Browsing by Subject "PANEL"

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  • Hayes, A.; Nguyen, D.; Andersson, M.; Anton, A.; Bailly, J-L; Beard, S.; Benschop, K. S. M.; Berginc, N.; Blomqvist, S.; Cunningham, E.; Davis, D.; Dembinski, J. L.; Diedrich, S.; Dudman, S. G.; Dyrdak, R.; Eltringham, G. J. A.; Gonzales-Goggia, S.; Gunson, R.; Howson-Wells, H. C.; Jääskeläinen, A. J.; Lopez-Labrador, F. X.; Maier, M.; Majumdar, M.; Midgley, S.; Mirand, A.; Morley, U.; Nordbo, S. A.; Oikarinen, S.; Osman, H.; Papa, A.; Pellegrinelli, L.; Piralla, A.; Rabella, N.; Richter, J.; Smith, M.; Strand, A. Söderlund; Templeton, K.; Vipond, B.; Vuorinen, T.; Williams, C.; Wollants, E.; Zakikhany, K.; Fischer, T. K.; Harvala, H.; Simmonds, P. (2020)
    Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in-house diagnostic and typing assays. Accurately quantified RNA transcript controls were distributed to 27 diagnostic and 12 reference laboratories in 17 European countries for blinded testing. Transcripts represented the four human EV species (EV-A71, echovirus 30, coxsackie A virus 21, and EV-D68), HPeV3, and specificity controls. Reported results from 48 in-house and 15 commercial assays showed 98% detection frequencies of high copy (1000 RNA copies/5 mu L) transcripts. In-house assays showed significantly greater detection frequencies of the low copy (10 copies/5 mu L) EV and HPeV transcripts (81% and 86%, respectively) compared with commercial assays (56%, 50%; P = 7 x 10(-5)). EV-specific PCRs showed low cross-reactivity with human rhinovirus C (3 of 42 tests) and infrequent positivity in the negative control (2 of 63 tests). Most or all high copy EV and HPeV controls were successfully typed (88%, 100%) by reference laboratories, but showed reduced effectiveness for low copy controls (41%, 67%). Stabilized RNA transcripts provide an effective, logistically simple and inexpensive reagent for evaluation of diagnostic assay performance. The study provides reassurance of the performance of the many in-house assay formats used across Europe. However, it identified often substantially reduced sensitivities of commercial assays often used as point-of-care tests.
  • Manousaki, Despoina; Kampe, Anders; Forgetta, Vincenzo; Makitie, Riikka E.; Bardai, Ghalib; Belisle, Alexandre; Li, Rui; Andersson, Sture; Makitie, Outi; Rauch, Frank; Richards, J. Brent (2020)
    Extreme presentations of common disease in children are often presumed to be of Mendelian etiology, but their polygenic basis has not been fully explored. We tested whether children with significant fracture history and no osteogenesis imperfecta (OI) are at increased polygenic risk for fracture. A childhood significant fracture history was defined as the presence of low-trauma vertebral fractures or multiple long bone fractures. We generated a polygenic score of heel ultrasound-derived speed of sound, termed "gSOS," which predicts risk of osteoporotic fracture. We tested if individuals from three cohorts with significant childhood fracture history had lower gSOS. A Canadian cohort included 94 children with suspected Mendelian osteoporosis, of which 68 had negative OI gene panel. Two Finnish cohorts included 59 children with significant fracture history and 22 with suspected Mendelian osteoporosis, among which 18 had no OI. After excluding individuals with OI and ancestral outliers, we generated gSOS estimates and compared their mean to that of a UK Biobank subset, representing the general population. The average gSOS across all three cohorts (n = 131) was -0.47 SD lower than that in UK Biobank (n = 80,027, p = 1.1 x 10(-5)). The gSOS of 78 individuals with suspected Mendelian osteoporosis was even lower (-0.76 SD, p = 5.3 x 10(-10)). Among the 131 individuals with a significant fracture history, we observed 8 individuals with gSOS below minus 2 SD from the mean; their mean lumbar spine DXA-derived bone mineral density Z-score was -1.7 (SD 0.8). In summary, children with significant fracture history but no OI have an increased burden of common risk alleles. This suggests that a polygenic contribution to disease should be considered in children with extreme presentations of fracture. (c) 2020 American Society for Bone and Mineral Research.
  • Lahelma, Eero; Pietiläinen, Olli; Chandola, Tarani; Hyde, Martin; Rahkonen, Ossi; Lallukka, Tea (2019)
    Background Prior analyses of class differences in health trajectories among employees have often omitted women and transitions to retirement. We examined social class trajectories in physical functioning among Finnish female employees from midlife to retirement age, and whether transitions to retirement modified these trajectories. Methods Data were derived from mail surveys at Phases 1-3 (2000-2012) among employees of the City of Helsinki, Finland, aged 40-60 at baseline (n = 8960, 80% women, response rates 69-83%). We included respondents to any of the Phases 1-3 aged 40-72 (n = 6976). We distinguished higher and lower social classes, and employment statuses, i.e. employed, mandatorily retired and disability-retired. Short Form 36 physical component summary was used to measure physical functioning. Mixed-effect growth curve models were used to assess the association of social class and employment status with functioning over age. Results For employed women, physical functioning deteriorated faster in the lower than in the higher class, with class trajectories widening in ages 40-65. After mandatory retirement, functioning deteriorated in both classes, whereas after disability retirement, functioning improved. Across employment statuses, functioning converged at older ages, and the disability-retired caught up with the better functioning of the employed and mandatorily retired. Employment status modified the trajectories, as among the continuously employed and mandatorily retired women functioning deteriorated, but among the disability-retired, trajectories improved and reached a similar level with employed and mandatorily retired women. Social class inequalities remained in all employment status groups. Conclusions Overall, our results suggest evidence for the cumulative disadvantage model, with accumulating work exposures among lower classes potentially contributing to their trajectories of ill health.