Topical Flunixin Meglumine Effects on Pain Associated Biomarkers after Dehorning

Twenty-four calves were dehorned and treated with either topical flunixin meglumine formulated for systemic absorption or a placebo. Biomarkers associated with pain were evaluated for up to 72 hour after the dehorning procedure. Plasma cortisol concentrations, 90 minutes post-dehorning, and mechanical nociception threshold at the control site were the only tested biomarkers where a significant difference was demonstrated. No other differences of biomarkers between the two dehorned groups were observed for any time points. Although this product is easy to dose and dispense, its effects on pain biomarkers appears to be negligible

Cross-accent intelligibility of speech in noise: Long-term familiarity and short-term familiarization

Listeners must cope with a great deal of variability in the speech signal, and thus theories of speech perception must also account for variability, which comes from a number of sources, including variation between accents. It is well-known that there is a processing cost when listening to speech in an accent other than one’s own, but recent work has suggested that this cost is reduced when listening to a familiar accent widely represented in the media, and/or when short amounts of exposure to an accent are provided. Little is known, however, about how these factors (long-term familiarity and short-term familiarization with an accent) interact. The current study tested this interaction by playing listeners difficult-to-segment sentences in noise, before and after a familiarization period where the same sentences were heard in the clear, allowing us to manipulate short-term familiarization. Listeners were speakers of either Glasgow English or Standard Southern British English, and they listened to speech in either their own or the other accent, thereby allowing us to manipulate long-term familiarity. Results suggest that both long-term familiarity and short-term familiarization mitigate the perceptual processing costs of listening to an accent that is not one’s own, but seem not to compensate for them entirely, even when the accent is widely heard in the media

[F-18]FDG-PET/CT to prevent futile surgery in indeterminate thyroid nodules:a blinded, randomised controlled multicentre trial

Purpose To assess the impact of an [F-18]FDG-PET/CT-driven diagnostic workup to rule out malignancy, avoid futile diagnostic surgeries, and improve patient outcomes in thyroid nodules with indeterminate cytology. Methods In this double-blinded, randomised controlled multicentre trial, 132 adult euthyroid patients with scheduled diagnostic surgery for a Bethesda III or IV thyroid nodule underwent [F-18]FDG-PET/CT and were randomised to an [F-18] FDG-PET/CT-driven or diagnostic surgery group. In the [F-18]FDG-PET/CT-driven group, management was based on the [F-18]FDG-PET/CT result: when the index nodule was visually [F-18]FDG-positive, diagnostic surgery was advised; when [F-18]FDG-negative, active surveillance was recommended. The nodule was presumed benign when it remained unchanged on ultrasound surveillance. In the diagnostic surgery group, all patients were advised to proceed to the scheduled surgery, according to current guidelines. The primary outcome was the fraction of unbeneficial patient management in one year, i.e., diagnostic surgery for benign nodules and active surveillance for malignant/borderline nodules. Intention-to-treat analysis was performed. Subgroup analyses were performed for non-Hurthle cell and Hurthle cell nodules. Results Patient management was unbeneficial in 42% (38/91 [95% confidence interval [CI], 32-53%]) of patients in the [F-18] FDG-PET/CT-driven group, as compared to 83% (34/41 [95% CI, 68-93%]) in the diagnostic surgery group (p < 0.001). [F-18]FDG-PET/CT-driven management avoided 40% (25/63 [95% CI, 28-53%]) diagnostic surgeries for benign nodules: 48% (23/48 [95% CI, 33-63%]) in non-Hurthle cell and 13% (2/15 [95% CI, 2-40%]) in I-Liable cell nodules (p = 0.02). No malignant or borderline tumours were observed in patients under surveillance. Sensitivity, specificity, negative and positive predictive value, and benign call rate (95% CI) of [F-18]FDG-PET/CT were 94.1% (80.3-99.3%), 39.8% (30.0-50.2%), 95.1% (83.5-99.4%), 35.2% (25.4-45.9%), and 31.1% (23.3-39.7%), respectively. Conclusion An [F-18]FDG-PET/CT-driven diagnostic workup of indeterminate thyroid nodules leads to practice changing management, accurately and oncologically safely reducing futile surgeries by 40%. For optimal therapeutic yield, application should be limited to non-Hurthle cell nodules

Allosteric control of Ubp6 and the proteasome via a bidirectional switch

The interplay of the proteasome and deubiquitinase Ubp6 is crucial for the degradation of ubiquitylated substrates. Here, the authors provide structural insights into the allosteric mechanism by which the activities of both Ubp6 and the proteasome are regulated. The proteasome recognizes ubiquitinated proteins and can also edit ubiquitin marks, allowing substrates to be rejected based on ubiquitin chain topology. In yeast, editing is mediated by deubiquitinating enzyme Ubp6. The proteasome activates Ubp6, whereas Ubp6 inhibits the proteasome through deubiquitination and a noncatalytic effect. Here, we report cryo-EM structures of the proteasome bound to Ubp6, based on which we identify mutants in Ubp6 and proteasome subunit Rpt1 that abrogate Ubp6 activation. The Ubp6 mutations define a conserved region that we term the ILR element. The ILR is found within the BL1 loop, which obstructs the catalytic groove in free Ubp6. Rpt1-ILR interaction opens the groove by rearranging not only BL1 but also a previously undescribed network of three interconnected active-site-blocking loops. Ubp6 activation and noncatalytic proteasome inhibition are linked in that they are eliminated by the same mutations. Ubp6 and ubiquitin together drive proteasomes into a unique conformation associated with proteasome inhibition. Thus, a multicomponent allosteric switch exerts simultaneous control over both Ubp6 and the proteasome

Half-metallic ferromagnets and their magneto-optical properties

We have calculated the electronic structure of PtMnSb in order to explain the very high magneto-optical Kerr effect (over 2.5° at 720 nm at room-temperature) of this compound. It is shown that this behavior is related to the unusual electronic properties of PtMnSb: it is a half-metallic ferromagnet like NiMnSb. The extreme asymmetry in the electronic structure of these compounds—metallic behavior for one spin direction and at the same time semiconducting behavior for the other spin direction—is responsible for the unusual magneto-optical properties

Half-metallicity and Slater-Pauling behavior in the ferromagnetic Heusler alloys

Introductory chapter for the book "Halfmetallic Alloys - Fundamentals and Applications" to be published in the series Springer Lecture Notes on Physics, P. H. Dederichs and I. Galanakis (eds). It contains a review of the theoretical work on the half-metallic Heusler alloys.Comment: Introductory chapter for the book "Halfmetallic Alloys - Fundamentals and Applications" to be published in the series Springer Lecture Notes on Physics, P. H. Dederichs and I. Galanakis (eds

Архетип свобода у контексті французької політичної теорії та історії

Розглянуто сучасні підходи щодо аналізу політичної ментальності. У межах політологічного аналізу окреслено коло проблем, які потребують вирішення з використанням підходів психології. Зроблено висновок про те, що архетип “свобода” становить важливий елемент політичної ментальності французів.Modern approaches of analysis of political mentality are considered. Within the limits of political science analysis outlined circle of problems which need decision with the use of approaches of psychology. A conclusion is done that archetype freedom makes the important element of political mentality of French’s

Activating mutations of the GNAQ gene: a frequent event in primary melanocytic neoplasms of the central nervous system

Primary melanocytic neoplasms of the central nervous system (CNS) are uncommon neoplasms derived from melanocytes that normally can be found in the leptomeninges. They cover a spectrum of malignancy grades ranging from low-grade melanocytomas to lesions of intermediate malignancy and overtly malignant melanomas. Characteristic genetic alterations in this group of neoplasms have not yet been identified. Using direct sequencing, we investigated 19 primary melanocytic lesions of the CNS (12 melanocytomas, 3 intermediate-grade melanocytomas, and 4 melanomas) for hotspot oncogenic mutations commonly found in melanocytic tumors of the skin (BRAF, NRAS, and HRAS genes) and uvea (GNAQ gene). Somatic mutations in the GNAQ gene at codon 209, resulting in constitutive activation of GNAQ, were detected in 7/19 (37%) tumors, including 6/12 melanocytomas, 0/3 intermediate-grade melanocytomas, and 1/4 melanomas. These GNAQ-mutated tumors were predominantly located around the spinal cord (6/7). One melanoma carried a BRAF point mutation that is frequently found in cutaneous melanomas (c.1799 T>A, p.V600E), raising the question whether this is a metastatic rather than a primary tumor. No HRAS or NRAS mutations were detected. We conclude that somatic mutations in the GNAQ gene at codon 209 are a frequent event in primary melanocytic neoplasms of the CNS. This finding provides new insight in the pathogenesis of these lesions and suggests that GNAQ-dependent mitogen-activated kinase signaling is a promising therapeutic target in these tumors. The prognostic and predictive value of GNAQ mutations in primary melanocytic lesions of the CNS needs to be determined in future studies