| 91. |
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| 92. |
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| 93. |
- Ashton, Nicholas J., et al.
(author)
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A plasma protein classifier for predicting amyloid burden for preclinical Alzheimer's disease.
- 2019
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In: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:2
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Journal article (peer-reviewed)abstract
- A blood-based assessment of preclinical disease would have huge potential in the enrichment of participants for Alzheimer's disease (AD) therapeutic trials. In this study, cognitively unimpaired individuals from the AIBL and KARVIAH cohorts were defined as Aβ negative or Aβ positive by positron emission tomography. Nontargeted proteomic analysis that incorporated peptide fractionation and high-resolution mass spectrometry quantified relative protein abundances in plasma samples from all participants. A protein classifier model was trained to predict Aβ-positive participants using feature selection and machine learning in AIBL and independently assessed in KARVIAH. A 12-feature model for predicting Aβ-positive participants was established and demonstrated high accuracy (testing area under the receiver operator characteristic curve = 0.891, sensitivity = 0.78, and specificity = 0.77). This extensive plasma proteomic study has unbiasedly highlighted putative and novel candidates for AD pathology that should be further validated with automated methodologies.
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| 94. |
- Aurora, P., et al.
(author)
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Multiple breath inert gas washout as a measure of ventilation distribution in children with cystic fibrosis
- 2004
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In: Thorax. - : BMJ. - 0040-6376. ; 59:12, s. 1068-73
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Journal article (peer-reviewed)abstract
- BACKGROUND: Multiple breath inert gas washout (MBW) has been suggested as a tool for detecting early cystic fibrosis (CF) lung disease. A study was undertaken to compare the relative sensitivity of MBW and spirometry for detecting abnormal lung function in school age children with CF and to compare MBW results obtained from healthy children in the UK with those recently reported from Sweden. METHODS: Forced expiratory volume in 1 second (FEV1) and maximal expiratory flow when 25% of forced vital capacity remains to be expired (MEF25) were compared with the lung clearance index (LCI) derived from sulphur hexafluoride MBW in 22 children with CF aged 6-16 years and in 33 healthy controls. RESULTS: LCI was higher in children with CF than in healthy controls (mean difference 5.1 (95% CI of difference 4.1 to 6.1) and FEV1 and MEF25 z-scores were lower (mean difference -2.3 (95% CI -2.9 to -1.7) and -1.8 (95% CI -2.4 to -1.3), respectively; p<0.001 for all). There was a significant negative correlation between LCI and FEV1 (r2 = 0.62) and MEF25 (r2 = 0.46). However, while normal (> or =-1.96 z-scores) FEV1 and MEF25 results were seen in 11 (50%) and 12 (53%) children with CF, respectively, all but one of these children had an abnormally increased LCI. LCI was repeatable in both groups (within subject CV for three measurements 6% for CF and 5% for healthy children). In healthy subjects LCI was independent of age and virtually identical in the British and Swedish children (mean difference 0.1 (95% CI -0.1 to 0.4), p = 0.38) CONCLUSIONS: MBW is reproducible between laboratories, generates normal ranges which are constant over childhood, and is more frequently abnormal than spirometry in children with CF.
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| 95. |
- Aurora, P., et al.
(author)
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Multiple-breath washout as a marker of lung disease in preschool children with cystic fibrosis
- 2005
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In: Am J Respir Crit Care Med. - 1073-449X. ; 171:3, s. 249-56
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Journal article (peer-reviewed)abstract
- Sensitive measures of lung function applicable to young subjects are needed to detect early cystic fibrosis (CF) lung disease. Forty children with CF aged 2 to 5 years and 37 age-matched healthy control subjects performed multiple-breath inert gas washout, plethysmography, and spirometry. Thirty children in each group successfully completed all measures, with success on first visit being between 68 and 86% for all three measures. Children with CF had significantly higher lung clearance index (mean [95% CI] difference for CF control 2.7 [1.9, 3.6], p < 0.001) and specific airway resistance (1.65 z-scores [0.96, 2.33], p < 0.001), and significantly lower forced expired volume in 0.5 seconds (-0.49 z-scores [-0.95, -0.03], p < 0.05). Abnormal lung function results were identified in 22 (73%) of 30 children with CF by multiple-breath washout, compared with 14 (47%) of 30 by plethysmography, and 4 (13%) of 30 by spirometry. Children with CF who were infected with Pseudomonas aeruginosa had significantly higher lung clearance index, but no significant difference in other lung function measures, when compared with noninfected children. Most preschool children can perform multiple-breath washout, plethysmography, and spirometry at first attempt. Multiple-breath washout detects abnormal lung function in children with CF more readily than plethysmography or spirometry.
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| 96. |
- Ayton, Scott, et al.
(author)
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Acute phase markers in CSF reveal inflammatory changes in Alzheimer's disease that intersect with pathology, APOE ε4, sex and age
- 2021
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In: Progress in Neurobiology. - : Elsevier BV. - 0301-0082. ; 198
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Journal article (peer-reviewed)abstract
- It is unknown how neuroinflammation may feature in the etiology of Alzheimer's disease (AD). We profiled acute phase response (APR) proteins (α1-antitrypsin, α1-antichymotrypsin, ceruloplasmin, complement C3, ferritin, α-fibrinogen, β-fibrinogen, γ-fibrinogen, haptoglobin, hemopexin) in CSF of 1291 subjects along the clinical and biomarker spectrum of AD to investigate the association between inflammatory changes, disease outcomes, and demographic variables. Subjects were stratified by Aβ42/t-tau as well as the following clinical diagnoses: cognitively normal (CN); subjective cognitive decline (SCD); mild cognitive impairment (MCI); and AD dementia. In separate multiple regressions (adjusting for diagnosis, age, sex, APOE-ε4) of each APR protein and a composite of all APR proteins, CSF Aβ42/t-tau status was associated with elevated ferritin, but not any other APR protein in CN and SCD subjects. Rather, the APR was elevated along with symptomatic progression (CN < SCD < MCI < AD), and this was elevation was mediated by CSF p-tau181. APOE ε4 status did not affect levels of any APR proteins in CSF, while these were elevated in males and with increased age. The performance of the APR in predicting clinical diagnosis was influenced by APOE ε4 status, sex, and age. These data provide new insight into inflammatory changes in AD and how this intersects with pathology changes and patient demographics.
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| 97. |
- Ayton, Scott, et al.
(author)
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The Neuroinflammatory Acute Phase Response in Parkinsonian-Related Disorders
- 2022
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In: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 37:5, s. 993-1003
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Journal article (peer-reviewed)abstract
- Background: Neuroinflammation is implicated in the pathophysiology of Parkinson's disease (PD) and related conditions, yet prior clinical biomarker data report mixed findings. Objectives: The aim was to measure a panel of neuroinflammatory acute phase response (APR) proteins in the cerebrospinal fluid (CSF) of participants with PD and related disorders. Methods: Eleven APR proteins were measured in the CSF of 867 participants from the BioFINDER cohort who were healthy (612) or had a diagnosis of PD (155), multiple system atrophy (MSA) (26), progressive supranuclear palsy (PSP) (22), dementia with Lewy bodies (DLB) (23), or Parkinson’s disease with dementia (PDD) (29). Results: CSF APR proteins were mostly unchanged in PD, with only haptoglobin and α1-antitrypsin significantly elevated compared to controls. These proteins were variably increased in the other disorders. Certain protein components yielded unique signatures according to diagnosis: ferritin and transthyretin were selectively elevated in MSA and discriminated these patients from all others. Haptoglobin was selectively increased in PSP, discriminating this disease from MSA when used in combination with ferritin and transthyretin. This panel of proteins did not correlate well with severity of motor impairment in any disease category, but several (particularly ceruloplasmin and ferritin) were associated with memory performance (Mini-Mental State Examination) in patients with DLB and PDD. Conclusions: These findings provide new insights into inflammatory changes in PD and related disorders while also introducing biomarkers of potential clinical diagnostic utility.
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| 98. |
- Beal, Rachel E., et al.
(author)
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Structural Origins of Light-Induced Phase Segregation in Organic-Inorganic Halide Perovskite Photovoltaic Materials
- 2020
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In: Matter. - : Elsevier BV. - 2590-2393 .- 2590-2385. ; 2:1, s. 207-219
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Journal article (peer-reviewed)abstract
- Organic-inorganic metal-halide perovskite materials offer a promising route to reducing the dollars-per-watt cost of solar energy due to their good optoelectronic properties and facile, scalable processing. Compositional tuning allows for the preparation of absorbers with band gaps tailor-made for specific tandem and single-junction applications, but photoinduced phase segregation in mixed-halide materials leads to the formation of low-band-gap regions that reduce the voltage of devices. This work explores the structural origins of photoinduced phase segregation in FA(y)Cs(1-y)Pb(BrxI1-x)(3) perovskite alloys. We use synchrotron X- ray diffraction to map the solvus between the cubic and cubic-tetragonal mixed-phase region and time-dependent photoluminescence to assess stability under illumination. We show that the correlation between crystallographic phase and phase-segregation behavior is imperfect, so phase is not the sole determinant of optical stability. Instead, we consider several possible mechanisms that could underlie the dependence of optical stability on perovskite composition.
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| 99. |
- Bornehag, Carl-Gustaf, 1957-, et al.
(author)
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Association of Prenatal Phthalate Exposure with Language Development in Early Childhood
- 2018
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In: JAMA pediatrics. - : American Medical Association. - 2168-6203 .- 2168-6211. ; 172:12, s. 1169-1176
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Journal article (peer-reviewed)abstract
- Importance: Prenatal exposure to phthalates has been associated with neurodevelopmental outcomes, but little is known about the association with language development. Objective: To examine the association of prenatal phthalate exposure with language development in children in 2 population-based pregnancy cohort studies. Design, Setting, and Participants: Data for this study were obtained from the Swedish Environmental Longitudinal Mother and Child, Asthma and Allergy (SELMA) study conducted in prenatal clinics throughout Värmland county in Sweden and The Infant Development and the Environment Study (TIDES) conducted in 4 academic centers in the United States. Participants recruited into both studies were women in their first trimester of pregnancy who had literacy in Swedish (SELMA) or English or Spanish (TIDES). This study included mothers and their children from both the SELMA study (n = 963) and TIDES (n = 370) who had complete data on prenatal urinary phthalate metabolite levels, language delay, and modeled covariables. For SELMA, the data were collected from November 1, 2007, to June 30, 2013, and data analysis was conducted from November 1, 2016, to June 30, 2018. For TIDES, data collection began January 1, 2010, and ended March 29, 2016, and data analysis was performed from September 15, 2016, to June 30, 2018. Main Outcomes and Measures: Mothers completed a language development questionnaire that asked the number of words their children could understand or use at a median of 30 months of age (SELMA) and 37 months of age (TIDES). The responses were categorized as fewer than 25, 25 to 50, and more than 50 words, with 50 words or fewer classified as language delay. Results: In the SELMA study, 963 mothers, 455 (47.2%) girls, and 508 [52.8%] boys were included. In TIDES, 370 mothers, 185 (50.0%) girls, and 185 (50.0%) boys were included in this analysis. The prevalence of language delay was 10.0% in both SELMA (96 reported) and TIDES (37 reported), with higher rates of delay in boys than girls (SELMA: 69 [13.5%] vs 27 [6.0%]; TIDES: 12 [12.4%] vs 14 [7.6%]). In crude analyses, the metabolite levels of dibutyl phthalate and butyl benzyl phthalate were statistically significantly associated with language delay in both cohorts. In adjusted analyses, a doubling of prenatal exposure of dibutyl phthalate and butyl benzyl phthalate metabolites increased the odds ratio (OR) for language delay by approximately 25% to 40%, with statistically significant results in the SELMA study (dibutyl phthalate OR, 1.29 [95% CI, 1.03-1.63; P =.03]; butyl benzyl phthalate OR, 1.26 [95% CI, 1.07-1.49; P =.003]). A doubling of prenatal monoethyl phthalate exposure was associated with an approximately 15% increase in the OR for language delay in the SELMA study (OR, 1.14; 95% CI, 1.00-1.31; P =.05), but no such association was found in TIDES (OR, 0.98; 95% CI, 0.79-1.23). Conclusions and Relevance: In findings from this study, prenatal exposure to dibutyl phthalate and butyl benzyl phthalate was statistically significantly associated with language delay in children in both the SELMA study and TIDES. These findings, along with the prevalence of prenatal exposure to phthalates, the importance of language development, and the inconsistent results from a 2017 Danish study, suggest that the association of phthalates with language delay may warrant further examination.
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| 100. |
- Brand, Paul L P, et al.
(author)
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Classification and pharmacological treatment of preschool wheezing: changes since 2008.
- 2014
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 43:4, s. 1172-1177
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Journal article (peer-reviewed)abstract
- Since the publication of the European Respiratory Society Task Force report in 2008, significant new evidence has become available on the classification and management of preschool wheezing disorders. In this report, an international consensus group reviews this new evidence and proposes some modifications to the recommendations made in 2008. Specifically, the consensus group acknowledges that wheeze patterns in young children vary over time and with treatment, rendering the distinction between episodic viral wheeze and multiple-trigger wheeze unclear in many patients. Inhaled corticosteroids remain first-line treatment for multiple-trigger wheeze, but may also be considered in patients with episodic viral wheeze with frequent or severe episodes, or when the clinician suspects that interval symptoms are being under reported. Any controller therapy should be viewed as a treatment trial, with scheduled close follow-up to monitor treatment effect. The group recommends discontinuing treatment if there is no benefit and taking favourable natural history into account when making decisions about long-term therapy. Oral corticosteroids are not indicated in mild-to-moderate acute wheeze episodes and should be reserved for severe exacerbations in hospitalised patients. Future research should focus on better clinical and genetic markers, as well as biomarkers, of disease severity.
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