Miracle-dz/UniFAR-FTUs huggingface dataset:
Neospora caninum in beef herds in New South Wales, Australia. 1: seroprevalence study

OBJECTIVE To determine the seroprevalence of Neospora caninum antibodies in beef breeding herds across New South Wales (NSW) and to determine if there are any differences associated with geographic location and other herd-level factors. METHODS Cross-sectional survey of beef breeding cows (n = 3298) from 63 properties (approximately 55 cows per herd) sampled randomly from six regions in NSW using a multistage survey design. Samples were tested by ELISA for N. caninum. Seroprevalence was determined at animal and herd levels, using an analysis approach to account for stratification, sample weighting and within-herd clustering. RESULTS Animal-level seroprevalence ranged from 1.8% to 11.3% across regions and the overall animal seroprevalence for NSW was 5.9%. The mean within-herd seroprevalence was 5.2%. The herd seroprevalence ranged from 50% to 92%, with an overall point estimate for NSW of 63.8% (using ≥ 1 animal positive = herd positive). The within-herd seroprevalence ranged from 1.6% to 32.7% Prevalence and associated confidence limits were adjusted for the design of the survey. CONCLUSIONS Overall, about two-thirds of all herds in NSW showed evidence of infection, but the seroprevalence of N. caninum in individual beef cattle in NSW was low to moderate (1.8-11.3%). Significant differences occurred between regions. The risk for herds being positive for N. caninum was associated with geographic factors, particularly in the Mid-North Coast Region.
Visceral adiposity index is associated with insulin sensitivity and adipocytokine levels in newly diagnosed acromegalic patients.

CONTEXT The visceral adiposity index (VAI) has proved to be a marker of visceral adipose dysfunction, strongly associated with insulin sensitivity in both the general and specific populations of patients at metabolic risk. OBJECTIVE The objective of the study was to test VAI as a useful tool to assess early metabolic risk in acromegaly. PATIENTS Twenty-four newly diagnosed acromegalic patients (11 women and 13 men, aged 54.9 ± 13.6 yr) were grouped into those with normal (group A, n = 13, 54.2%) and those with high VAI (group B, n = 11, 45.8%). OUTCOME MEASURES Glucose, hemoglobin A1c, nadir and area under the curve (AUC) of GH (AUC(GH)) during the oral glucose tolerance test, AUC(Cpeptide) during a mixed-meal tolerance test, M value during euglycemic-hyperinsulinemic clamp, oral dispositional index (DIo), each component of the metabolic syndrome, leptin, adiponectin, TNF-α, and IL-6. RESULTS The VAI value was positively correlated with the age of patients (ρ = 0.408; P = 0.048), tumor volume (ρ = 0.638; P = 0.001), basal GH (ρ = 0.622; P = 0.001), nadir GH (ρ = 0.534; P = 0.007), AUC(GH) (ρ = 0.603; P = 0.002), IGF-I (ρ = 0.618; P = 0.001), TNF-α (ρ = 0.512; P = 0.010), and AUC(Cpeptide) (ρ = 0.715; p<0.001) and negatively with adiponectin (ρ = -0.766; P < 0.001), M value (ρ = -0.818; P < 0.001), and DIo (ρ = -0.512; P = 0.011). Patients with high VAI showed significantly higher basal GH levels (P = 0.018), AUC(GH) (P = 0.047), IGF-I (P = 0.047), AUC(Cpeptide) (P = 0.018), lower M value (P < 0.001), DIo (P = 0.006), and adiponectin levels (P < 0.001), despite the absence of a significantly higher prevalence in the overt metabolic syndrome and glucose tolerance abnormalities. AUC(GH) proved to be the main independent factor influencing VAI. CONCLUSIONS In acromegaly, VAI appears to be associated with disease activity, adiponectin levels, and insulin sensitivity and secretion and is influenced independently by GH levels. VAI could therefore be used as an easy and useful new tool in daily clinical practice for the assessment of early metabolic risk associated with active acromegaly.
Augmentation of Anterior Vertebral Body Screw Fixation by an Injectable, Biodegradable Calcium Phosphate Bone Substitute

Study Design. A biomechanical study to evaluate the effects of a biodegradable calcium phosphate (Ca-P) bone substitute on the fixation strength and bending rigidity of vertebral body screws. Objectives. To determine if an injectable, biodegradable Ca-P bone substitute provides significant augmentation of anterior vertebral screw fixation in the osteoporotic spine. Summary of Background Data. Polymethylmethacrylate (PMMA) augmented screws have been used clinically; however, there is concern about thermal damage to the neural elements during polymerization of the PMMA as well as its negative effects on bone remodeling. Injectable, biodegradable Ca-P bone substitutes have shown enhanced fixation of pedicle screws. Methods. Sixteen fresh cadaveric thoracolumbar vertebrae were randomly divided into two groups: control (no augmentation) (n = 8) and Ca-P bone substitute augmentation (n = 8) groups. Bone–screw fixation rigidity in bending was determined initially and after 105 cycles, followed by pullout testing of the screw to failure to determine pullout strength and stiffness. Results. The bone–screw bending rigidity for the Ca-P bone substitute group was significantly greater than the control group, initially (58%) and after cyclic loading (125%). The pullout strength for Ca-P bone substitute group (1848 ± 166 N) was significantly greater than the control group (665 ± 92 N) (P < 0.01). Stiffness in pullout for the Ca-P bone substitute groups (399 ± 69 N/mm) was significantly higher than the control group (210 ± 51 N/mm) (P < 0.01). Conclusion. This study demonstrated that augmentation of anterior vertebral body screw fixation with a biodegradable Ca-P bone substitute is a potential alternative to the use of PMMA cement.
Credit Limits, Stress Testing and Model Risk for Capital Metrics

The topics of Economic Capital modelling, reverse stress testing and credit limits are inextricably intertwined as they all focus on exceptional loss events. In this paper, we use the KVA framework in to frame these three topics within a single unified approach. We propose setting credit limits based on an incremental KVA metric interpreted as a measure of capital consumption for each individual client. Compared to Potential Future Exposure (PFE), incremental KVA is more risk sensitive as i) it is portfolio sensitive and detects cross-selling opportunities, ii) captures wrong-way-risk, iii) accounts for idiosyncratic features such as granularity and credit risk concentration, iv) measures also other risks besides the default of the counterparty such as CVA and FVA mark-to-market losses and is suitable to generalisations driven by regulatory changes such as MVA.A reverse stress testing exercise based on KVA metrics reveals stress scenarios of two kinds: the ones where losses are due to an idiosyncratic vulnerability of the portfolio and the ones tied to systemic risk and the credit cycle. The latter are completely missed by the PFE, although crucially important during periods of market distress.Since different pricing models tend to diverge the most for stressed scenarios, model risk has a material impact on capital projections and, consequently, on the KVA metric. We discuss model risk comparing Gaussian interest rate models admitting arbitrarily negative rates with alternative models where rates are bounded from below.
Decompression alone versus decompression with limited fusion for treatment of degenerative lumbar scoliosis in the elderly patient

ABSTRACT Study design: Retrospective cohort study. Objective: To analyze the surgical results of a group of patients older than 65 years treated for mild degenerative lumbar scoliosis (<30°) with stenosis, treated with decompression alone or decompression and limited fusion. Methods: We evaluated 55 patients, all older than 65 years from our prospectively collected database with mild degenerative scoliosis (<30°) and stenosis who underwent surgery. Laminectomy alone was performed in 16 patients, and laminectomy and limited fusion in 39 patients. Mean follow-up was 4.6 years in the decompression group and 5.0 years in the fusion group. Clinical results were graded by patients’ self-reported satisfaction and length of symptom-free period to recurrence. Results: In the decompression alone group, 6 (37%) of 16 patients developed recurrent stenosis at the previously decompressed level and five developed recurrence within 6 months postoperatively versus the decompression and fusion group where 3 (8%) of 39 (P = .0476) developed symptomatic stenosis supra adjacent to the fusion. Of 16 patients in the decompression alone group, 12 (75%) had recurrence of symptoms by the 5-year follow-up period versus only 14 (36%) patients in the decompression and fusion group (P = .016). Adjacent segment degenerative changes were common in the fusion group, but only 7% developed symptomatic stenosis. Conclusions: Decompression with limited fusion prevents early return of stenotic symptoms compared with decompression alone in the setting of mild degenerative scoliosis (<30°) and symptomatic stenosis in patients 65 years and older. Final class of evidence—prognosis Study design RCT Cohort • Case control Case series Methods Concealed allocation (RCT) Intention to treat (RCT) Blinded/independent evaluation of primary outcome F/U ≥ 85% • Adequate sample size Control for confounding Overall class of evidence III The definiton of the different classes of evidence is available here.
A phase II study of imatinib mesylate (IM) for patients with advanced melanoma harboring somatic alterations of KIT.

9001 Background: Three prior phase II studies of Imatinib mesylate (IM) in 62 pts with advanced melanoma reported only 1 response in a pt with acral melanoma. A proportion of melanomas arising from acral, mucosal, and chronic sun damaged (CSD) sites are characterized by KIT mutations (mut) or amplifications (amp) and we hypothesized that this subset of tumors would be sensitive to IM. We thus designed this phase II study of IM restricted to pts with melanoma harboring such alterations in KIT. METHODS Pts with unresectable melanoma arising from acral, mucosal, and CSD sites whose tumor harbored a 4q12 amp by FISH or mut in KIT and who had measureable disease by RECIST were eligible. Pts received IM 400 mg BID continually. Response was assessed every cycle (6 wks). A Simon 2-stage design was employed where initially 16 pts would be treated; if ≥ 2 responses were observed, a total of 25 pts would be enrolled. If ≥5 responses were seen in 25 pts, the study was to be considered positive. RESULTS Of 81 pt tumors screened, 17 (21%) had a KITmut or amp: 5/22 (23%) acral, 12/45 (27%) mucosal, 0/13 (0%) CSD, 0/1 (0%) unknown primary. 12 (15%) had a mut only; 4 (5%) had an amplification only; 1 (2%) had both. Thus far, 7 have been treated, with 5 currently evaluable for response. Median age: 64 yrs (range, 61-86); 2 male/5 female; median KPS: 90 (range, 80- 90); median # of prior therapies: 1 (range, 0-4). 3 pts (43%) achieved a PR (18 wks - exon 13 mut; 21 wks, ongoing - exon 11 mut; 18 wks, ongoing - exon 11 mut & amp); 2 pts (28%) achieved SD (12 wks - exon 11 mut; 11 wks - amp). 3 pts required a dose reduction to 400 mg QD for rash, GI toxicity and fatigue. 1 pt required a second dose reduction to 300 mg QD for visual changes. CONCLUSIONS In this pt population, 21% of tumors are characterized by mut or amp of KIT. The 3 responses observed have allowed expansion to the second stage of enrollment which is currently on-going. While IM has limited activity in a non-selected melanoma pt population, a substantial proportion of melanomas harboring KIT mut or amp appear to respond. It may be possible to identify appropriate pts prospectively for treatment with IM. (Supported by R01FD003445-01, ASCO YIA, N01CM62206, and the Live4Life Foundation.) No significant financial relationships to disclose.
Epigenetic Regulation Contributes to Urocortin‐Enhanced Midbrain Dopaminergic Neuron Differentiation

The production of midbrain dopaminergic (mDA) neurons requires precise extrinsic inductive signals and intrinsic transcriptional cascade at a specific time point in development. Urocortin (UCN) is a peptide of the corticotropin‐releasing hormone family that mediates various responses to stress. UCN was first cloned from adult rat midbrain. However, the contribution of UCN to the development of mDA neurons is poorly understood. Here, we show that UCN is endogenously expressed in the developing ventral midbrain (VM) and its receptors are exhibited in Nurr1+ postmitotic mDA precursors and TH+ neurons, suggesting possible roles in regulating their terminal differentiation. UCN treatment increased DA cell numbers in rat VM precursor cultures by promoting the conversion of Nurr1+ precursors into DA neurons. Furthermore, neutralization of secreted UCN with anti‐UCN antibody resulted in a reduction in the number of DA neurons. UCN induced an abundance of acetylated histone H3 and enhanced late DA regulator Nurr1, Foxa2, and Pitx3 expressions. Using pharmacological and RNA interference approaches, we further demonstrated that histone deacetylase (HDAC) inhibition and late transcriptional factors upregulation contribute to UCN‐mediated DA neuron differentiation. Chromatin immunoprecipitation analyses revealed that UCN promoted histone acetylation of chromatin surrounding the TH promoter by directly inhibiting HDAC and releasing of methyl CpG binding protein 2‐CoREST‐HDAC1 repressor complex from the promoter, ultimately leading to an increase in Nurr1/coactivators‐mediated transcription of TH gene. Moreover, UCN treatment in vivo also resulted in increased DA neuron differentiation. These findings suggest that UCN might contribute to regulate late mDA neuron differentiation during VM development. Stem Cells 2015;33:1601–1617
Albinterferon Alfa-2b was not inferior to pegylated interferon-α in a randomized trial of patients with chronic hepatitis C virus genotype 1.

BACKGROUND & AIMS The current standard of care for patients with chronic hepatitis C virus (HCV) genotype 1 is once-weekly pegylated interferon-α (Peg-IFNα) plus daily ribavirin for 48 weeks. We evaluated the efficacy/safety of albinterferon alfa-2b (albIFN), a novel, long-acting, genetic fusion polypeptide of albumin and IFNα-2b. METHODS In the phase 3 ACHIEVE-1 trial, 1331 patients were assigned equally to 3 open-label, 48-week treatment groups: Peg-IFNα-2a 180 μg every week, or albIFN 900 or 1200 μg every 2 weeks administered subcutaneously, with weight-based oral ribavirin 1000-1200 mg/day. During the study, the data monitoring committee recommended dose modification for all patients receiving albIFN 1200 μg to 900 μg because of increased pulmonary adverse events (AEs) in the 1200-μg arms of both ACHIEVE studies. Main outcome measure was sustained virologic response (SVR; undetectable serum HCV RNA at week 72). RESULTS Intention-to-treat SVR rates were 51.0% (225/441), 48.2% (213/442), and 47.3% (208/440) with Peg-IFNα-2a, and albIFN 900 and 1200 μg, respectively. The primary objective of showing noninferiority of albIFN 900 μg (P < .001) and 1200 μg (P = .003) vs Peg-IFNα-2a for SVR was achieved. Multivariate modeling indicated consistency of treatment effect across subgroups. Serious/severe AE rates were 23.1%, 24.0%, 28.2%; treatment discontinuation rates because of AEs were 4.1%, 10.4%, 10.0%; discontinuation rates because of respiratory AEs were 0%, 0.9%, 1.6%; with Peg-IFNα-2a, and albIFN 900 and 1200 μg, respectively. Hematologic abnormality rates were comparable across the Peg-IFNα-2a and albIFN 900-μg groups. CONCLUSIONS albIFN 900 μg every 2 weeks showed comparable efficacy, with similar serious/severe AE rates, although with a higher discontinuation rate, vs Peg-IFNα-2a in patients with chronic HCV genotype 1.
A Prospective Study of Upper Aerodigestive Tract Manifestations of Mucous Membrane Pemphigoid

Abstract: We conducted a prospective study between 1995 and 2002 to investigate nose and throat (NT) manifestations of mucous membrane pemphigoid (MMP). One hundred ten consecutive patients with clinical, histologic, and immunologic criteria of MMP were seen in 2 referral centers for bullous diseases. They were systematically asked about the existence of persistent NT symptoms. Patients who had any were examined with a flexible nasopharyngolaryngoscope by the same otorhinolaryngologist. When possible, NT mucous membrane (MM) biopsies were taken for direct immunofluorescence (IF) assays to determine lesion specificity. Thirty-eight (35%) patients (23 F/15 M; mean age, 58.5 yr) had the following NT symptoms: 35 (92%) nasal, 19 (50%) pharyngeal, and 10 (26%) laryngeal. Five (13%) had acute dyspnea. Thirty-three (87%) of the 38 symptomatic patients had lesions at physical examination: 30 (79%) nasal, 6 (16%) pharyngeal, and 19 (50%) laryngeal. Laryngeal involvement was asymptomatic in 11 patients. Lesions were mainly atrophic rhinitis and oropharyngeal and epiglottal erosions. Nasal valves, choanae, pharynx, and/or larynx were severely scarred in 7 (18%) patients, causing the death of 3. Direct IF showed malpighian epithelium associated with linear immune deposits (IgG, IgA, or C3) along the chorioepithelial junction in all 18 biopsies performed, including those of 4 symptomatic patients without lesions at physical examination. The presence of severe ophthalmologic lesions (p = 0.02) and ≥3 sites involved other than NT (p = 0.02) were predictive of laryngeal involvement. In contrast, laryngeal symptoms, disease duration, HLA DQB1*0301, and smoking were not significantly associated with laryngeal lesions. In conclusion, at least 35% of MMP patients had NT involvement. Atrophic rhinitis was the most frequent lesion. The most severe were the laryngeal lesions that were significantly associated with severe ocular involvement and disseminated disease, and could be fatal. Our results highlight the necessity of a multidisciplinary approach to MMP management to assure early diagnosis of NT involvement, to guide therapeutic choices, and to improve patient survival and functional outcomes. Abbreviations: BMZ = basement membrane zone, BP = bullous pemphigoid, EBA = epidermolysis bullosa acquisita, HLA = human leukocyte antigen, IEM = immunoelectron microscopy, IF = immunofluorescence, MM = mucous membrane, MMP = mucous membrane pemphigoid, NT = nose and throat, SSS = salt-split skin.
Morphogenesis of Mimivirus and Its Viral Factories: an Atomic Force Microscopy Study of Infected Cells

ABSTRACT Amoebas infected with mimivirus were disrupted at sequential stages of virus production and were visualized by atomic force microscopy. The development of virus factories proceeded over 3 to 4 h postinfection and resulted from the coalescence of 0.5- to 2-μm vesicles, possibly bearing nucleic acid, derived from either the nuclear membrane or the closely associated rough endoplasmic reticulum. Virus factories actively producing virus capsids on their surfaces were imaged, and this allowed the morphogenesis of the capsids to be delineated. The first feature to appear on a virus factory surface when a new capsid is born is the center of a stargate, which is a pentameric protein oligomer. As the arms of the stargate grow from the pentamer, a rough disk the diameter of a capsid thickens around it. This marks the initial emergence of a protein-coated membrane vesicle. The capsid self-assembles on the vesicle. Hillocks capped by different pentameric proteins spontaneously appear on the emerging vesicle at positions that are ultimately occupied by 5-fold icosahedral vertices. A lattice of coat protein nucleates at each of the 5-fold vertices, but not at the stargate, and then spreads outward from the vertices over the surface, merging seamlessly to complete the icosahedral capsid. Filling with DNA and associated proteins occurs by the transfer of nucleic acid from the interior of the virus factory into the nearly completed capsids. The portal, through which the DNA enters, is sealed by a plug of protein having a diameter of about 40 nm. A layer of integument protein that anchors the surface fibers is acquired by the passage of capsids through a membrane enriched in the protein. The coating of surface fibers is similarly acquired when the integument protein-coated capsids pass through a second membrane that has a forest of surface fibers embedded on one side.
Race, Class and Religion in the Southern Realignment

Many studies have documented a secular partisan realignment in southern politics, particularly the movement of southern whites to the Republican Party. This has spawned an ongoing debate about the main sources of this realignment. The most common explanation emphasizes racial attitudes and the politics of civil rights. However, some recent studies provide two alternative explanations: (1) economic attitudes and class politics; and (2) religion and the politics of moral values. To date, few studies assess the relative impact of all three factors – many examine one or two of these factors, but not all three simultaneously. We use the series of surveys conducted by the American National Election Studies through 2008 to examine the degree to which issues and values related to race, economics, and morality predict partisanship among southern whites over the past several decades. We find that a wider array of policy attitudes and values predict partisanship today than in the past.
Finite Element Based Monte Carlo Simulation of Option Prices on Lévy Driven Assets

This paper extends the simulation algorithm by Andreasen & Huge (2011) to the simulation of option prices and deltas on Levy driven assets. The simulation is performed relying on the inverse transition matrix of the discretized PDE. Each row describes the evolution of option prices and can thus be seen as the underlying’s transition probability distribution. We demonstrate how one can get accurate prices and deltas of European options on VG and CGMY via Monte Carlo simulations.
Light and electron microscope study of GABA‐immunoreactive neurones in Lamina III of rat spinal cord

In order to determine whether different morphological types of neurone in lamina III of rat spinal dorsal horn contain different neurotransmitters, a combined Golgi and immunocytochemical study was performed. Semithin sections through the cell bodies of 52 Golgi‐impregnated neurones in this lamina were tested with antisera to GABA and glycine. Thirty of these cells were immunoreactive with anti‐GABA antiserum and 25 of these also showed glycine‐like immunoreactivity. These cells had dendrites which were oriented along the rostrocaudal axis and occupied lamina III, with some extension into lamina IV and the ventral half of lamina II. Although some of the nonimmunoreactive cells had similar morphology, many of them had dendrites which passed in a dorsal and/or ventral direction and crossed laminar boundaries. Three of the neurones which were immunoreactive with both antisera were examined with the electron microscope. These cells received a variety of synapses including some from axons which resembled low threshold myelinated mechanoreceptive primary afferents.