Clinical implications of serum neurofilament in newly diagnosed MS patients: a longitudinal multicentre cohort study

BACKGROUND: We aim to evaluate serum neurofilament light chain (sNfL), indicating neuroaxonal damage, as a biomarker at diagnosis in a large cohort of early multiple sclerosis (MS) patients. METHODS: In a multicentre prospective longitudinal observational cohort, patients with newly diagnosed relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS) were recruited between August 2010 and November 2015 in 22 centers. Clinical parameters, MRI, and sNfL levels (measured by single molecule array) were assessed at baseline and up to four-year follow-up. FINDINGS: Of 814 patients, 54.7% (445) were diagnosed with RRMS and 45.3% (369) with CIS when applying 2010 McDonald criteria (RRMS[2010] and CIS[2010]). After reclassification of CIS[2010] patients with existing CSF analysis, according to 2017 criteria, sNfL levels were lower in CIS[2017] than RRMS[2017] patients (9.1 pg/ml, IQR 6.2-13.7 pg/ml, n = 45; 10.8 pg/ml, IQR 7.4-20.1 pg/ml, n = 213; p = 0.036). sNfL levels correlated with number of T2 and Gd+ lesions at baseline and future clinical relapses. Patients receiving disease-modifying therapy (DMT) during the first four years had higher baseline sNfL levels than DMT-naïve patients (11.8 pg/ml, IQR 7.5-20.7 pg/ml, n = 726; 9.7 pg/ml, IQR 6.4-15.3 pg/ml, n = 88). Therapy escalation decisions within this period were reflected by longitudinal changes in sNfL levels. INTERPRETATION: Assessment of sNfL increases diagnostic accuracy, is associated with disease course prognosis and may, particularly when measured longitudinally, facilitate therapeutic decisions

Development of genetic models for estimation of racing performances in German thoroughbreds

Abstract. The objective of this study was to develop new statistical models for genetic estimation of racing performances in German thoroughbreds. Analysed performance traits were "square root of rank at finish", "square root of distance to first placed horse in a race" and "log of earnings". These traits were found to be influenced by the carried weight, which was determined by the horse's earlier performance. Therefore, new traits were developed based on random regression models, which were independent from the carried weights. Heritabilities were first estimated for these created traits "new rank at finish" (h2 = 0.101) and "new distance to first placed horse in a race" (h2 = 0.142) by using two univariate animal models. When considering a linear regression of carried weights as fixed effect in the statistical model, heritabilities for "square root of rank at finish" (h2 = 0.086) and "square root of distance to first placed horse in a race" (h2 = 0.124) decreased. Breeding values of “new rank at finish” and "new distance to first placed horse in a race" were compared with breeding values of "square root of rank at finish" and "square root of distance to first placed horse in a race", in which carried weight was considered as fixed regression in the model. These two different models were compared by two criteria. Breeding values were overestimated for low performing thoroughbreds and underestimated for high performing horses when considering a linear regression of carried weights as fixed effect in the model. Statistical models considering new created traits ("new rank at finish" and "new distance to first placed horse in a race") which were independent of carried weights, showed better suitability for genetic estimation. Due to high genetic correlation with other traits and showing highest genetic variance a univariate animal model for the trait “new distance to first placed horse in a race” was recommended for genetic estimation. </jats:p

Quantitative trait loci identified for resistance to Stagonospora Glume Blotch in wheat in the USA and Australia

Resistance to stagonospora nodorum blotch (SNB) in glumes of hexaploid wheat (Triticum aestivum L.), caused by Phaeosphaeria (Stagonospora anamorph) nodorum was investigated in a recombinant-inbred (RI) population. The Purdue University winter wheat breeding lines P91193D1 and P92201D5, unrelated by parentage but both exhibiting partial SNB resistance, were crossed to develop 254 RI lines by single-seed descent (SSD) from a random population of F2 plants, to identify quantitative trait loci (QTLs) controlling SNB resistance in wheat glumes. The RI population, together with parent lines, was phenotyped for glume resistance to SNB under field conditions in F8:10 at Evansville, Vincennes, and Lafayette, IN, in 2003; in F7:9 at South Perth, Australia, in 2004; and in F8:10 in greenhouse-grown inoculated tests at Lafayette in 2003 and 2004. Two QTLs for resistance to SNB in glumes were identified: QSng.pur-2DL.1 from P91193D1 and QSng.pur-2DL.2 from P92201D5. The QTL QSng.pur-2DL.1 explained from 12.3% of the phenotypic variation for resistance in southern Indiana (Evansville and Vincennes) to 38.1% at South Perth; QSng.pur-2DL.2 accounted for 6.9 and 11.2% of the phenotypic variation in Indiana and South Perth, respectively. This study is the first report of SNB glume blotch resistance in which the same QTLs were identified in tests on different continents where Stagonospora nodorum populations are probably genetically diverse