| 1. |
- Abele, H., et al.
(författare)
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Particle physics at the European Spallation Source
- 2023
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Ingår i: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 1023, s. 1-84
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Forskningsöversikt (refereegranskat)abstract
- Presently under construction in Lund, Sweden, the European Spallation Source (ESS) will be the world’s brightest neutron source. As such, it has the potential for a particle physics program with a unique reach and which is complementary to that available at other facilities. This paper describes proposed particle physics activities for the ESS. These encompass the exploitation of both the neutrons and neutrinos produced at the ESS for high precision (sensitivity) measurements (searches).
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| 2. |
- Burgman, A., et al.
(författare)
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The ESSnuSB Design Study: Overview and Future Prospects
- 2023
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Ingår i: Universe. - : MDPI. - 2218-1997. ; 9:8
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Forskningsöversikt (refereegranskat)abstract
- ESSnuSB is a design study for an experiment to measure the CP violation in the leptonic sector at the second neutrino oscillation maximum using a neutrino beam driven by the uniquely powerful ESS linear accelerator. The reduced impact of systematic errors on sensitivity at the second maximum allows for a very precise measurement of the CP violating parameter. This review describes the fundamental advantages of measurement at the second maximum, the necessary upgrades to the ESS linac in order to produce a neutrino beam, the near and far detector complexes, and the expected physics reach of the proposed ESSnuSB experiment, concluding with the near future developments aimed at the project realization.
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| 3. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 4. |
- Burgman, A., et al.
(författare)
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The European Spallation Source neutrino super-beam conceptual design report
- 2022
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Ingår i: The European Physical Journal Special Topics. - : Springer Nature. - 1951-6355 .- 1951-6401. ; 231:21, s. 3779-3955
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Forskningsöversikt (refereegranskat)abstract
- A design study, named ESSνSB for European Spallation Source neutrino Super Beam, has been carried out during the years 2018–2022 of how the 5 MW proton linear accelerator of the European Spallation Source under construction in Lund, Sweden, can be used to produce the world’s most intense long-baseline neutrino beam. The high beam intensity will allow for measuring the neutrino oscillations near the second oscillation maximum at which the CP violation signal is close to three times higher than at the first maximum, where other experiments measure. This will enable CP violation discovery in the leptonic sector for a wider range of values of the CP violating phase δCPδCP and, in particular, a higher precision measurement of δCPδCP. The present Conceptual Design Report describes the results of the design study of the required upgrade of the ESS linac, of the accumulator ring used to compress the linac pulses from 2.86 ms to 1.2 μs, and of the target station, where the 5 MW proton beam is used to produce the intense neutrino beam. It also presents the design of the near detector, which is used to monitor the neutrino beam as well as to measure neutrino cross sections, and of the large underground far detector located 360 km from ESS, where the magnitude of the oscillation appearance of νe from νμ is measured. The physics performance of the ESSνSB research facility has been evaluated demonstrating that after 10 years of data-taking, leptonic CP violation can be detected with more than 5 standard deviation significance over 70% of the range of values that the CP violation phase angle δCPδCP can take and that δCPδCP can be measured with a standard error less than 8° irrespective of the measured value of δCPδCP. These results demonstrate the uniquely high physics performance of the proposed ESSνSBESSνSB research facility.
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| 5. |
- Wiltfang, J., et al.
(författare)
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Consensus Paper of the WFSBP Task Force on Biological Markers of Dementia : The role of CSF and blood analysis in the early and differential diagnosis of dementia
- 2009
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Ingår i: Revista de Psiquiatria Clinica. - 0101-6083. ; 36, s. 1-16
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Forskningsöversikt (refereegranskat)abstract
- Aging of population, and increasing life expectancy result in an increasing number of patients with dementia. This symptom can be a part of a completely curable disease of the central nervous system (e.g, neuroinflammation), or a disease currently considered irreversible (e.g, Alzheimer's disease, AD). In the latter case, several potentially successful treatment approaches are being tested now, demanding reasonable standards of pre-mortem diagnosis. Cerebrospinal fluid and serum analysis (CSF/serum analysis), whereas routinely performed in neuroinflammatory diseases, still requires standardization to be used as an aid to the clinically based diagnosis of AD. Several AD-related CSF parameters (total tau, phosphorylated forms of tau, A beta peptides, ApoE genotype, p97, etc.) tested separately or in a combination provide sensitivity and specificity in the range of 85%, the figure commonly expected from a good diagnostic tool. In this review, recently published reports regarding progress in neurochemical pre-mortem diagnosis of dementias are discussed with a focus on an early and differential diagnosis of AD. Novel perspectives offered by recently introduced technologies, e.g, fluorescence correlation spectroscopy (FCS) and surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) are briefly discussed.
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| 6. |
- Winblad, B, et al.
(författare)
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Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment.
- 2004
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Ingår i: Journal of internal medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 256:3, s. 240-6
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Forskningsöversikt (refereegranskat)abstract
- The First Key Symposium was held in Stockholm, Sweden, 2-5 September 2003. The aim of the symposium was to integrate clinical and epidemiological perspectives on the topic of Mild Cognitive Impairment (MCI). A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics. Agreement on new perspectives, as well as recommendations for management and future research were discussed by the international working group. The specific recommendations for the general MCI criteria include the following: (i) the person is neither normal nor demented; (ii) there is evidence of cognitive deterioration shown by either objectively measured decline over time and/or subjective report of decline by self and/or informant in conjunction with objective cognitive deficits; and (iii) activities of daily living are preserved and complex instrumental functions are either intact or minimally impaired.
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| 7. |
- Zetterberg, H., et al.
(författare)
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Head trauma in sports - clinical characteristics, epidemiology and biomarkers
- 2019
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Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796. ; 285:6, s. 624-634
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Forskningsöversikt (refereegranskat)abstract
- Traumatic brain injury (TBI) is clinically divided into a spectrum of severities, with mild TBI being the least severe form and a frequent occurrence in contact sports, such as ice hockey, American football, rugby, horse riding and boxing. Mild TBI is caused by blunt nonpenetrating head trauma that causes movement of the brain and stretching and tearing of axons, with diffuse axonal injury being a central pathogenic mechanism. Mild TBI is in principle synonymous with concussion; both have similar criteria in which the most important elements are acute alteration or loss of consciousness and/or post-traumatic amnesia following head trauma and no apparent brain changes on standard neuroimaging. Symptoms in mild TBI are highly variable and there are no validated imaging or fluid biomarkers to determine whether or not a patient with a normal computerized tomography scan of the brain has neuronal damage. Mild TBI typically resolves within a few weeks but 10-15% of concussion patients develop postconcussive syndrome. Repetitive mild TBI, which is frequent in contact sports, is a risk factor for a complicated recovery process. This overview paper discusses the relationships between repetitive head impacts in contact sports, mild TBI and chronic neurological symptoms. What are these conditions, how common are they, how are they linked and can they be objectified using imaging or fluid-based biomarkers? It gives an update on the current state of research on these questions with a specific focus on clinical characteristics, epidemiology and biomarkers.
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| 8. |
- Chong, J. R., et al.
(författare)
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Blood-based high sensitivity measurements of beta-amyloid and phosphorylated tau as biomarkers of Alzheimer's disease: a focused review on recent advances
- 2021
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 92:11, s. 1231-1241
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Forskningsöversikt (refereegranskat)abstract
- Discovery and development of clinically useful biomarkers for Alzheimer's disease (AD) and related dementias have been the focus of recent research efforts. While cerebrospinal fluid and positron emission tomography or MRI-based neuroimaging markers have made the in vivo detection of AD pathology and its consequences possible, the high cost and invasiveness have limited their widespread use in the clinical setting. On the other hand, advances in potentially more accessible blood-based biomarkers had been impeded by lack of sensitivity in detecting changes in markers of the hallmarks of AD, including amyloid-beta (A beta) peptides and phosphorylated tau (P-tau). More recently, however, emerging technologies with superior sensitivity and specificity for measuring A beta and P-tau have reported high concordances with AD severity. In this focused review, we describe several emerging technologies, including immunoprecipitation-mass spectrometry (IP-MS), single molecule array and Meso Scale Discovery immunoassay platforms, and appraise the current literature arising from their use to identify plaques, tangles and other AD-associated pathology. While there is potential clinical utility in adopting these technologies, we also highlight the further studies needed to establish A beta and P-tau as blood-based biomarkers for AD, including validation with existing large sample sets, new independent cohorts from diverse backgrounds as well as population-based longitudinal studies. In conclusion, the availability of sensitive and reliable measurements of A beta peptides and P-tau species in blood holds promise for the diagnosis, prognosis and outcome assessments in clinical trials for AD.
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| 9. |
- deLeon, MJ, et al.
(författare)
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Imaging and CSF studies in the preclinical diagnosis of Alzheimer's disease
- 2007
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 1749-6632 .- 0077-8923. ; 1097, s. 114-145
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Forskningsöversikt (refereegranskat)abstract
- It is widely believed that the path to early and effective treatment for Alzheimer's disease (AD) requires the development of early diagnostic markers that are both sensitive and specific. To this aim, using longitudinal study designs, we and others have examined magnetic resonance imaging (MRI), 2-fluoro-2-deoxy-d-glucose-positron emission tomography (FDG/PET), and cerebrospinal fluid (CSF) biomarkers in cognitively normal elderly (NL) subjects and in patients with mild cognitive impairment (MCI). Such investigations have led to the often replicated findings that structural evidence of hippocampal atrophy as determined by MRI, as well as metabolic evidence from FDG-PET scan of hippocampal damage, predicts the conversion from MCI to AD. In this article we present a growing body of evidence of even earlier diagnosis. Brain pathology can be detected in NL subjects and used to predict future transition to MCI. This prediction is enabled by examinations revealing reduced glucose metabolism in the hippocampal formation (hippocampus and entorhinal cortex [EC]) as well as by the rate of medial temporal lobe atrophy as determined by MRI. However, neither regional atrophy nor glucose metabolism reductions are specific for AD. These measures provide secondary not primary evidence for AD. Consequently, we will also summarize recent efforts to improve the diagnostic specificity by combining imaging with CSF biomarkers and most recently by evaluating amyloid imaging using PET. We conclude that the combined use of conventional imaging, that is MRI or FDG-PET, with selected CSF biomarkers incrementally contributes to the early and specific diagnosis of AD. Moreover, selected combinations of imaging and CSF biomarkers measures are of importance in monitoring the course of AD and thus relevant to evaluating clinical trials.
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| 10. |
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