Search Results (32)

This article reconsiders literature’s capacity to express and evoke spiritual experiences by turning to William James’s The Varieties of Religious Experience, especially his discussion of mysticism and his suggestion that poetry can bring about such states. James’s ideas are especially promising given recent developments in postsecular and postcritical scholarship that problematize a religious/secular divide and call into question a hermeneutics of suspicion. Bringing James into conversation with Paul Ricoeur, I aim to show how receptivity to spiritual experiences in literature might generate expansive models of both poetics and hermeneutics. To pursue these possibilities, my study analyzes three examples of Victorian lyric poems that probe the edges of wonder: Thomas Hardy’s “The Darkling Thrush”, Gerard Manley Hopkins’s “Nondum” and Dollie Radford’s “A Dream of ‘Dreams’”. These case studies strategically select work by writers of various belief or unbelief positions, highlighting the dynamism of the late nineteenth-century moment from which James’s writings emerged. I argue that this poetry facilitates a re-imagination of hope, beyond a faith/doubt dichotomy, as well as a re-framing of revelation, from proclamation to invitation. Building on insights from both James and Ricoeur, my discussion concludes by making the case for cultivating an interpretive disposition that does not guard against but opens toward poetry’s latent potential to take readers by surprise. Full article

Introduction: Arthroscopic Bankart repair (ABR) is associated with an increased failure rate over time. The Recenter implant, a metal block, is designed to reinforce capsulolabral repair. The aim of this study was to evaluate whether the addition of the Recenter implant to ABR reduces the rate of recurrence in patients with glenohumeral anterior instability. Materials and Methods: This was a retrospective, multicentric case–control study focusing on patients surgically treated for anterior shoulder instability from February 2012 to November 2019. This study compared patients undergoing ABR augmented with the “Recenter” implant (augmented ABR group) against those receiving traditional ABR. Primary outcomes measured included recurrence rates. Secondary outcome measures included functional scores (Walch–Duplay and the subjective shoulder test [SST], the auto Rowe score, satisfaction, pain, and the presence or absence of subjective subluxation and apprehension), return to sports, the range of motion, as well as other complications. Results: Thirty-two patients with augmented ABR were compared to forty-eight patients in the traditional ABR group, with mean follow-up periods of 5.2 ± 1.3 years and 6.1 ± 1.5 years, respectively. Three patients (9.4%) experienced recurrence in the “Recenter” group, versus eight (16.7%) in the other group (p > 0.05). The Walch–Duplay score was 70.2 ± 8.2 in the “Recenter” group and 64.2 ± 8 in the control group (p > 0.05). The SST score out of 100 was, respectively, 84.6 ± 6 and 81.5 ± 5.5 (p = 0.05). There were no early complications in the implant group. No statistically significant differences were observed between the two groups for the other outcomes. Conclusions: ABR safely restores shoulder stability in selected patients with subcritical glenoid bone deficiency. However, the addition of the Recenter metal implant did not improve outcomes compared to traditional Bankart repair and introduced presumed significant surgical time, technical challenges, and additional costs. Full article

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause autosomal dominant Parkinson’s disease (PD), with the most common causative mutation being the LRRK2 p.G2019S within the kinase domain. LRRK2 protein is highly expressed in the human brain and also in the periphery, and high expression of dominant PD genes in immune cells suggests involvement of microglia and macrophages in inflammation related to PD. LRRK2 is known to respond to extracellular signalling including TLR4, resulting in alterations in gene expression, with the response to TLR2 signalling through zymosan being less known. Here, we investigated the effects of zymosan, a TLR2 agonist and the potent and specific LRRK2 kinase inhibitor MLi-2 on gene expression in microglia from LRRK2-WT and LRRK2 p.G2019S knock-in mice by RNA-sequencing analysis. We observed both overlapping and distinct zymosan and MLi-2 mediated gene expression profiles in microglia. At least two candidate genome-wide association (GWAS) hits for PD, CathepsinB (Ctsb) and Glycoprotein-nmb (Gpnmb), were notably downregulated by zymosan treatment. Genes involved in inflammatory response and nervous system development were up and downregulated, respectively, with zymosan treatment, while MLi-2 treatment particularly exhibited upregulated genes for ion transmembrane transport regulation. Furthermore, we observed that the top twenty most significantly differentially expressed genes in LRRK2 p.G2019S microglia show enriched biological processes in iron transport and response to oxidative stress. Overall, these results suggest that microglial LRRK2 may contribute to PD pathogenesis through altered inflammatory pathways. Our findings should encourage future investigations of these putative avenues in the context of PD pathogenesis. Full article

A significant genetic involvement has been known for decades to exist in adolescent idiopathic scoliosis (AIS), a spine deformity affecting 1–3% of the world population. However, though biomechanical and endocrinological theories have emerged, no clear pathophysiological explanation has been found. Data from the whole-exome sequencing performed on 113 individuals in 19 multi-generational families with AIS have been filtered and analyzed via interaction pathways and functional category analysis (Varaft, Bingo and Panther). The subsequent list of 2566 variants has been compared to the variants already described in the literature, with an 18% match rate. The familial analysis in two families reveals mutations in the BICD2 gene, supporting the involvement of the muscular system in AIS etiology. The cellular component analysis revealed significant enrichment in myosin-related and neuronal activity-related categories. All together, these results reinforce the suspected role of the neuronal and muscular systems, highlighting the calmodulin pathway and suggesting a role of DNA-binding activities in AIS physiopathology. Full article

One reason why the concept of the quotidian has proved elusive to critics of literature and the visual arts is that the commonplace in art and literature so often refuses to remain untransfigured, not least because of its power to confront us with the material detritus with which we surround ourselves and which we will eventually join. It is not surprising, then, that contemporary artists share a preoccupation with finding both mortality and transcendence in what John Wilmot, Earl of Rochester called “the lumber of the world.” In this paper, I shall consider how an early Damien Hirst mini-installation, consisting of a glass tumbler of water and a ping-pong ball, takes its only partly mocking place in a still life tradition going back to Roman xenia and seventeenth-century vanitas paintings, and to a related literary tradition typified by Thomas Hardy’s Under the Waterfall and James Joyce’s great prose aria to water all its forms in the Ithaca section of Ulysses. Full article

We developed a floodplain inundation model to extract specific flood extent and depth parameters and combined these with vegetation land cover and historic flow data to quantify spatial habitat suitability and temporal hydrologic metrics that support Alligator Gar Atractosteus spatula spawning within a 257 km segment of the lower Guadalupe River, Texas, USA. We modeled nine flows across a range of flood frequency recurrence intervals from 257 m³s⁻¹ to ~4997 m³s⁻¹ and estimated the availability of suitable spawning water depths (0.2 to 2 m) and lateral connectedness between the river and suitable floodplain landcover types. We estimated the ages via otoliths of 95 Alligator Gar collected in the reach to determine the year that they were recruited into the system. We analyzed a total of 30 Indicators of Hydrologic Alteration flow metrics to examine how the spatially derived suitable habitats related to the temporal aspects of flow occurrence during the spawning season for the period of flow record April–July (1935–2020) and to the years spanning the recruitment data of the Alligator Gar (1981–2010). A non-linear relationship existed between suitable spawning habitat area and the flow regime, with the most habitat availability corresponding to the 10–20-year flood recurrence interval frequency with peak flows of 2057–3108 m³s⁻¹, respectively. The Alligator Gar recruitment data indicated that six years provided high recruitment, which correlated with peak flows of ~5-year frequency with an available spawning area of ~9000 Ha, moderate recruitment years related to peak flows with ~3-year frequency with an available spawning area of 6000 Ha, and low recruitment years where spawning was likely to occur at least every other year with at least 2500 Ha of available spawning area. The results of this model support the development of legislatively mandated environmental flow standards for the Guadalupe River Basin, inform field-based efforts for collecting empirical and observational data on the species’ reproduction, and provide spatial and temporal information for designing conservation strategies for Alligator Gar. Full article

Tedera is a valuable high-quality forage for sheep during summer–autumn. There is evidence that prior grazing experience of novel forages influences preference and haymaking of tedera improves preference by goats. In the first experiment, it was hypothesised that the voluntary feed intake (VFI) of fresh leaves and stems of tedera by sheep would be greater for experienced vs. naïve sheep. In the second experiment, it was hypothesised that the VFI of naïve sheep fed wilted leaves and stems of tedera would be greater than fresh leaves and stems of tedera. To test these hypotheses, adult Merino sheep were fed seven accessions of tedera, in two outdoor pen feeding experiments conducted consecutively. Each of six pens had 14 feeders, two for each accession, and two sheep. In experiment 1, three pens had sheep that had previously grazed tedera (experienced) and three pens had sheep with no experience (naïve), and all were fed fresh leaves and stems of the seven tedera accessions. Experiment 2 involved only naïve sheep, with three pens fed fresh leaves and stems and three pens fed wilted leaves and stems of the seven tedera accessions. Preference was measured each day for six days in experiment 1; and for five days in experiment 2 by calculating the average differences of feed offered and feed remaining from the feeders. In experiment 1, experienced sheep showed no difference in preference (average percentage eaten) in the first hour of each day compared to naïve sheep (70% vs. 56% DM intake (kg), p = 0.27). There was an increase in the amount eaten from the first to the last day for both groups, except for the intake of one accession that was reduced for the experienced sheep. In experiment 2, there was no statistical difference in preference between accessions. However, when the average percentage eaten by the experienced and naïve groups are combined, they are strongly correlated, with significant differences between accessions. Sheep did not eat more wilted tedera compared to fresh, which did not support our hypothesis. The only differences we found in sheep preference for tedera accessions occurred in experiment 1. Further studies to investigate seasonal differences in sheep preference between accessions is required and increased replication is needed to better determine the effect of prior grazing experience on the preference for tedera accessions. Full article

Age-related disorders of the musculoskeletal system including sarcopenia, osteoporosis and arthritis represent some of the most common chronic conditions worldwide, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. Collectively, these conditions involve multiple tissues, including skeletal muscle, bone, articular cartilage and the synovium within the joint lining. In this review, we discuss the potential for oligonucleotide therapies to combat the unmet clinical need in musculoskeletal disorders by evaluating the successes of oligonucleotides to modify candidate pathological gene targets and cellular processes in relevant tissues and cells of the musculoskeletal system. Further, we discuss the challenges that remain for the clinical development of oligonucleotides therapies for musculoskeletal disorders and evaluate some of the current approaches to overcome these. Full article

D-dimer is a multifaceted biomarker of concomitant activation of coagulation and fibrinolysis, which is routinely used for ruling out pulmonary embolism (PE) and/or deep vein thrombosis (DVT) combined with a clinical pretest probability assessment. The intended use of the tests depends largely on the assay used, and local guidance should be applied. D-dimer testing may suffer from diagnostic errors occurring throughout the pre-analytical, analytical, and post-analytical phases of the testing process. This review aims to provide an overview of D-dimer testing and its value in diagnosing PE and discusses the variables that may impact the quality of its laboratory assessment. Full article

Easy and robust antimicrobial susceptibility testing (AST) methods are essential in clinical bacteriology laboratories (CBL) in low-resource settings (LRS). We evaluated the Beckman Coulter MicroScan lyophilized broth microdilution panel designed to support Médecins Sans Frontières (MSF) CBL activity in difficult settings, in particular with the Mini-Lab. We evaluated the custom-designed MSF MicroScan Gram-pos microplate (MICPOS1) for Staphylococcus and Enterococcus species, MSF MicroScan Gram-neg microplate (MICNEG1) for Gram-negative bacilli, and MSF MicroScan Fastidious microplate (MICFAST1) for Streptococci and Haemophilus species using 387 isolates from routine CBLs from LRS against the reference methods. Results showed that, for all selected antibiotics on the three panels, the proportion of the category agreement was above 90% and the proportion of major and very major errors was below 3%, as per ISO standards. The use of the Prompt inoculation system was found to increase the MIC and the major error rate for some antibiotics when testing Staphylococci. The readability of the manufacturer’s user manual was considered challenging for low-skilled staff. The inoculations and readings of the panels were estimated as easy to use. In conclusion, the three MSF MicroScan MIC panels performed well against clinical isolates from LRS and provided a convenient, robust, and standardized AST method for use in CBL in LRS. Full article

Long-term observation of Earth’s temporal gravity field with enhanced temporal and spatial resolution is a major objective for future satellite gravity missions. Improving the performance of the accelerometers present in such missions is one of the main paths to explore. In this context, we propose to study an original concept of a hybrid accelerometer associating a state-of-the-art electrostatic accelerometer (EA) and a promising quantum sensor based on cold atom interferometry. To assess the performance potential of such an instrument, numerical simulations were performed to determine its impact in terms of gravity field retrieval. Taking advantage of the long-term stability of the cold atom interferometer (CAI), it is shown that the reduced drift of the hybrid sensor could lead to improved gravity field retrieval. Nevertheless, this gain vanishes once temporal variations of the gravity field and related aliasing effects are taken into account. Improved de-aliasing models or some specific satellite constellations are then required to maximize the impact of the accelerometer performance gain. To evaluate the achievable acceleration performance in-orbit, a numerical simulator of the hybrid accelerometer was developed and preliminary results are given. The instrument simulator was in part validated by reproducing the performance achieved with a hybrid lab prototype operating on the ground. The problem of satellite rotation impact on the CAI was also investigated both with instrument performance simulations and experimental demonstrations. It is shown that the proposed configuration, where the EA’s proof-mass acts as the reference mirror for the CAI, seems a promising approach to allow the mitigation of satellite rotation. To evaluate the feasibility of such an instrument for space applications, a preliminary design is elaborated along with a preliminary error, mass, volume, and electrical power consumption budget. Full article

This work investigates and compares the fatigue performance of laser-welded joints of two press hardening steels: a standard 22MnB5 and a variant modified by a combination of niobium and molybdenum (NbMo) alloying. The results indicate that joint geometry aspects, superposed to an intrusion-generated damage mechanism, were prevalent in causing a poor fatigue life in the case of peak stress values greater than 11% of the base metal's ultimate strength being around 1450 MPa. As identical process procedures were employed, the tests allowed investigating the influence of the alloy design on fatigue performance. The results of geometrical analysis and fatigue tests indicated that the NbMo modified alloy performed better than the standard 22MnB5 steel. The results also suggest that, if extremely tight quality limits are used in the manufacturing procedures, laser-welded joints of press hardened steels could offer a very favorable fatigue performance being considerably better than that of conventional and high strength structural steels. Full article

Continuous intravenous unfractionated heparin (UFH) is administered routinely in the intensive care unit (ICU) for the anticoagulation of patients, and monitoring is performed by the activated partial thromboplastin time (APTT) or anti-Xa activity. However, these strategies are associated with potentially large time intervals before dose adjustments, which could be detrimental to the patient. The aim of the study was to compare a point-of-care (POCT) version of the APTT to (i) laboratory-based APTT and (ii) measurements of anti-Xa activity in terms of correlation, agreement and turnaround time (TAT). Thirty-five ICU patients requiring UFH therapy were prospectively included and followed longitudinally for a maximum duration of 15 days. UFH was administered according to a local adaptation of Raschke and Amanzadeh’s aPTT nomograms. Simultaneous measurements of POCT-APTT (CoaguCheck^® aPTT Test, Roche Diagnostics) on a drop of fresh whole blood, laboratory-based APTT (C.K. Prest^®, Stago) and anti-Xa activity (STA^®Liquid anti-Xa, Stago) were systematically performed two to six times a day. Antithrombin, C-reactive protein, fibrinogen, factor VIII and lupus anticoagulant were measured. The time tracking of sampling and analysis was recorded. The overall correlation between POCT-APTT and laboratory APTT (n = 795 pairs) was strongly positive (rs = 0.77, p < 0.0001), and between POCT-APTT and anti-Xa activity (n = 729 pairs) was weakly positive (rs = 0.46, p < 0.0001). Inter-method agreement (Cohen’s kappa (k)) between POCT and laboratory APTT was 0.27, and between POCT and anti-Xa activity was 0.30. The median TATs from sample collection to the lab delivery of results for lab-APTT and anti-Xa were 50.9 min (interquartile range (IQR), 38.4–69.1) and 66.3 min (IQR, 49.0–91.8), respectively, while the POCT delivered results in less than 5 min (p < 0.0001). Although the use of the POCT-APTT device significantly reduced the time to results, the results obtained were poorly consistent with those obtained by lab-APTT or anti-Xa activity, and therefore it should not be used with the nomograms developed for lab-APTT. Full article

Microglial exosomes are an emerging communication pathway, implicated in fulfilling homeostatic microglial functions and transmitting neurodegenerative signals. Gene variants of triggering receptor expressed on myeloid cells-2 (TREM2) are associated with an increased risk of developing dementia. We investigated the influence of the TREM2 Alzheimer’s disease risk variant, R47H^het, on the microglial exosomal proteome consisting of 3019 proteins secreted from human iPS-derived microglia (iPS-Mg). Exosomal protein content changed according to how the iPS-Mg were stimulated. Thus lipopolysaccharide (LPS) induced microglial exosomes to contain more inflammatory signals, whilst stimulation with the TREM2 ligand phosphatidylserine (PS⁺) increased metabolic signals within the microglial exosomes. We tested the effect of these exosomes on neurons and found that the exosomal protein changes were functionally relevant and influenced downstream functions in both neurons and microglia. Exosomes from R47H^het iPS-Mg contained disease-associated microglial (DAM) signature proteins and were less able to promote the outgrowth of neuronal processes and increase mitochondrial metabolism in neurons compared with exosomes from the common TREM2 variant iPS-Mg. Taken together, these data highlight the importance of microglial exosomes in fulfilling microglial functions. Additionally, variations in the exosomal proteome influenced by the R47H^het TREM2 variant may underlie the increased risk of Alzheimer’s disease associated with this variant. Full article

Postnatal corticosteroids improve respiratory status and facilitate respiratory support weaning in preterm infants with bronchopulmonary dysplasia (BPD). Older literature describes characteristic cytokine profiles in tracheal aspirates (TA) of BPD patients which are altered with corticosteroids. Corticosteroids also influence peripheral blood T-cell presence. However, little is known regarding TA T-cell phenotype and cytokine production before or after exogenous corticosteroids. We hypothesized that postnatal dexamethasone alters the TA T-cell cytokine profiles of preterm infants. TA samples were collected from 14 infants born from 23 0/7 to 28 6/7 weeks who were mechanically ventilated for at least 14 days. Samples were collected up to 72 h before a ten-day dexamethasone course and again 1 to 3 calendar days after dexamethasone initiation. The primary outcome was change in T cell populations present in TA and their intracellular cytokine profile after dexamethasone treatment, ascertained via flow cytometry. Following dexamethasone treatment, there were significant decreases in respiratory severity score (RSS), percent CD4+IL-6+ cells, CD8+IL-6+ cells, CXCR3+IL-6+ cells, and CXCR3+IL-2+ cells and total intracellular IFN-γ in TA. RSS significantly correlated with TA percent CD4+IL-6+ cells. To our knowledge, this is the first study demonstrating that dexamethasone reduced T-cell IL-6 and this reduction was associated with improved RSS in pre-term infants with evolving BPD. Full article