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- Bartlett, Jonathan W, et al.
(författare)
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Determining cut-points for Alzheimer's disease biomarkers: statistical issues, methods and challenges.
- 2012
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Ingår i: Biomarkers in medicine. - : Future Medicine Ltd. - 1752-0371 .- 1752-0363. ; 6:4, s. 391-400
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Tidskriftsartikel (refereegranskat)abstract
- New proposed criteria for the clinical diagnosis of Alzheimer's disease increasingly incorporate biomarkers, most of which are normally measured on a continuous scale. Operationalizing such criteria thus requires continuous biomarkers to be dichotomized, which in turns requires the selection of a cut-point at which to dichotomize. In this article, we review the statistical principles underlying the choice of cut-points, describe some of the most commonly adopted statistical approaches used to estimate cut-points, highlight potential pitfalls in some of the approaches and characterize in what sense the estimated cut-point from each approach is optimal. We also emphasize that how a cut-point is selected must be made in reference to how the resulting dichotomized biomarker is to be used, and in particular what actions will follow from a positive or negative test result.
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| 2. |
- Mattsson, Jonathan, et al.
(författare)
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Normalization of Wastewater Quality to Estimate Infiltration/Inflow and Mass Flows of Metals
- 2016
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Ingår i: Journal of environmental engineering. - 0733-9372 .- 1943-7870. ; 142:11
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Tidskriftsartikel (refereegranskat)abstract
- The quality of wastewater varies between catchments due to variation in urbanisation, sewer system properties, and pollution levels. This study was conducted to identify wastewater quality parameters that could be normalized to estimate levels of infiltration/inflow (I/I) in selected catchments and to investigate the geographic origins of metals entering sewer systems. Two sampling campaigns were conducted in the five catchments of the Gothenburg area focusing on 14 water quality parameters. Data from a reference study on domestic wastewater quality to normalize the mass flows associated with pure domestic wastewater was applied. The level of dilution due to I/I in wastewater entering Rya Wastewater Treatment Plant, estimated using Tot-N and Tot-P as indicators, provided the closest fit among the water quality parameters with results obtained by established methods for the two campaigns. The results from the study also indicated which catchments generated nondomestic wastewater with higher mass flows of specified metals.
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| 3. |
- Skillbäck, Tobias, et al.
(författare)
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CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival.
- 2014
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Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 83:21, s. 1945-53
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Tidskriftsartikel (refereegranskat)abstract
- We hypothesized that CSF neurofilament light (NFL) levels would be elevated in dementias with subcortical involvement, including vascular dementia (VaD), but less elevated in dementias primarily affecting gray matter structures, such as Alzheimer disease (AD), and that elevated CSF NFL would correlate with disease severity and shorter survival time irrespective of clinical diagnosis.
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| 8. |
- Baliakas, Panagiotis, 1977-, et al.
(författare)
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Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia
- 2019
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 104:2, s. 360-369
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinico-biological differences. Considering this, we assessed prognosis separately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet A M-CLL patients, besides TP53 abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to-first-treatment and a treatment probability at five and ten years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively. Within Binet A U-CLL patients, besides TP53 abnormalities, del(11q) and/or SF3B1 mutations were associated with the shortest time-to-first-treatment (5- and 10-year treatment probability: 78% and 98%, respectively); in the remaining cases, males had a significantly worse prognosis than females. In conclusion, the relative weight of indicators that can accurately risk stratify early-stage CLL patients differs depending on the somatic hypermutation status of the immunoglobulin heavy variable genes of each patient. This finding highlights the fact that compartmentalized approaches based on immunogenetic features are necessary to refine and tailor prognostication in CLL.
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| 9. |
- 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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