"Not an idle spectator": Geoffrey Hill as model reviewer

Geoffrey Hill’s prose has prompted longstanding critical controversy, much of which turns on the perceived difficulty, intransigence and anachronism of his oeuvre as a whole. This paper proposes that new ways to navigate this controversy can be found in Hill’s preoccupation with the exemplary dimensions of writing – that is, in his interest in the poet’s capacity to offer examples (positive and negative) to a community of readers. The discussion pays particular attention to the connections Hill’s reviews establish between style and ethical choice and between literary difficulty and democracy; connections which are intertwined with his ethics of exemplarity in fundamental ways. The paper also engages with those dimensions of literary exemple-use which emerge in new or unusual ways in his prose: his presentation of ‘models’ or ideals for the organisation of civil society; his treatment of certain literary works as exemplars or embodiments of philosophical ideas; and his procedural tic of ‘sampling’ regularly for the purpose of chastisement the ‘bad example’ set by some of the works he criticises

Osteoarthritis accelerates and exacerbates Alzheimer's disease pathology in mice

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to investigate whether localized peripheral inflammation, such as osteoarthritis, contributes to neuroinflammation and neurodegenerative disease <it>in vivo</it>.</p> <p>Methods</p> <p>We employed the inducible Col1-IL1β^XATmouse model of osteoarthritis, in which induction of osteoarthritis in the knees and temporomandibular joints resulted in astrocyte and microglial activation in the brain, accompanied by upregulation of inflammation-related gene expression. The biological significance of the link between peripheral and brain inflammation was explored in the APP/PS1 mouse model of Alzheimer's disease (AD) whereby osteoarthritis resulted in neuroinflammation as well as exacerbation and acceleration of AD pathology.</p> <p>Results</p> <p>Induction of osteoarthritis exacerbated and accelerated the development of neuroinflammation, as assessed by glial cell activation and quantification of inflammation-related mRNAs, as well as Aβ pathology, assessed by the number and size of amyloid plaques, in the APP/PS1; Col1-IL1β^XATcompound transgenic mouse.</p> <p>Conclusion</p> <p>This work supports a model by which peripheral inflammation triggers the development of neuroinflammation and subsequently the induction of AD pathology. Better understanding of the link between peripheral localized inflammation, whether in the form of osteoarthritis, atherosclerosis or other conditions, and brain inflammation, may prove critical to our understanding of the pathophysiology of disorders such as Alzheimer's, Parkinson's and other neurodegenerative diseases.</p

Complete breeding failures in ivory gull following unusual rainy storms in North Greenland

Natural catastrophic events such as heavy rainfall and windstorms may induce drastic decreases in breeding success of animal populations. We report the impacts of summer rainfalls on the reproductive success of ivory gull (Pagophila eburnea) in north-east Greenland. On two occasions, at Amdrup Land in July 2009 and at Station Nord in July 2011, we observed massive ivory gull breeding failures following violent rainfall and windstorms that hit the colonies. In each colony, all of the breeding birds abandoned their eggs or chicks during the storm. Juvenile mortality was close to 100% at Amdrup Land in 2009 and 100% at Station Nord in 2011. Our results show that strong winds associated with heavy rain directly affected the reproductive success of some Arctic bird species. Such extreme weather events may become more common with climate change and represent a new potential factor affecting ivory gull breeding success in the High Arctic

Review-Electrode Kinetics and Electrolyte Stability in Vanadium Flow Batteries

Two aspects of vanadium flow batteries are reviewed: electrochemical kinetics on carbon electrodes and positive electrolyte stability. There is poor agreement between reported values of kinetic parameters; however, most authors report that kinetic rates are faster for VIV/VV than for VII/VIII. Cycling the electrode potential increases the rates of both reactions initially due to roughening but when no further roughening is observed, the VII/VIII and VIV/VV reactions are affected oppositely by the pretreatment potential. Anodic pretreatment activates the electrode for the VII/VIII reaction, and deactivates it for VIV/VV. Three states of the carbon surface are suggested: reduced and oxidized states R and O, respectively, both with low electrocatalytic activity, and an intermediate state M with higher activity. The role of surface functional groups and the mechanisms of electron transfer for the VII/VIII and VIV/VV reactions are still not well understood. The induction time for precipitation of V2O5 from positive electrolytes decreases with temperature, showing an Arrhenius-type dependence with an activation energy of 1.79 eV in agreement with DFT calculations based on a VO(OH)3 intermediate. It also decreases exponentially with increasing VV concentration and increases exponentially with increasing sulphate concentration. Both arsenate and phosphate are effective additives for improving thermal stability

Evaluating complementary and alternative medicine interventions: in search of appropriate patient-centered outcome measures

BACKGROUND: Central to the development of a sound evidence base for Complementary and Alternative Medicine (CAM) interventions is the need for valid, reliable and relevant outcome measures to assess whether the interventions work. We assessed the specific needs for a database that would cover a wide range of outcomes measures for CAM research and considered a framework for such a database. METHODS: The study was a survey of CAM researchers, practitioners and students. An online questionnaire was emailed to the members of the Canadian Interdisciplinary Network for CAM Research (IN-CAM) and the CAM Education and Research Network of Alberta (CAMera). The majority of survey questions were open-ended and asked about outcome measures currently used, outcome measures' assessment criteria, sources of information, perceived barriers to finding outcome measures and outcome domains of importance. Descriptive quantitative analysis and qualitative content analysis were used. RESULTS: One hundred and sixty-four completed surveys were received. Of these, 62 respondents reported using outcome measures in their CAM research and identified 92 different specific outcomes. The most important barriers were the fact that, for many health concepts, outcome measures do not yet exist, as well as issues related to accessibility of instruments. Important outcome domains identified included physical, psychological, social, spiritual, quality of life and holistic measures. Participants also mentioned the importance of individualized measures that assess unique patient-centered outcomes for each research participant, and measures to assess the context of healing and the process of healing. CONCLUSION: We have developed a preliminary framework that includes all components of health-related outcomes. The framework provides a foundation for a larger, comprehensive collection of CAM outcomes. It fits very well in a whole systems perspective, which requires an expanded set of outcome measures, such as individualized and holistic measures, with attention to issues of process and context

Staphylococcus aureus α-toxin impairs early neutrophil localization via electrogenic disruption of store-operated calcium entry

The pore-forming S. aureus α-toxin (Hla) contributes to virulence and disease pathogenesis. While high concentrations of toxin induce cell death, neutrophils exhibit relative resistance to lysis, suggesting that the action of Hla may not be solely conferred by lytic susceptibility. Using intravital microscopy, we observed that Hla disrupts neutrophil localization and clustering early in infection. Hla forms a narrow, ion-selective pore, suggesting that Hla may dysregulate calcium or other ions to impair neutrophil function. We found that sub-lytic Hla did not permit calcium influx but caused rapid membrane depolarization. Depolarization decreases the electrogenic driving force for calcium, and concordantly, Hla suppressed calcium signaling in vitro and in vivo and calcium-dependent leukotriene B4 (LTB4) production, a key mediator of neutrophil clustering. Thus, Hla disrupts the early patterning of the neutrophil response to infection, in part through direct impairment of neutrophil calcium signaling. This early mis-localization of neutrophils may contribute to establishment of infection

Automated Large Vessel Occlusion Detection Software and Thrombectomy Treatment Times: a Cluster Randomized Clinical Trial

IMPORTANCE: The benefit of endovascular stroke therapy (EVT) in large vessel occlusion (LVO) ischemic stroke is highly time dependent. Process improvements to accelerate in-hospital workflows are critical. OBJECTIVE: to determine whether automated computed tomography (CT) angiogram interpretation coupled with secure group messaging can improve in-hospital EVT workflows. DESIGN, SETTING, AND PARTICIPANTS: This cluster randomized stepped-wedge clinical trial took place from January 1, 2021, through February 27, 2022, at 4 comprehensive stroke centers (CSCs) in the greater Houston, Texas, area. All 443 participants with LVO stroke who presented through the emergency department were treated with EVT at the 4 CSCs. Exclusion criteria included patients presenting as transfers from an outside hospital (n = 158), in-hospital stroke (n = 39), and patients treated with EVT through randomization in a large core clinical trial (n = 3). INTERVENTION: Artificial intelligence (AI)-enabled automated LVO detection from CT angiogram coupled with secure messaging was activated at the 4 CSCs in a random-stepped fashion. Once activated, clinicians and radiologists received real-time alerts to their mobile phones notifying them of possible LVO within minutes of CT imaging completion. MAIN OUTCOMES AND MEASURES: Primary outcome was the effect of AI-enabled LVO detection on door-to-groin (DTG) time and was measured using a mixed-effects linear regression model, which included a random effect for cluster (CSC) and a fixed effect for exposure status (pre-AI vs post-AI). Secondary outcomes included time from hospital arrival to intravenous tissue plasminogen activator (IV tPA) bolus in eligible patients, time from initiation of CT scan to start of EVT, and hospital length of stay. In exploratory analysis, the study team evaluated the impact of AI implementation on 90-day modified Rankin Scale disability outcomes. RESULTS: Among 243 patients who met inclusion criteria, 140 were treated during the unexposed period and 103 during the exposed period. Median age for the complete cohort was 70 (IQR, 58-79) years and 122 were female (50%). Median National Institutes of Health Stroke Scale score at presentation was 17 (IQR, 11-22) and the median DTG preexposure was 100 (IQR, 81-116) minutes. In mixed-effects linear regression, implementation of the AI algorithm was associated with a reduction in DTG time by 11.2 minutes (95% CI, -18.22 to -4.2). Time from CT scan initiation to EVT start fell by 9.8 minutes (95% CI, -16.9 to -2.6). There were no differences in IV tPA treatment times nor hospital length of stay. In multivariable logistic regression adjusted for age, National Institutes of Health Stroke scale score, and the Alberta Stroke Program Early CT Score, there was no difference in likelihood of functional independence (modified Rankin Scale score, 0-2; odds ratio, 1.3; 95% CI, 0.42-4.0). CONCLUSIONS AND RELEVANCE: Automated LVO detection coupled with secure mobile phone application-based communication improved in-hospital acute ischemic stroke workflows. Software implementation was associated with clinically meaningful reductions in EVT treatment times. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05838456

Identification of Radiopure Titanium for the LZ Dark Matter Experiment and Future Rare Event Searches

The LUX-ZEPLIN (LZ) experiment will search for dark matter particle interactions with a detector containing a total of 10 tonnes of liquid xenon within a double-vessel cryostat. The large mass and proximity of the cryostat to the active detector volume demand the use of material with extremely low intrinsic radioactivity. We report on the radioassay campaign conducted to identify suitable metals, the determination of factors limiting radiopure production, and the selection of titanium for construction of the LZ cryostat and other detector components. This titanium has been measured with activities of $^{238}$U$_{e}$~$<$1.6~mBq/kg, $^{238}$U$_{l}$~$<$0.09~mBq/kg, $^{232}$Th$_{e}$~$=0.28\pm 0.03$~mBq/kg, $^{232}$Th$_{l}$~$=0.25\pm 0.02$~mBq/kg, $^{40}$K~$<$0.54~mBq/kg, and $^{60}$Co~$<$0.02~mBq/kg (68\% CL). Such low intrinsic activities, which are some of the lowest ever reported for titanium, enable its use for future dark matter and other rare event searches. Monte Carlo simulations have been performed to assess the expected background contribution from the LZ cryostat with this radioactivity. In 1,000 days of WIMP search exposure of a 5.6-tonne fiducial mass, the cryostat will contribute only a mean background of $0.160\pm0.001$(stat)$\pm0.030$(sys) counts.Comment: 13 pages, 3 figures, accepted for publication in Astroparticle Physic