analyse how the key components at the time of diagnosis of the Sjogren's phenotype (epidemiological profile, sicca symptoms, and systemic disease) can be influenced by the potential exposure to climate-related natural hazards. Methods For the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Climate-related hazards per country were defined according to the OECD and included seven climate-related hazard types: extreme temperature, extreme precipitation, drought, wildfire, wind threats, river flooding, and coastal flooding. Climatic variables were defined as dichotomous variables according to whether each country is ranked among the ten countries with the most significant exposure. Results After applying data-cleaning techniques and excluding people from countries not included in the OECD climate rankings, the database study analysed 16,042 patients from 23 countries. The disease was diagnosed between 1 and 3 years earlier in people living in countries included among the top 10 worst exposed to extreme precipitation, wildfire, wind threats, river flooding, and coastal flooding. A lower frequency of dry eyes was observed in people living in countries exposed to wind threats, river flooding, and coastal flooding, with a level of statistical association being classified as strong (p<0.0001 for the three variables). The frequency of dry mouth was significantly lower in people living in countries exposed to river flooding (p<0.0001) and coastal flooding (p<0.0001). People living in countries included in the worse climate scenarios for extreme temperature (p<0.0001) and river flooding (p<0.0001) showed a higher mean ESSDAI score in comparison with people living in no-risk countries. In contrast, those living in countries exposed to worse climate scenarios for wind threats (p<0.0001) and coastal flooding (p<0.0001) showed a lower mean ESSDAI score in comparison with people living in no-risk countries. Conclusion Local exposure to extreme climate-related hazards plays a role in modulating the presentation of Sjogren across countries concerning the age at which the disease is diagnosed, the frequency of dryness, and the degree of systemic activity.
|
|
| 19. |
|
|
| 20. |
- Brito-Zeron, P., et al.
(författare)
-
Exposure to air pollution as an environmental determinant of how Sjögren's disease is expressed at diagnosis
- 2023
-
Ingår i: Clinical and Experimental Rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 41:12, s. 2448-2457
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo analyse how the potential exposure to air pollutants can influence the key components at the time of diagnosis of Sjogren's phenotype (epidemiological profile, sicca symptoms, and systemic disease). MethodsFor the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Air pollution indexes per country were defined according to the OECD (1990-2021), including emission data of nitrogen and sulphur oxides (NO/SO), particulate matter (PM2.5 and 1.0), carbon monoxide (CO) and volatile organic compounds (VOC) calculated per unit of GDP, Kg per 1000 USD.ResultsThe results of the chi-square tests of independence for each air pollutant with the frequency of dry eyes at diagnosis showed that, except for one, all variables exhibited p-values <0.0001. The most pronounced disparities emerged in the dry eye prevalence among individuals inhabiting countries with the highest NO/SO exposure, a surge of 4.61 percentage points compared to other countries, followed by CO (3.59 points), non-methane (3.32 points), PM2.5 (3.30 points), and PM1.0 (1.60 points) exposures. Concerning dry mouth, individuals residing in countries with worse NO/SO exposures exhibited a heightened frequency of dry mouth by 2.05 percentage points (p<0.0001), followed by non-methane exposure (1.21 percentage points increase, p=0.007). Individuals inhabiting countries with the worst NO/SO, CO, and PM2.5 pollution levels had a higher mean global ESSDAI score than those in lower-risk nations (all p-values <0.0001). When systemic disease was stratified according to DAS into low, moderate, and high systemic activity levels, a heightened proportion of individuals manifesting moderate/severe systemic activity was observed in countries with worse exposures to NO/SO, CO, and PM2.5 pollutant levels. ConclusionFor the first time, we suggest that pollution levels could influence how SjD appears at diagnosis in a large international cohort of patients. The most notable relationships were found between symptoms (dryness and general body symptoms) and NO/SO, CO, and PM2.5 levels.
|
|
| 21. |
- Byrne, L. M., et al.
(författare)
-
Cerebrospinal fluid neurogranin and TREM2 in Huntington's disease
- 2018
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Biomarkers of Huntington's disease (HD) in cerebrospinal fluid (CSF) could be of value in elucidating the biology of this genetic neurodegenerative disease, as well as in the development of novel therapeutics. Deranged synaptic and immune function have been reported in HD, and concentrations of the synaptic protein neurogranin and the microglial protein TREM2 are increased in other neurodegenerative diseases. We therefore used ELISAs to quantify neurogranin and TREM2 in CSF samples from HD mutation carriers and controls. CSF neurogranin concentration was not significantly altered in HD compared to controls, nor was it significantly associated with disease burden score, total functional capacity or motor score. An apparent increase in CSF TREM2 in manifest HD was determined to be due to increasing TREM2 with age. After age adjustment, there was no significant alteration of TREM2 in either HD group, nor any association with motor, functional or cognitive score, or brain volume quantified by MRI. Both analyses were well-powered, and sample size calculations indicated that several thousand samples per group would be needed to prove that disease-associated alterations do in fact exist. We conclude that neither neurogranin nor TREM2 is a useful biofluid biomarker for disease processes in Huntington's disease.
|
|
| 22. |
- Byrne, L. M., et al.
(författare)
-
Evaluation of mutant huntingtin and neurofilament proteins as potential markers in Huntington's disease
- 2018
-
Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 10:458
-
Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is a genetic progressive neurodegenerative disorder, caused by a mutation in the HTT gene, for which there is currently no cure. The identification of sensitive indicators of disease progression and therapeutic outcome could help the development of effective strategies for treating HD. We assessed mutant huntingtin (mHTT) and neurofilament light (NfL) protein concentrations in cerebrospinal fluid (CSF) and blood in parallel with clinical evaluation and magnetic resonance imaging in premanifest and manifest HD mutation carriers. Among HD mutation carriers, NfL concentrations in plasma and CSF correlated with all nonbiofluid measures more closely than did CSF mHTT concentration. Longitudinal analysis over 4 to 8 weeks showed that CSF mHTT, CSF NfL, and plasma NfL concentrations were highly stable within individuals. In our cohort, concentration of CSF mHTT accurately distinguished between controls and HD mutation carriers, whereas NfL concentration, in both CSF and plasma, was able to segregate premanifest from manifest HD. In silico modeling indicated that mHTT and NfL concentrations in biofluids might be among the earliest detectable alterations in HD, and sample size prediction suggested that low participant numbers would be needed to incorporate these measures into clinical trials. These findings provide evidence that biofluid concentrations of mHTT and NfL have potential for early and sensitive detection of alterations in HD and could be integrated into both clinical trials and the clinic.
|
|
| 23. |
- Credendino, S. C., et al.
(författare)
-
Tissue- and Cell Type-Specific Expression of the Long Noncoding RNA Klhl14-AS in Mouse
- 2017
-
Ingår i: International Journal of Genomics. - : Hindawi Limited. - 2314-436X .- 2314-4378.
-
Tidskriftsartikel (refereegranskat)abstract
- lncRNAs are acquiring increasing relevance as regulators in a wide spectrum of biological processes. The extreme heterogeneity in the mechanisms of action of these molecules, however, makes them very difficult to study, especially regarding their molecular function. A novel lncRNA has been recently identified as the most enriched transcript in mouse developing thyroid. Due to its genomic localization antisense to the protein-encoding Klhl14 gene, we named it Klhl14-AS. In this paper, we highlight that mouse Klhl14-AS produces at least five splicing variants, some of which have not been previously described. Klhl14-AS is expressed with a peculiar pattern, characterized by diverse relative abundance of its isoforms in different mouse tissues. We examine the whole expression level of Klhl14-AS in a panel of adult mouse tissues, showing that it is expressed in the thyroid, lung, kidney, testis, ovary, brain, and spleen, although at different levels. In situ hybridization analysis reveals that, in the context of each organ, Klhl14-AS shows a cell type-specific expression. Interestingly, databases report a similar expression profile for human Klhl14-AS. Our observations suggest that this lncRNA could play cell type-specific roles in several organs and pave the way for functional characterization of this gene in appropriate biological contexts.
|
|
| 24. |
- Lowe, A. J., et al.
(författare)
-
Longitudinal evaluation of proton magnetic resonance spectroscopy metabolites as biomarkers in Huntington's disease
- 2022
-
Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 4:6
-
Tidskriftsartikel (refereegranskat)abstract
- The study by Lowe et al. uses magnetic resonance spectroscopy to investigate the biomarker potential of neurochemical metabolites in Huntington's disease. Cross-sectional associations were observed between metabolites and prognostic measures; however, the absence of consistent group differences and lack of clear longitudinal change indicates limited biomarker potential in Huntington's disease. Proton magnetic resonance spectroscopy is a non-invasive method of exploring cerebral metabolism. In Huntington's disease, altered proton magnetic resonance spectroscopy-determined concentrations of several metabolites have been described; however, findings are often discrepant and longitudinal studies are lacking. Proton magnetic resonance spectroscopy metabolites may represent a source of biomarkers, thus their relationship with established markers of disease progression require further exploration to assess prognostic value and elucidate pathways associated with neurodegeneration. In a prospective single-site controlled cohort study with standardized collection of CSF, blood, phenotypic and volumetric imaging data, we used 3 T proton magnetic resonance spectroscopy in conjunction with the linear combination of model spectra method to quantify seven metabolites (total n-acetylaspartate, total creatine, total choline, myo-inositol, GABA, glutamate and glutathione) in the putamen of 59 participants at baseline (15 healthy controls, 15 premanifest and 29 manifest Huntington's disease gene expansion carriers) and 48 participants at 2-year follow-up (12 healthy controls, 13 premanifest and 23 manifest Huntington's disease gene expansion carriers). Intergroup differences in concentration and associations with CSF and plasma biomarkers; including neurofilament light chain and mutant Huntingtin, volumetric imaging markers; namely whole brain, caudate, grey matter and white matter volume, measures of disease progression and cognitive decline, were assessed cross-sectionally using generalized linear models and partial correlation. We report no significant groupwise differences in metabolite concentration at baseline but found total creatine and total n-acetylaspartate to be significantly reduced in manifest compared with premanifest participants at follow-up. Additionally, total creatine and myo-inositol displayed significant associations with reduced caudate volume across both time points in gene expansion carriers. Although relationships were observed between proton magnetic resonance spectroscopy metabolites and biofluid measures, these were not consistent across time points. To further assess prognostic value, we examined whether baseline proton magnetic resonance spectroscopy values, or rate of change, predicted subsequent change in established measures of disease progression. Several associations were found but were inconsistent across known indicators of disease progression. Finally, longitudinal mixed-effects models revealed glutamine + glutamate to display a slow linear decrease over time in gene expansion carriers. Altogether, our findings show some evidence of reduced total n-acetylaspartate and total creatine as the disease progresses and cross-sectional associations between select metabolites, namely total creatine and myo-inositol, and markers of disease progression, potentially highlighting the proposed roles of neuroinflammation and metabolic dysfunction in disease pathogenesis. However, the absence of consistent group differences, inconsistency between baseline and follow-up, and lack of clear longitudinal change suggests that proton magnetic resonance spectroscopy metabolites have limited potential as Huntington's disease biomarkers.
|
|
| 25. |
- Malapelle, Umberto, et al.
(författare)
-
Reference standards for gene fusion molecular assays on cytological samples : an international validation study
- 2023
-
Ingår i: Journal of Clinical Pathology. - : BMJ. - 0021-9746 .- 1472-4146. ; 76:1, s. 47-52
-
Tidskriftsartikel (refereegranskat)abstract
- Aims Gene fusions assays are key for personalised treatments of advanced human cancers. Their implementation on cytological material requires a preliminary validation that may make use of cell line slides mimicking cytological samples. In this international multi-institutional study, gene fusion reference standards were developed and validated. Methods Cell lines harbouring EML4(13)–ALK(20) and SLC34A2(4)–ROS1(32) gene fusions were adopted to prepare reference standards. Eight laboratories (five adopting amplicon-based and three hybridisation-based platforms) received, at different dilution points two sets of slides (slide A 50.0%, slide B 25.0%, slide C 12.5% and slide D wild type) stained by Papanicolaou (Pap) and May Grunwald Giemsa (MGG). Analysis was carried out on a total of 64 slides. Results Four (50.0%) out of eight laboratories reported results on all slides and dilution points. While 12 (37.5%) out of 32 MGG slides were inadequate, 27 (84.4%) out of 32 Pap slides produced libraries adequate for variant calling. The laboratories using hybridisation-based platforms showed the highest rate of inadequate results (13/24 slides, 54.2%). Conversely, only 10.0% (4/40 slides) of inadequate results were reported by laboratories adopting amplicon-based platforms. Conclusions Reference standards in cytological format yield better results when Pap staining and processed by amplicon-based assays. Further investigation is required to optimise these standards for MGG stained cells and for hybridisation-based approaches.
|
|
