Load transfer in bone after partial, multi-compartmental, and total knee arthroplasty

Introduction: Arthroplasty-associated bone loss remains a clinical problem: stiff metallic implants disrupt load transfer to bone and, hence, its remodeling stimulus. The aim of this research was to analyze how load transfer to bone is affected by different forms of knee arthroplasty: isolated partial knee arthroplasty (PKA), compartmental arthroplasty [combined partial knee arthroplasty (CPKA), two or more PKAs in the same knee], and total knee arthroplasty (TKA).Methods: An experimentally validated subject-specific finite element model was analyzed native and with medial unicondylar, lateral unicondylar, patellofemoral, bi-unicondylar, medial bicompartmental, lateral bicompartmental, tricompartmental, and total knee arthroplasty. Three load cases were simulated for each: gait, stair ascent, and sit-to-stand. Strain shielding and overstraining were calculated from the differences between the native and implanted states.Results: For gait, the TKA femoral component led to mean strain shielding (30%) more than three times higher than that of PKA (4%–7%) and CPKA (5%–8%). Overstraining was predicted in the proximal tibia (TKA 21%; PKA/CPKA 0%–6%). The variance in the distribution for TKA was an order of magnitude greater than for PKA/CPKA, indicating less physiological load transfer. Only the TKA-implanted femur was sensitive to the load case: for stair ascent and gait, almost the entire distal femur was strain-shielded, whereas during sit-to-stand, the posterior femoral condyles were overstrained.Discussion: TKA requires more bone resection than PKA and CPKA. These finite element analyses suggest that a longer-term benefit for bone is probable as partial and multi-compartmental knee procedures lead to more natural load transfer compared to TKA. High-flexion activity following TKA may be protective of posterior condyle bone resorption, which may help explain why bone loss affects some patients more than others. The male and female bone models used for this research are provided open access to facilitate future research elsewhere

Changing impacts of Alaska-Aleutian subduction zone tsunamis in California under future sea-level rise

The amplification of coastal hazards such as distant-source tsunamis under future relative sea-level rise (RSLR) is poorly constrained. In southern California, the Alaska-Aleutian subduction zone has been identified as an earthquake source region of particular concern for a worst-case scenario distant-source tsunami. Here, we explore how RSLR over the next century will influence future maximum nearshore tsunami heights (MNTH) at the Ports of Los Angeles and Long Beach. Earthquake and tsunami modeling combined with local probabilistic RSLR projections show the increased potential for more frequent, relatively low magnitude earthquakes to produce distant-source tsunamis that exceed historically observed MNTH. By 2100, under RSLR projections for a high-emissions representative concentration pathway (RCP8.5), the earthquake magnitude required to produce \u3e1 m MNTH falls from ~Mw9.1 (required today) to Mw8.0, a magnitude that is ~6.7 times more frequent along the Alaska-Aleutian subduction zone

Understanding the small object argument

The small object argument is a transfinite construction which, starting from a set of maps in a category, generates a weak factorisation system on that category. As useful as it is, the small object argument has some problematic aspects: it possesses no universal property; it does not converge; and it does not seem to be related to other transfinite constructions occurring in categorical algebra. In this paper, we give an "algebraic" refinement of the small object argument, cast in terms of Grandis and Tholen's natural weak factorisation systems, which rectifies each of these three deficiencies.Comment: 42 pages; supersedes the earlier arXiv preprint math/0702290; v2: final journal version, minor corrections onl

Enhanced insulin receptor, but not PI3K, signalling protects podocytes from ER stress

Abstract Disruption of the insulin-PI3K-Akt signalling pathway in kidney podocytes causes endoplasmic reticulum (ER) stress, leading to podocyte apoptosis and proteinuria in diabetic nephropathy. We hypothesised that by improving insulin sensitivity we could protect podocytes from ER stress. Here we use established activating transcription factor 6 (ATF6)- and ER stress element (ERSE)-luciferase assays alongside a novel high throughput imaging-based C/EBP homologous protein (CHOP) assay to examine three models of improved insulin sensitivity. We find that by improving insulin sensitivity at the level of the insulin receptor (IR), either by IR over-expression or by knocking down the negative regulator of IR activity, protein tyrosine-phosphatase 1B (PTP1B), podocytes are protected from ER stress caused by fatty acids or diabetic media containing high glucose, high insulin and inflammatory cytokines TNFα and IL-6. However, contrary to this, knockdown of the negative regulator of PI3K-Akt signalling, phosphatase and tensin homolog deleted from chromosome 10 (PTEN), sensitizes podocytes to ER stress and apoptosis, despite increasing Akt phosphorylation. This indicates that protection from ER stress is conferred through not just the PI3K-Akt pathway, and indeed we find that inhibiting the MEK/ERK signalling pathway rescues PTEN knockdown podocytes from ER stress

Plasma Dynamics

Contains reports on six research projects.National Science Foundation (Grant ENG79-07047)U.S. Air Force - Office of Scientific Research (Grant AFOSR77-3143D)U.S. Air Force - Office of Scientific Research (Contract AFOSR82-0063)U.S. Department of Energy (Contract DE-ACO2-78-ET-51013)U.S. Department of Energy (Contract DE-AC02-78ET-53073.A002

Effect of Zephyr Endobronchial Valves on Dyspnea, Activity Levels, and Quality of Life at One Year Results from a Randomized Clinical Trial

Rationale: Bronchoscopic lung volume reduction with Zephyr Valves improves lung function, exercise tolerance, and quality of life of patients with hyperinflated emphysema and little to no collateral ventilation. Objectives: Post hoc analysis of patient-reported outcomes (PROs), including multidimensional measures of dyspnea, activity, and quality of life, in the LIBERATE (Lung Function Improvement after Bronchoscopic Lung Volume Reduction with Pulmonx Endobronchial Valves used in Treatment of Emphysema) study are reported. Methods: A total of 190 patients with severe heterogeneous emphysema and little to no collateral ventilation in the target lobe were randomized 2:1 to the Zephyr Valve or standard of care. Changes in PROs at 12 months in the two groups were compared: dyspnea with the Transitional Dyspnea Index (TDI), focal score; the Chronic Obstructive Pulmonary Disease Assessment Test (CAT; breathlessness on hill/stairs); Borg; the EXAcerbations of Chronic pulmonary disease Tool-PRO, dyspnea domain; activity with the TDI, magnitude of task/effort/functional impairment, CAT (limited activities), and the St. George's Respiratory Questionnaire (SGRQ), activity domain; and psychosocial status with the SGRQ, impacts domain, and CAT (confidence and energy). Results: At 12 months, patients using the Zephyr Valve achieved statistically significant and clinically meaningful improvements in the SGRQ; CAT; and the TDI, focal score, compared with standard of care. Improvements in the SGRQ were driven by the impacts and activity domains (P, 0.05 and P, 0.001, respectively). Reduction in CAT was through improvements in breathlessness (P, 0.05), energy level (P, 0.05), activities (P, 0.001), and increased confidence when leaving home (P, 0.05). The TDI measures of effort, task, and functional impairment were uniformly improved (P, 0.001). The EXAcerbations of Chronic Pulmonary Disease Tool (EXACT)-PRO, dyspnea domain, was significantly improved in the Zephyr Valve group. Improvements correlated with changes in residual volume and residual volume/TLC ratio. Conclusions: Patients with severe hyperinflated emphysema achieving lung volume reductions with Zephyr Valves experience improvements in multidimensional scores for breathlessness, activity, and psychosocial parameters out to at least 12 months

The transcription factor NR4A1 is essential for the development of a novel macrophage subset in the thymus

Tissue macrophages function to maintain homeostasis and regulate immune responses. While tissue macrophages derive from one of a small number of progenitor programs, the transcriptional requirements for site-specific macrophage subset development are more complex. We have identified a new tissue macrophage subset in the thymus and have discovered that its development is dependent on transcription factor NR4A1. Functionally, we find that NR4A1-dependent macrophages are critically important for clearance of apoptotic thymocytes. These macrophages are largely reduced or absent in mice lacking NR4A1, and Nr4a1-deficient mice have impaired thymocyte engulfment and clearance. Thus, NR4A1 functions as a master transcription factor for the development of this novel thymus-specific macrophage subset

Stereochemical Insignificance Discovered in Acinetobacter baumannii Quorum Sensing

Stereochemistry is a key aspect of molecular recognition for biological systems. As such, receptors and enzymes are often highly stereospecific, only recognizing one stereoisomer of a ligand. Recently, the quorum sensing signaling molecules used by the nosocomial opportunistic pathogen, Acinetobacter baumannii, were identified, and the primary signaling molecule isolated from this species was N-(3-hydroxydodecanoyl)-l-homoserine lactone. A plethora of bacterial species have been demonstrated to utilize 3-hydroxy-acylhomoserine lactone autoinducers, and in virtually all cases, the (R)-stereoisomer was identified as the natural ligand and exhibited greater autoinducer activity than the corresponding (S)-stereoisomer. Using chemical synthesis and biochemical assays, we have uncovered a case of stereochemical insignificance in A. baumannii and provide a unique example where stereochemistry appears nonessential for acylhomoserine lactone-mediated quorum sensing signaling. Based on previously reported phylogenetic studies, we suggest that A. baumannii has evolutionarily adopted this unique, yet promiscuous quorum sensing system to ensure its survival, particularly in the presence of other proteobacteria

Multiple introductions and human-aided dispersal of the UK’s most widespread non-native amphibian

The alpine newt Ichthyosaura alpestris has achieved a widespread distribution as a non-native (alien) species in Britain since its initial introduction over a century ago, but the patterns of its release and subsequent dispersal have never yet been collectively analysed. We employed a multi-disciplinary combination of methods, using geographic profiling to estimate the likely number and locations of introductions, and mitochondrial DNA polymorphisms to investigate the likely geographic source of primary introductions, including the potential role of the pet trade. In parallel we used population genetic analysis and coalescence-based modelling to infer the demographics and directionality of dispersal from founding populations. Our results show that alpine newts have been released at multiple sites. We found a close resemblance between patterns of mtDNA haplotypes in the pet trade and those of established alpine newt populations, suggesting a relationship between trade, releases, and dispersal. Results from demographic modelling using Approximate Bayesian Computation are also consistent with multiple independent introductions with limited local dispersal, and additionally suggest that releases may occur from intermediate sources, such as captive populations. Our results support the hypothesis that deliberate human activity is largely responsible for both introductions of alpine newts into the UK and their wider dispersal post-introduction. The likely involvement of the international pet trade highlights the risk that ongoing releases of I. alpestris may expose native species to pathogens, whether pre-existing or novel

Ageing, Temporality and Performance: Joan Rivers’ Body of Work

Joan Rivers’ performance in the public sphere revolved around the visibility and cultural inscription of an ageing and older woman. Linking aesthetic, professional and physiological processes, her body, work and performance merged as and in an extended and finite professional practice. A pioneer of stand-up comedy as a genre, and one of its most significant and visible female practitioners, Rivers is known for her aggressive and often outrageous wit, which was directed at both herself and other celebrities, as well as her extensive plastic surgeries. When she died in 2014, at the age of 81, she was still fully engaged in a relentless schedule of live performances and televised appearances. By then, Rivers was well established as an ubiquitously present elder who refused to conform to long-standing stereotypes of asexuality, able to thrive in a rapidly shifting cultural landscape of surgically enhanced bodies, surveillance as entertainment and public confession. At the heart of the discussion in this article is the spatio-temporality of the performing body, borrowing from Maurice Merleau-Ponty’s understanding of the body as a “nexus of living meanings” and Jacques Derrida’s development of Merleau-Ponty’s use of the term “invagination” to embrace generic textual strategy. In stand-up as a genre, both originality and continuity are paradoxically valued by audiences in equal measure. Success – that is, laughter – is largely determined by the extent to which these align coherently with the comedian’s bodily presence and her onstage social, cultural and/or political positioning. Focusing primarily on the expression of Rivers’ persona via a variety of mutually reinforcing cultural texts in the final three years of her life, this article analyses how her performing body in every medium was importantly always made present through its sexual difference and attendant gendered ageing processes