Background: EMBRACE (NCT02462759) Part 1 is a randomized, double-blind, sham-procedure controlled study assessing safety/tolerability of intrathecal nusinersen (12-mg equivalent dose) in symptomatic infants/children with SMA who were not eligible to participate in ENDEAR or CHERISH. Methods: Eligible participants had onset of SMA symptoms at ≤6 months with 3 SMN2 copies; onset at ≤6 months, age >7 months and 2 copies; or onset at >6 months, age ≤18 months, and 2/3 copies. Safety/tolerability was the primary endpoint. Exploratory endpoints included Hammersmith Infant Neurological Examination Section 2 (HINE-2) motor milestone attainment, change in ventilator use, and growth. Results: EMBRACE Part 1 was terminated early based on positive results from ENDEAR. Safety/tolerability was similar to previous trials. More nusinersen-treated (11/14;79%) vs. sham–treated individuals (2/7;29%) were HINE-2 motor milestone responders. Between Day 183 and 302, mean (SD) hours of ventilator use changed by +1.236 (3.712) hours in nusinersen-treated (n=12) and +2.123 (3.023) hours in sham–treated individuals (n=7). Similar increases in weight and body length were observed in nusinersen-treated and sham–treated individuals by Day 183. Conclusions: In EMBRACE Part 1, nusinersen demonstrated a favorable benefit-risk profile. These results add to the aggregated efficacy, safety/tolerability data of nusinersen in SMA.

Study Supported by: Ionis and Biogen

This study aimed to compare the quality of beef from suckler bulls raised on a high-energy concentrate ration and slaughtered at different carcass weights (CW)/ages. In total, 42 spring-born, Charolais and Limousin-sired, weaned suckler bulls were provided with a finishing diet of ad libitum concentrates and grass silage until they reached target CW of 340, 380 and 420 kg. Intramuscular fat (IMF) content tended (P<0.06) to be higher for 420 kg CW than for 380 and 340 kg CW. Sensory tenderness was lower (P<0.001) for 420 kg CW than for 380 and 340 kg CW. Juiciness was higher (P<0.05) for 420 kg CW than for 380 kg CW. Flavour liking was higher (P<0.05) for 420 and 380 kg CW (which did not differ) than for 340 kg CW. Overall, an increase in CW resulted in a slight increase in IMF content which could be responsible for the increase in juiciness and flavour liking of the beef. An increase in CW led to a decrease in the tenderness of the beef even though the overall liking of the beef was not affected.

Research has shown both production and health benefits for the use of chicory (Cichorium intybus) within ruminant diets. Despite this, little was known about the effects of this forage, containing differing fatty acid profiles and secondary plant compounds compared with ryegrass, on beef stability, fatty acid composition or sensory properties. An experiment was conducted to investigate whether the inclusion of chicory in the diet of grazing beef steers would alter these three properties in the M. Longissimus muscle when compared with beef steers grazing perennial ryegrass (Lolium perenne). Triplicate 2 ha plots were established with a chicory (cv. Puna II)/perennial ryegrass mix or a perennial ryegrass control. A core group of 36 Belgian Blue – cross steers were used within a 2-year beef finishing experiment (n=6/replicate plot). In the 2nd grazing year, steers were slaughtered as they reached a target fat class of 3. Muscle pH was checked 2 and 48 h post-slaughter. A section of the hindloin joint containing the M. Longissimus lumborum muscle was removed and a 20 mm-thick steak was cut and muscle samples were taken for analysis of vitamin E and fatty acid analysis. The remaining section of the loin was vacuum packed in modified atmosphere packs and subjected to simulated retail display. A section of the conditioned loin was used for sensory analysis. Data on pH, vitamin E concentration and colour stability in a simulated retail display showed there were no effects of including chicory in the diet of grazing beef steers on meat stability. There were also no differences found in the fatty acid composition or the overall eating quality of the steaks from the two treatments. In conclusion, there were no substantive effects of including chicory in the swards of grazing beef cattle on meat stability, fatty acid composition or sensory properties of the M. Longissimus muscle when compared with beef steers grazing ryegrass-only swards.

In grass-based beef production systems (PS), early maturing (EM) breed types may be preferable to late maturing (LM) breed types in achieving adequate carcass fat cover. Biochemical and organoleptic characteristics of muscle from suckler bulls were investigated in EM and LM (n=28/breed) assigned to one of two PS (ad libitum concentrates and grass silage to slaughter (C) or ad libitum silage plus 2 kg concentrate daily during winter followed by 99 days at pasture and then an indoor finishing period on C (GSPC)) in a 2 breed type×2 PS factorial arrangement of treatments. Bulls were managed to have a common target carcass weight of 380 kg. Intramuscular fat (IMF) content was higher (P<0.05) for EM than LM, and for C than GSPC bulls. Collagen solubility was higher (P<0.05) for C than GSPC bulls. Lactate dehydrogenase (LDH) and phosphofructokinase activities were higher (P<0.05) for LM than EM. Isocitrate dehydrogenase activity and the Type I myosin heavy chain (MyHC) proportion were higher (P<0.05) for EM than LM. The LDH activity and the Type IIX MyHC proportion were higher (P<0.05) for C than GSPC bulls. Sensory ratings for tenderness and juiciness were higher (P<0.01) for beef from EM than LM while sensory ratings for tenderness, flavour liking and overall liking were higher (P<0.001) for C than for GSPC bulls. Differences in sensory quality were largely eliminated when adjusted for IMF. Overall, carcass fat scores, IMF and sensory scores were higher in EM than LM and in C than GSPC bulls but most differences in sensory quality could be attributed to differences in IMF.

Eta Carinae is one of the most massive observable binaries. Yet determination of its orbital and physical parameters is hampered by obscuring winds. However the effects of the strong, colliding winds changes with phase due to the high orbital eccentricity. We wanted to improve measures of the orbital parameters and to determine the mechanisms that produce the relatively brief, phase-locked minimum as detected throughout the electromagnetic spectrum. We conducted intense monitoring of the He ii λ4686 line in η Carinae for 10 months in the year 2014, gathering ~300 high S/N spectra with ground- and space-based telescopes. We also used published spectra at the FOS4 SE polar region of the Homunculus, which views the minimum from a different direction. We used a model in which the He ii λ4686 emission is produced by two mechanisms: a) one linked to the intensity of the wind-wind collision which occurs along the whole orbit and is proportional to the inverse square of the separation between the companion stars; and b) the other produced by the ‘bore hole’ effect which occurs at phases across the periastron passage. The opacity (computed from 3D SPH simulations) as convolved with the emission reproduces the behavior of equivalent widths both for direct and reflected light. Our main results are: a) a demonstration that the He ii λ4686 light curve is exquisitely repeatable from cycle to cycle, contrary to previous claims for large changes; b) an accurate determination of the longitude of periastron, indicating that the secondary star is ‘behind’ the primary at periastron, a dispute extended over the past decade; c) a determination of the time of periastron passage, at ~4 days after the onset of the deep light curve minimum; and d) show that the minimum is simultaneous for observers at different lines of sight, indicating that it is not caused by an eclipse of the secondary star, but rather by the immersion of the wind-wind collision interior to the inner wind of the primary.

Bull beef production is traditionally based on high concentrate rations fed indoors. Inclusion of grazed grass, which is generally a cheaper feed, would decrease the cost of bull beef production, but may affect beef quality. Accordingly, the organoleptic quality and composition of beef from continental-sired suckler bulls (n=126) assigned to either ad libitum concentrates to slaughter (C), grass silage (GS) ad libitum for 120 days followed by C (GSC) or GS followed by 100 days at pasture and then C (GSPC) and slaughtered at target carcass weights (CW) of 360, 410 or 460 kg was examined. Tenderness, flavour liking and overall liking were lower (P<0.05) for GSPC than for C and GSC. Intramuscular fat content and soluble collagen proportion were lower (P<0.05) for GSPC than GSC which was lower (P<0.05) than C. Soluble collagen proportion was lower (P<0.05) for 460 kg than 410 kg CW, which was lower (P<0.05) than 360 kg CW. Inclusion of a grazing period decreased the ratings of tenderness, flavour liking and overall liking, but age of the bulls at slaughter had no clear influence on sensory characteristics.

We sought to explain seasonality and other aspects of Campylobacter jejuni epidemiology by integrating population genetic and epidemiological analysis in a large 3-year longitudinal, two-centre, population-based study. Epidemiological information was collected for 1505 isolates, which were multilocus sequence-typed. Analyses compared pathogen population structure between areas, over time, and between clinical presentations. Pooled analysis was performed with published international datasets. Subtype association with virulence was not observed. UK sites had nearly identical C. jejuni populations. A clade formed by ST45 and ST283 clonal complexes showed a summer peak. This clade was common in a Finnish dataset but not in New Zealand and Australian collections, countries with less marked seasonality. The UK, New Zealand and Australian collections were otherwise similar. These findings map to known in-vitro differences of this clade. This identifies a target for studies to elucidate the drivers of the summer peak in human C. jejuni infection.

The objective of this study was to examine the online use of near infrared reflectance (NIR) spectroscopy to estimate the concentration of individual and groups of fatty acids (FA) as well as intramuscular fat (IMF) in crossbred Aberdeen Angus (AA×) and Limousin (LIM×) cattle. This was achieved by direct application of a fibre-optic probe to the muscle immediately after exposing the meat surface in the abattoir at 48 h post mortem. Samples of M. longissimus thoracis from 88 AA× and 106 LIM× were scanned over the NIR spectral range from 350 to 1800 nm and samples of the M. longissimus lumborum were analysed for IMF content and FA composition. Statistically significant differences (P < 0.001) were observed in most FA between the two breeds studied, with FA concentration being higher in AA× meat mainly. NIR calibrations, tested by cross-validation, showed moderate to high predictability in LIM× meat samples for C16:0, C16:1, C18:0, trans11 C18:1, C18:1, C18:2 n-6, C20:1, cis9, trans11 C18:2, SFA (saturated FA), MUFA (monounsaturated FA), PUFA (polyunsaturated FA) and IMF content with R2 (SECV, mg/100 g muscle) of 0.69 (146), 0.69 (28), 0.71 (62), 0.70 (8.1), 0.76 (192), 0.65 (13), 0.71 (0.9), 0.71 (2.9), 0.68 (235), 0.75 (240), 0.64 (17) and 0.75 (477), respectively. FA such as C14:0, C18:3 n-3, C20:4 n-6, C20:5 n-3, C22:6 n-3, n-6 and n-3 were more difficult to predict by NIR in these LIM× samples (R2 = 0.12 to 0.62; SECV = 0.5 to 26 mg/100 g muscle). In contrast, NIR showed low predictability for FA in AA× beef samples. In particular for LIM×, the correlations of NIR measurements and several FA in the range from 0.81 to 0.87 indicated that the NIR spectroscopy is a useful online technique for the early, fast and relatively inexpensive estimation of FA composition in the abattoir.

The potential of the composition of the forerib measured by X-ray computed tomography (CT) as a predictor of carcass composition was evaluated using data recorded on 30 Aberdeen Angus and 43 Limousin crossbred heifers and steers. The left sides of the carcasses were split into 20 cuts, which were CT scanned and fully dissected into fat, muscle and bone. Carcass and forerib tissue weights were assessed by dissection and CT. Carcass composition was assessed very accurately by CT scanning of the primal cuts (adj-R2 = 0.97 for the three tissues). CT scanning predicted weights of fat, muscle and bone of the forerib with adj-R2 of 0.95, 0.91 and 0.75, respectively. Single regression models with the weights of fat, muscle or bone in the forerib measured by CT as the only predictors to estimate fat, muscle or bone of the left carcass obtained by CT showed adjusted coefficients of determination (adj-R2) of 0.79, 0.60 and 0.52, respectively. By additionally fitting breed and sex, accuracy increased to 0.85, 0.73 and 0.67. Using carcass and forerib weights in addition to the previous predictors improved significantly the prediction accuracy of carcass fat and muscle weights to adj-R2 values of 0.92 and 0.96, respectively, while the highest value for carcass bone weight was 0.77. In general, equations derived using CT data had lower adj-R2 values for bone, but better accuracies for fat and muscle compared to those obtained using dissection. CT scanning could be considered as an alternative very accurate and fast method to assess beef carcass composition that could be very useful for breeding programmes and research studies involving a large number of animals, including the calibration of other indirect methods (e.g. in vivo and carcass video image analysis).

Following a case of Legionnaires' disease Legionella pneumophila of the same serogroup was isolated from the hot water system of the hotel which had been epidemiologically implicated as the source of the infection. Pyrolysis mass spectrometry (PyMS) was used to compare 11 isolates from the hotel water sample with the patient's strain. Epidemiologically unrelated isolates, both clinical and environmental, of the same serogroup and monoclonal antibody type of L. pneumophila were included in the same analysis, together with relevant reference strains. The patient strain was shown to be indistinguishable from seven of the hotel water isolates, but clearly different from other unrelated clinical isolates, the reference strains and some of the other environmental isolates. PyMS is a rapid and cheap method for inter-strain comparison for L. pneumophila.

Meat tenderness is the single most important quality attribute in consumer acceptance studies of meat eating quality. Several mechanical-based techniques have been developed to provide an objective measure of meat tenderness that have good correlation with sensory tenderness, as assessed by trained taste panel. The classic Warner-Bratzler shear force technique (WBSF) has shown correlations with sensory tenderness in the range of -0.39 to -0.77 (Van Oeckel et al., 1999; Shackelford et al., 1999a), whilst the Volodkevitch bite test attempts to imitate the incisor biting action by a compression method. A rapid slice shear force (SSF) test, which uses only one steak and hot meat (significant benefits in a commercial environment), had a stronger correlation with taste panel tenderness scores than WBSF (Shackelford et al., 1999b). The Meat Industry Research Institute of New Zealand (MIRINZ) test results, transformed into categories, was highly correlated (-0.97) with sensory tenderness (Bickerstaffe et al., 2001). The objective of this study was to evaluate the associations between objective physical measures (SSF, MIRINZ and Volodkevitch) and taste panel tenderness scores in beef.

The standard instrumental method for measurement of texture, Warner Bratzler shear force (WBSF), involves shearing six ‘good’ cores taken from a cooked sample of meat, with coring parallel to the fibre direction (AMSA, 1995), which is a time consuming and destructive methodology. A new, more rapid method, the slice shear force (SSF) test was developed which involves measuring the shear force of a single slice per sample (Shackelford et al 1999a). Shackelford et al. (1999b) reported that SSF was strongly correlated with sensory scores for 14d aged meat. The aim of the current investigation was to study the effect of sex differences on instrumental meat quality and to identify the relationship between SSF measured at 2 days and WBSF values measured at 14 and 21 days post slaughter.