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Epilepsy surgery is the therapy of choice for many patients with drug‐resistant focal epilepsy. Recognizing and describing ictal and interictal patterns with intracranial electroencephalography (EEG) recordings is important in order to most efficiently leverage advantages of this technique to accurately delineate the seizure‐onset zone before undergoing surgery. In this seminar in epileptology, we address learning objective “1.4.11 Recognize and describe ictal and interictal patterns with intracranial recordings” of the International League against Epilepsy curriculum for epileptologists. We will review principal considerations of the implantation planning, summarize the literature for the most relevant ictal and interictal EEG patterns within and beyond the Berger frequency spectrum, review invasive stimulation for seizure and functional mapping, discuss caveats in the interpretation of intracranial EEG findings, provide an overview on special considerations in children and in subdural grids/strips, and review available quantitative/signal analysis approaches. To be as practically oriented as possible, we will provide a mini atlas of the most frequent EEG patterns, highlight pearls for its not infrequently challenging interpretation, and conclude with two illustrative case examples. This article shall serve as a useful learning resource for trainees in clinical neurophysiology/epileptology by providing a basic understanding on the concepts of invasive intracranial EEG. Content available: Video.

Hereditary angioedema (HAE) is characterized by unpredictable, recurrent, and potentially life-threatening attacks. Garadacimab, a subcutaneous, once-monthly, fully human anti-activated factor XII monoclonal antibody in development for long-term prophylaxis (LTP), has demonstrated early and durable efficacy and favorable safety profile, and allowed most patients to achieve the HAE treatment goal of total disease control in clinical studies. Approved LTPs have demonstrated treatment-related injection-site reactions (e.g., pain, erythema, bruising). Patients have indicated a preference for new LTPs that reduce treatment burden. We characterize injection-site adverse events from the garadacimab Phase 3 clinical program.

Anne-Marie Brady, editor. Looking North, Looking South: China, Taiwan, and the South Pacific. Hackensack, NJ: World Scientific Publishing, 2010. xvi, 298 pp. Hardcover $94.00, ISBN 978-981-4304-38-2. Wei-chin Lee, editor. Taiwan's [...]

In rheumatology and other medical specialties there is a discrepancy between the widespread use and the imprecise designation of glucocorticoid treatment regimens. Verbal descriptions of glucocorticoid treatment regimens used in [...]

In this retrospective study, we compared the results of 1,283 open cholecystectomies (OCs) performed at our medical center during the pre-laparoscopic era with 1,107 laparoscopic cholecystectomies (LCs) performed from 1990 to 1992. There was no difference in the percentage of eases of acute and chronic cholecystitis in each time period (16.8% in each), nor were there differences in the patient characteristics for each group. The percent -age of patients undergoing intraoperative cholangi -ography was similar for patients with chronic chole -cystiris for each period, although the incidence of abnormal cholangiograms was lower in the laparo -scopic era (5.8% versus 15.2%, p

Thorax 2003;58:861-866 Objective: To investigate the validity of spirometric tests performed in general practice. Method: A repeated within subject comparison of spirometric tests with a 'gold standard' (spirometric tests performed [...]

The (ultra)high-pressure Western Gneiss Region of the Norwegian Caledonides represents an archetypical orogenic infrastructure of a continent–continent collision zone. To test established exhumation models, we synthesize the geochronology and structures of major basement windows and provide new ages from poorly dated areas. Migmatite U–Pb zircon samples date melt crystallization at c. 405 Ma in the Øygarden Complex, expanding the spatial extent of Devonian migmatization. Micas from shear zones in the Øygarden and Gulen domes yield 40Ar/39Ar ages mostly between 405 and 398 Ma, recording the exhumation of metamorphic core complexes. On a larger scale, the youngest ages of various geochronometers in different segments of the Western Gneiss Region show abrupt breaks (10–30 myr) across low-angle detachments and sinistral transfer zones, which also correspond to metamorphic and structural discontinuities. We explain the segmentation of the orogenic infrastructure by partitioned post-orogenic transtension due to lateral and vertical rheological contrasts in the orogenic edifice (strong cratonic foreland and orogenic wedge v. soft infrastructure). Differential crustal stretching dragged out deep levels of the orogenic crust below low-angle detachments and became progressively dominated by sinistral transfer zones. Collapse obliterated the syn-collisional structure of the orogenic root and resulted in the diachronous exhumation of distinct infrastructure segments. Supplementary material: Complete analytical results are available at https://doi.org/10.6084/m9.figshare.c.5241710 [ABSTRACT FROM AUTHOR]

The weekly Urticaria Activity Score (UAS7 range 0–42) is used to evaluate treatment response in chronic spontaneous urticaria (CSU) patients. A decrease in UAS7 of 9.5–10.5 points is considered the minimum important difference (MID) to indicate a meaningful clinical response to therapy. We explored the onset of action of remibrutinib in terms of early achievement of MID-UAS7 of 10.5 points.

Viscous crustal flow can exhume once deeply buried rocks in postorogenic metamorphic core complexes (MCCs). While migmatite domes record the flow dynamics of anatectic crust, the mechanics and kinematics of solid‐state flow in the deep crust are poorly constrained. To address this issue, we studied a deeply eroded and particularly well‐exposed MCC in the southern Western Gneiss Region of Norway. The Gulen MCC formed during Devonian transtensional collapse of the Caledonian orogeny in the footwall of the Nordfjord‐Sogn detachment zone. We developed a semiquantitative mapping scheme for ductile strain to constrain micro‐ to megascale processes, which brought eclogite‐bearing crust from the orogenic root into direct contact with Devonian supradetachment basins. The Gulen MCC comprises different structural levels with distinct metamorphic evolutions. In the high‐grade core, amphibolite‐facies structures record fluid‐controlled eclogite retrogression and coaxial flow involving vast extension‐perpendicular shortening. Detachment mylonites formed during ductile‐to‐brittle noncoaxial deformation and wrap around the core. We present a sequential 3‐D reconstruction of MCC formation. In the detachment zone, the combined effects of simple shearing, incision/excision, and erosion thinned the upper crust. Internal necking of the ductile crust was compensated by extension‐perpendicular shortening within the deep crust and resulted in differential folding of distinct crustal levels. We identify this differential folding as the main mechanism that can redistribute material within solid‐state MCCs. Our interpretation suggests a continuum of processes from migmatite‐cored to solid‐state MCCs and has implications for postorogenic exhumation of (ultra‐)high‐pressure rocks. The Earth's crust has different layers with contrasting mechanics. Rocks in the upper crust tend to break, while higher temperatures at depth make rocks flow, although very slowly. This contrast is important when continents collide forming mountain belts but also when plates drift apart and mountain ranges collapse. In SW Norway, hundreds of million years of erosion have exposed rocks that once were deep below a large mountain range (the Caledonides). Today, glacier‐polished fjords reveal large dome structures that formed when the Caledonides collapsed. Inside such a dome, we find rocks originating from different levels of the crust. Rocks and structures in the core formed at high pressures and temperatures. Wrapped around, we find rocks that deformed while they cooled down, became more resistant to flow, and finally broke apart. Above the dome, we find remnants of the upper crust, which was broken up by faults, eroded, and deposited in sedimentary basins. We reconstruct how mechanical contrasts between crustal layers brought rocks from the root of the mountain belt in contact with sediments deposited at the surface. Understanding this process is important, because it can entirely transform the crust within a—geologically speaking—short period of time. A deeply eroded and particularly well‐exposed transtensional core complex reveals mechanisms of solid‐state viscous flow in the deep crustVertical metamorphic variations and lateral strain gradients lead to differential folding of distinct crustal levelsSolid‐state flow mechanisms are similar to anatectic crust and can contribute to postorogenic exhumation of (ultra‐)high‐pressure rocks

Objective--To investigate the short term effects of corticosteroid pulse treatment (CPT) on disease activity, functional ability, and psychological wellbeing of patients with active rheumatoid arthritis (RA). Methods--Of 66 consecutive patients [...]

At present, there are no prognostic parameters unequivocally predicting treatment failure in early rheumatoid arthritis (RA) patients. We investigated whether baseline ultrasonography (US) findings of joints, when added to baseline clinical, laboratory, and radiographical data, could improve prediction of failure to achieve Disease Activity Score assessing 28 joints (DAS28) remission (<2.6) at 1 year in newly diagnosed RA patients. A multicentre cohort of newly diagnosed RA patients was followed prospectively for 1 year. US of the hands, wrists, and feet was performed at baseline. Clinical, laboratory, and radiographical parameters were recorded. Primary analysis was the prediction by logistic regression of the absence of DAS28 remission 12 months after diagnosis and start of therapy. Of 194 patients included, 174 were used for the analysis, with complete data available for 159. In a multivariate model with baseline DAS28 (odds ratio (OR) 1.6, 95% confidence interval (CI) 1.2–2.2), the presence of rheumatoid factor (OR 2.3, 95% CI 1.1–5.1), and type of monitoring strategy (OR 0.2, 95% CI 0.05–0.85), the addition of baseline US results for joints (OR 0.96, 95% CI 0.89–1.04) did not significantly improve the prediction of failure to achieve DAS28 remission (likelihood ratio test, 1.04; p= 0.31). In an early RA population, adding baseline ultrasonography of the hands, wrists, and feet to commonly available baseline characteristics did not improve prediction of failure to achieve DAS28 remission at 12 months. Clinicaltrials.gov, NCT01752309. Registered on 19 December 2012.

Within the larger context of intertextuality in contemporary South African works of fiction, the article focuses on Michiel Heyns's novel, Invisible Furies, whose characters, plot trajectories, narrative strategies and thematic concerns are closely inscribed over those of Henry James's The Ambassadors. The article questions whether such blatant appropriation of a classic text might not risk becoming a form of self-marginalisation by the appropriating author, acknowledgement of the primacy of the source text and acceptance of an ancillary role. Approaching Heyns's novel from various theoretical perspectives on intertextuality and memory (Kristeva's intertextuality, Genette's hypertextuality, Riffaterre's obligatory intertextuality, Hutcheon's adaptation), the article examines Heyns's narrative performance in the margins of James's text in terms of Hutcheon's redefinition of intertextual parody as “repetition with critical distance that allows ironic signalling of difference at the very heart of similarity”, and concludes that in Invisible FuriesHeyns combines an impressive intertextual feat with an ironic interrogation of intertextuality itself.

Hereditary angioedema (HAE) causes recurrent, debilitating attacks. Prophylaxis with garadacimab (anti-activated factor XII monoclonal antibody) demonstrated efficacy with a favorable safety profile in double-blind Phase 2 and pivotal Phase 3 (VANGUARD) studies. We report results from an ongoing open-label extension (OLE) study (NCT04739059).

In the PATHWAY (NCT02054130) and NAVIGATOR (NCT03347279) studies, tezepelumab reduced exacerbations and improved lung function versus placebo in a broad population of patients with severe, uncontrolled asthma. This pooled analysis of PATHWAY and NAVIGATOR evaluated the effect of tezepelumab on biomarker levels and asthma symptoms in patients with allergic and eosinophilic asthma at baseline.

Here we describe the development and general characteristics of PIONEER-HAE, an enhanced database combining electronic medical data with insight from chart review, for the purpose of informing future studies.

This study was conducted to determine whether circulating concentrations of blood isoprostanes can be used as an effective biomarker in lambs to predict degradation of color and/or lipid stability in meat. Lambs (n= 84) were fed diets of either lucerne pasture, annual ryegrass pasture, a commercial feedlot pellet, or a combination of annual ryegrass and feedlot pellet for 8 wk, including a 2-wk adaptation period. Blood isoprostane concentration at wk 0, 4, 6 or 8 of feeding was determined. Blood isoprostane concentration for each animal was then correlated with muscle biochemical components that impact color and/or lipid oxidative status during retail display. This included lipid oxidation levels in muscle assessed by thiobarbituric acid reactive substances and meat redness determined by a HunterLab colorimetric spectrometer. Lambs that consumed the commercial feedlot pellet had a lower muscle vitamin E level (P< 0.01) and a greater level of n-6 PUFA (P< 0.001) compared with lambs finished on annual ryegrass or lucerne. Lipid oxidation levels were greatest for lambs finished on the feedlot ration, lowest in lambs finished on the ryegrass diet, and intermediate for lambs finished on lucerne and ryegrass–feedlot combination (P< 0.01). After 8 wk of feeding, blood isoprostane concentration was positively correlated with lipid oxidation of meat displayed for 72 h in simulated retail conditions (P< 0.01). There was a negative linear relationship between isoprostane concentration and muscle vitamin E concentration (P= 0.07), lipid oxidation and muscle vitamin E concentration (P< 0.01) but a positive linear relationship between isoprostane concentration and muscle n-6 PUFA (P< 0.001) or lipid oxidation and muscle n-6 PUFA concentration (P< 0.001). Blood isoprostane concentration and lipid oxidation in meat were influenced by muscle vitamin E and n-6 PUFA but not by n-3 PUFA. There was no significant relationship observed between blood isoprostane concentration at 0, 4, 6 or 8 wk feeding vs. overall meat color (redness of meat) at 0 and 72 h of display, stored under simulated retail conditions. The results indicate that circulating blood isoprostane concentration can be a useful tool to predict the oxidative status of postmortem meat. Future work will examine the impact of this relationship on meat flavor/aroma deterioration post farm.

Dead space is the portion of tidal volume that does not participate in alveolar gas exchange. The purpose of this study was to compare the dead space contribution of differently shaped masks, of the same size, by measuring the volume of each mask. The study was conducted in the Clinical Simulation Unit of the School of Medicine, University of the Free State (UFS) using formed masks with inflatable polyvinylchloride (PVC) cuffs and rounded masks with non-inflatable PVC cuffs. The masks were placed on the faces of the infant, child and adult part-task trainers as well as on a flat surface. The cuffs of the formed masks were inflated to 5 cm water and 70 cm water. Masks were filled with water and the volume was measured.The volumes (ml) of the masks on the flat surface were significantly larger than those measured on the part-task trainers’ faces. The volume of the rounded masks was greater than the volume of the formed masks. The amount of cuff inflation pressure (5 cm water vs. 70 cm water) did not lead to a significant change in mask volume: 102.3 ml (standard deviation [SD] 75.9) vs. 110.2 ml (SD 82.3), averaged for all sizes.Formed masks contribute less to anatomical dead space than rounded masks and are thus possibly the better choice. Cuff inflation pressure has insignificant influence on dead space volume.

Recently, the use of metal-on-metal articulations in total hip arthroplasty (THA) has led to an increase in adverse events owing to local soft-tissue reactions from metal ions and wear debris. While the majority of these implants perform well, it has been increasingly recognised that a small proportion of patients may develop complications secondary to systemic cobalt toxicity when these implants fail. However, distinguishing true toxicity from benign elevations in cobalt ion levels can be challenging. The purpose of this two part series is to review the use of cobalt alloys in THA and to highlight the following related topics of interest: mechanisms of cobalt ion release and their measurement, definitions of pathological cobalt ion levels, and the pathophysiology, risk factors and treatment of cobalt toxicity. Historically, these metal-on-metal arthroplasties are composed of a chromium-cobalt articulation. The release of cobalt is due to the mechanical and oxidative stresses placed on the prosthetic joint. It exerts its pathological effects through direct cellular toxicity. This manuscript will highlight the pathophysiology of cobalt toxicity in patients with metal-on-metal hip arthroplasties.Take home message: Patients with new or evolving hip symptoms with a prior history of THA warrant orthopaedic surgical evaluation. Increased awareness of the range of systemic symptoms associated with cobalt toxicity, coupled with prompt orthopaedic intervention, may forestall the development of further complications.Cite this article: Bone Joint J2016;98-B:6–13.

As adverse events related to metal on metal hip arthroplasty have been better understood, there has been increased interest in toxicity related to the high circulating levels of cobalt ions. However, distinguishing true toxicity from benign elevations in cobalt levels can be challenging. The purpose of this review is to examine the use of cobalt alloys in total hip arthroplasty, to review the methods of measuring circulating cobalt levels, to define a level of cobalt which is considered pathological and to review the pathophysiology, risk factors and treatment of cobalt toxicity. To the best of our knowledge, there are 18 published cases where cobalt metal ion toxicity has been attributed to the use of cobalt-chromium alloys in hip arthroplasty. Of these cases, the great majority reported systemic toxic reactions at serum cobalt levels more than 100 μg/L. This review highlights some of the clinical features of cobalt toxicity, with the goal that early awareness may decrease the risk factors for the development of cobalt toxicity and/or reduce its severity.Take home message: Severe adverse events can arise from the release of cobalt from metal-on-metal arthroplasties, and as such, orthopaedic surgeons should not only be aware of the presenting problems, but also have the knowledge to treat appropriately.Cite this article: Bone Joint J2016;98-B:14–20.

The continual cycle of bone formation and resorption is carried out by osteoblasts, osteocytes, and osteoclasts under the direction of the bone-signaling pathway. In certain situations the host cycle of bone repair is insufficient and requires the assistance of bone grafts and their substitutes. The fundamental properties of a bone graft are osteoconduction, osteoinduction, osteogenesis, and structural support. Options for bone grafting include autogenous and allograft bone and the various isolated or combined substitutes of calcium sulphate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. Not all bone grafts will have the same properties. As a result, understanding the requirements of the clinical situation and specific properties of the various types of bone grafts is necessary to identify the ideal graft. We present a review of the bone repair process and properties of bone grafts and their substitutes to help guide the clinician in the decision making process.Cite this article: Bone Joint J2016;98-B(1 Suppl A):6–9.

Microlaena stipoides (microlaena) is an important perennial grass in over 7million hectares of native pastures in southern Australia and can survive and persist despite severe soil water deficits during summer. Many other pasture species survive similar conditions by relying on summer dormancy, which raises the possibility that microlaena may behave similarly. A field experiment using rainout shelters was conducted on an existing microlaena pasture in north-east Victoria. The experiment was a split-plot design with two watering treatments (‘summer storm’ or ‘summer dry’) as main plots and three defoliation treatments (nil, intense defoliation, strategic defoliation) as subplots. The ‘summer storm’ treatment resulted in the formation of new buds and tillers and increased basal cover from 1% in February to 18% in March. A glasshouse pot experiment examined the recovery of microlaena after different periods of drought and subsequent rewatering. In the pot experiment, microlaena withstood relatively short (up to 30 days) dry periods and then recovered when rewatered. Thus, it appears that microlaena is a persistent, perennial pasture plant that, although it survives very dry summers in Mediterranean areas, is not summer dormant. Microlaena does not exhibit summer dormancy in response to moisture stress and enter a quiescent stage, because normal growth is prevented by the lack of water, but it quickly recommences growth when soil water becomes available. The ability of microlaena to withstand summer soil water deficits and to recruit from seedlings make it a valuable pasture species across drought-prone environments, and this undoubtedly partly explains its very broad adaptation across eastern Australia.