Carcass Traits and M. Longissimus Lumborum Palatability Attributes of Calf- and Yearling-Finished Steers

A 2-yr experiment was conducted to compare carcass characteristics and meat palatability attributes of steers (³⁄₄ British, ¹⁄₄ Continental) finished postweaning as calves or yearlings. Calves and yearlings of the same contemporary group were designated to a finishing system at weaning. Calves (n = 73) were finished in the feedlot (191 d) on a high-concentrate diet. Yearlings (n = 84) grazed crop residues after weaning, followed by spring and summer pasture grazing, and concluded with a short finishing period (91 d) in the feedlot. All steers were fed to a constant, fat thickness endpoint of 1 cm. The M. longissimus lumborum steaks from each production system were aged for 7, 14, or 21 d for Warner-Bratzler shear force determination and for 7 or 14 d for in-house sensory panel evaluation. Insoluble, percent soluble, and total collagen were determined. Yearlings produced heavier (P \u3c 0.001) carcasses with larger (P \u3c 0.001) LM areas and lower (P \u3c 0.001) marbling scores and quality grades. Calves possessed greater amounts of total collagen (P \u3c 0.001), with a significantly greater percentage of soluble collagen compared with yearlings (39.72 vs. 24.38%). Calves produced steaks with lower (P \u3c 0.001) shear force values and greater (P \u3c 0.001) sensory ratings for flavor. The USDA Choice steaks from the calves were more (P \u3c 0.001) tender and more (P \u3c 0.050) palatable than Choice steaks from yearlings, and USDA Select steaks from calves were rated more tender (P \u3c 0.001), juicy (P = 0.012), and desirable (P \u3c 0.001) than Select steaks from yearlings. As expected, increasing aging time from 7- to 14- to 21-d produced steaks with lower (P \u3c 0.001) shear force values, regardless of the production system. Risk probabilities showed 1.24% of the steaks from calf finished steers and 21.22% of steaks from yearling-finished steers to be tough. Sensory rating probabilities showed the steaks from the calves were most likely to be desirable for tenderness, whereas steaks from the yearlings were most likely to be undesirable for tenderness, juiciness, flavor, and overall acceptability. Thus, calf-finished steers produce carcasses superior in quality and palatability compared with those from yearling finished steers. However, yearling-finished steers can produce tender beef with extended aging

Steps Toward Determination of the Size and Structure of the Broad-Line Region in Active Galactic Nuclei. XVI. A Thirteen-Year Study of Spectral Variability in NGC 5548

We present the final installment of an intensive 13-year study of variations of the optical continuum and broad H-beta emission line in the Seyfert 1 galaxy NGC 5548. The data base consists of 1530 optical continuum measurements and 1248 H-beta measurements. The H-beta variations follow the continuum variations closely, with a typical time delay of about 20 days. However, a year-by-year analysis shows that the magnitude of emission-line time delay is correlated with the mean continuum flux. We argue that the data are consistent with the simple model prediction that the size of the broad-line region is proportional to the square root of the ionizing luminosity. Moreover, the apparently linear nature of the correlation between the H-beta response time and the nonstellar optical continuum arises as a consequence of the changing shape of the continuum as it varies, specifically with the optical (5100 A) continuum luminosity proportional to the ultraviolet (1350 A) continuum luminosity to the 0.56 power.Comment: 20 pages plus 4 figures. Accepted for publication in The Astrophysical Journa

Biodistribution of intravitreal lenadogene nolparvovec gene therapy in nonhuman primates

Lenadogene nolparvovec (Lumevoq) gene therapy was developed to treat Leber hereditary optic neuropathy (LHON) caused by the m.11778G > A in MT-ND4 that affects complex I of the mitochondrial respiratory chain. Lenadogene nolparvovec is a replication-defective, single-stranded DNA recombinant adeno-associated virus vector 2 serotype 2, containing a codon-optimized complementary DNA encoding the human wild-type MT-ND4 subunit protein. Lenadogene nolparvovec was administered by unilateral intravitreal injection in MT-ND4 LHON patients in two randomized, double-masked, and sham-controlled phase III clinical trials (REVERSE and RESCUE), resulting in bilateral improvement of visual acuity. These and other earlier results suggest that lenadogene nolparvovec may travel from the treated to the untreated eye. To investigate this possibility further, lenadogene nolparvovec was unilaterally injected into the vitreous body of the right eye of healthy, nonhuman primates. Viral vector DNA was quantifiable in all eye and optic nerve tissues of the injected eye and was detected at lower levels in some tissues of the contralateral, noninjected eye, and optic projections, at 3 and 6 months after injection. The results suggest that lenadogene nolparvovec transfers from the injected to the noninjected eye, thus providing a potential explanation for the bilateral improvement of visual function observed in the LHON patients

Absence of lenadogene nolparvovec DNA in a brain tumor biopsy from a patient in the REVERSE clinical study, a case report

Background: Leber Hereditary Optic Neuropathy (LHON) is a rare, maternally-inherited mitochondrial disease that primarily affects retinal ganglion cells (RGCs) and their axons in the optic nerve, leading to irreversible, bilateral severe vision loss. Lenadogene nolparvovec gene therapy was developed as a treatment for patients with vision loss from LHON caused by the most prevalent m.11778G > A mitochondrial DNA point mutation in the MT-ND4 gene. Lenadogene nolparvovec is a replication-defective recombinant adeno-associated virus vector 2 serotype 2 (AAV2/2), encoding the human wild-type MT-ND4 protein. Lenadogene nolparvovec was administered by intravitreal injection (IVT) in LHON patients harboring the m.11778G > A ND4 mutation in a clinical development program including one phase 1/2 study (REVEAL), three phase 3 pivotal studies (REVERSE, RESCUE, REFLECT), and one long-term follow-up study (RESTORE, the follow-up of REVERSE and RESCUE patients). Case presentation: A 67-year-old woman with MT-ND4 LHON, included in the REVERSE clinical study, received a unilateral IVT of lenadogene nolparvovec in the right eye and a sham injection in the left eye in May 2016, 11.4 months and 8.8 months after vision loss in her right and left eyes, respectively. The patient had a normal brain magnetic resonance imaging with contrast at the time of diagnosis of LHON. Two years after treatment administration, BCVA had improved in both eyes. The product was well tolerated with mild and resolutive anterior chamber inflammation in the treated eye. In May 2019, the patient was diagnosed with a right temporal lobe glioblastoma, IDH-wildtype, World Health Organization grade 4, based on histological analysis of a tumor excision. The brain tumor was assessed for the presence of vector DNA by using a sensitive validated qPCR assay targeting the ND4 sequence of the vector. Conclusion: ND4 DNA was not detected (below 15.625 copies/μg of genomic DNA) in DNA extracted from the brain tumor, while a housekeeping gene DNA was detected at high levels. Taken together, this data shows the absence of detection of lenadogene nolparvovec in a brain tumor (glioblastoma) of a treated patient in the REVERSE clinical trial 3 years after gene therapy administration, supporting the long-term favorable safety of lenadogene nolparvovec

The Hubble Diagram to Redshift >6 from 69 Gamma-Ray Bursts

One of the few ways to measure the properties of Dark Energy is to extend the Hubble daigram (HD) to higher redshifts with Gamma-Ray Bursts (GRBs). GRBs have at least five properties (their spectral lag, variability, spectral peak photon energy, time of the jet break, and the minimum rise time) which have correlations to the luminosity of varying quality. In this paper, I construct a GRB HD with 69 GRBs over a redshift range of 0.17 to >6, with half the bursts having a redshift larger than 1.7. This paper uses over 3.6 times as many GRBs and 12.7 times as many luminosity indicators as any previous GRB HD work. For the gravitational lensing and Malmquist biases, I find that the biases are small, with an average of 0.03 mag and an RMS scatter of 0.14 mag in the distance modulus. The GRB HD is well-behaved and nicely delineates the shape of the HD. The reduced chi-square for the fit to the concordance model is 1.05 and the RMS scatter about the concordance model is 0.65 mag. This accuracy is just a factor of 2.0 times that gotten for the same measure from all the big supernova surveys. I fit the GRB HD to a variety of models, including where the Dark Energy has its equation of state parameter varying as w(z)=w_0 + w_a z/(1+z). I find that the concordance model is consistent with the data. That is, the Dark Energy can be described well as a Cosmological Constant that does not change with time. (abridged)Comment: ApJ in press, 88 pages, 15 figure

From gene-discovery to gene-tailored clinical management: 25 years of research in channelopathies and cardiomyopathies.

In the early nineties, few years before the birth of Europace, the clinical and scientific world of familial arrhythmogenic conditions was revolutionized by the identification of the first disease-causing genes. The explosion of genetic studies over a 15-year period led to the discovery of major disease-causing genes in practically all channelopathies and cardiomyopathies, bringing insight into the pathophysiological mechanisms of these conditions. The birth of next generation sequencing allowed a further step forward and other significant genes, as CALM1-3 in channelopathies and FLN C and TTN in cardiomyopathies were identified. Genotype-phenotype studies allowed the implementation of the genetic results in diagnosis, risk stratification, and therapeutic management with a different level of evidence in different arrhythmogenic conditions. The influence of common genetic variants, i.e. SNPs, on disease manifestation was proved in mid-twenties, and in the last 10 years with the advent of genome-wide association studies performed in familial arrhythmogenic diseases, the concept of polygenic risk score has been consolidated. Now, we are at the start of another amazing phase, i.e. the initiation of first gene therapy clinical trials

The epidemiology and natural history of Crohn’s disease in population-based patient cohorts from North America: a systematic review

To quantify, through systematic review, the epidemiology and natural history of Crohn’s disease in North America. Methods:  The selected articles contained: (i) population-based samples of patients followed from the time of diagnosis; and (ii) objective diagnostic criteria for disease. Studies on the natural history of Crohn’s disease also contained sufficient follow-up. Data collection and analysis:  For prevalence studies, data on the incidence, prevalence, gender and age at diagnosis were extracted. For natural history studies, data on the disease activity, use of medications and surgery were extracted. Main results:  The prevalence of Crohn’s disease in North America ranges from 26.0 to 198.5 cases per 100 000 persons. The incidence rates range from 3.1 to 14.6 cases per 100 000 person-years. Most patients have a chronic intermittent disease course, while 13% have an unremitting disease course and 10% have a prolonged remission. Less than half require corticosteroids at any point. During any given year, approximately 10% are treated with corticosteroids and 30% are treated with 5-aminosalicylates. Up to 57% of patients require at least one surgical resection. Conclusions:  Between 400 000 and 600 000 patients in North America have Crohn’s disease, and the natural history is marked by frequent exacerbations requiring treatment with corticosteroids, 5-aminosalicylate products and surgery.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72031/1/j.1365-2036.2002.01140.x.pd

Teachers as writers: a systematic review

This paper is a critical literature review of empirical work from 1990-2015 on teachers as writers. It interrogates the evidence on teachers’ attitudes to writing, their sense of themselves as writers and the potential impact of teacher writing on pedagogy or student outcomes in writing. The methodology was carried out in four stages. Firstly, educational databases keyword searches located 438 papers. Secondly, initial screening identified 159 for further scrutiny, 43 of which were found to specifically address teachers’ writing identities and practices. Thirdly, these sources were screened further using inclusion/exclusion criteria. Fourthly, the 22 papers judged to satisfy the criteria were subject to in-depth analysis and synthesis. The findings reveal that the evidence base in relation to teachers as writers is not strong, particularly with regard to the impact of teachers’ writing on student outcomes. The review indicates that teachers have narrow conceptions of what counts as writing and being a writer and that multiple tensions exist, relating to low self-confidence, negative writing histories, and the challenge of composing and enacting teacher and writer positions in school. However, initial training and professional development programmes do appear to afford opportunities for reformulation of attitudes and sense of self as writer

Photometry and Spectroscopy of GRB 030329 and Its Associated Supernova 2003dh: The First Two Months

We present extensive optical and infrared photometry of the afterglow of gamma-ray burst (GRB) 030329 and its associated supernova (SN) 2003dh over the first two months after detection (2003 March 30-May 29 UT). Optical spectroscopy from a variety of telescopes is shown and, when combined with the photometry, allows an unambiguous separation between the afterglow and supernova contributions. The optical afterglow of the GRB is initially a power-law continuum but shows significant color variations during the first week that are unrelated to the presence of a supernova. The early afterglow light curve also shows deviations from the typical power-law decay. A supernova spectrum is first detectable ~7 days after the burst and dominates the light after ~11 days. The spectral evolution and the light curve are shown to closely resemble those of SN 1998bw, a peculiar Type Ic SN associated with GRB 980425, and the time of the supernova explosion is close to the observed time of the GRB. It is now clear that at least some GRBs arise from core-collapse SNe.Comment: 57 pages, 13 figures, accepted by ApJ, revised per referee's comments, includes full photometry table. Data available at ftp://cfa-ftp.harvard.edu/pub/kstanek/GRB030329 or through WWW at http://cfa-www.harvard.edu/cfa/oir/Research/GRB