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Abstract Thyrotoxic periodic paralysis (TPP) is rarely seen in children and adolescents. Clinical manifestations in children and adolescents may vary. It is important for clinicians to be aware of this rare and life‐threatening condition.

Created by street artist Shepard Fairey, the protest poster, “We the People are Greater than Fear,” emerged as a powerful visual response to the 2016 election of Donald Trump. Though celebrated as a progressive symbol of inclusion, we argue the poster, perhaps unwittingly, reinforces some of the very prejudices it seeks to confront by associating Muslimness with suspicion, foreignness, and fear. Using “Greater than Fear” as a case study, this essay contributes to scholarship combining critical affect theory with rhetorical studies by theorizing affective blockage as a means of understanding the ways affect contributes to the resilience of hegemonic narratives by preventing certain meanings from surfacing. We argue the poster reveals a cautionary lesson about how affect can obscure critique of cultural texts created with progressive intent, inadvertently bolstering softer, more subtle forms of racism embedded in liberal contexts. We also discuss the importance of interrogating rehearsed affective associations that, by virtue of their familiarity, seem normal and acceptable but ultimately reinforce exploitative conceptions related to identity categories such as race, religion, sexuality, class, and gender. We conclude with insights for rhetorical scholars about how affective associations can enable ostensibly liberal discourses while at the same time preventing their critique. [ABSTRACT FROM AUTHOR]

Abstract Ocean ecosystems have been subjected to anthropogenic influences for centuries, but the scale of past ecosystem changes is often unknown. For centuries, the European flat oyster (Ostrea edulis), an ecosystem engineer providing biogenic reef habitats, was a culturally and economically significant source of food and trade. These reef habitats are now functionally extinct, and almost no memory of where or at what scales this ecosystem once existed, or its past form, remains. The described datasets present qualitative and quantitative extracts from written records published between 1524 and 2022. These show: (1) locations of past flat oyster fisheries and/or oyster reef habitat described across its biogeographical range, with associated levels of confidence; (2) reported extent of past oyster reef habitats, and; (3) species associated with these habitats. These datasets will be of use to inform accelerating flat oyster restoration activities, to establish reference models for anchoring adaptive management of restoration action, and in contributing to global efforts to recover records on the hidden history of anthropogenic-driven ocean ecosystem degradation.

Abstract The Mantel Test, discovered in the 1960s, determines whether two distance metrics on a network are related. More recently, DimeCost, an equivalent test with improved computational complexity, was proposed. It was based on computing a random spanning tree of a complete graph on n vertices—the spanning tree was computed using Wilson’s random walk algorithm. In this paper, we describe DC-RST, a parallel, divide-and-conquer random walk algorithm to further speed up this computation. Relative to Wilson’s sequential random-walk algorithm, on a system with 48 cores, DC-RST was up to 4X faster when first creating random partitions and up to 20X faster without this sub-step. DC-RST is shown to be a suitable replacement for the Mantel and DimeCost tests through a combination of theoretical and statistical results.

Titanium carbide (Ti3C2Tx) MXene has attracted significant attention due to its exceptional properties and versatile solution processibility. However, MXene dispersions are prone to various degradation processes, leading to the formation of byproducts that negatively affect its morphological, electrical, and mechanical properties. Through the years, several methods have been developed to mitigate MXene degradation; however, divergent viewpoints on the understanding of degradation mechanisms are prevalent, hindering the development of versatile strategies in producing environmentally stable MXene dispersions. This review provides a chronological analysis of the research efforts aimed at unraveling the underlying mechanisms of MXene degradation and highlights strategies for circumventing this process. This review discusses apparent inconsistencies in experimental findings and theoretical models. These discrepancies prompt further investigation for a clearer understanding of the degradation process in MXene. This narrative allows readers to follow the evolution of dominant theories and disputes and to ultimately stimulate further investigation, aiming for a better understanding of this process. It is anticipated that identifying the fundamental factors affecting the oxidation of MXene dispersions will enable their full‐scale processing into higher‐order structures and practical devices with greater longevity and long‐term performance.

Coolant-facing alloys in a tokamak will face harsh environments due to the synergistic effect of flowing coolant, dynamic mechanical loading, ionising radiation, and tritium embrittlement. Reduced activation ferritic/martensitic (RAF/M) EUROFER-97 is the primary candidate as the structural alloy for the breeder blanket to be used in DEMO reactor. Under fusion-like conditions, coatings are required to improve both its corrosion properties and act as a tritium permeation barrier (TPB) layer. In this study, Al-base self-passivating coatings have been investigated as possible solution to provide protection against corrosion and act as TPB layer. The aim of this study was to assess the adhesion properties between different self-passivating Al-base coatings as electroplated and chemical vapour deposited (CVD) coatings on a RAF/M EUROFER-97 under strain. These studies showed the high ductility of pure electroplated Al-coatings, whereas both CVD coatings cracked under the applied strain.

Neonates are more susceptible to influenza virus infection than adults, resulting in increased morbidity and mortality and delayed clearance of the virus. Generating effective CD8+ T cell responses may be important for improving vaccination outcomes in vulnerable populations, but neonatal T cells frequently respond differently than adult cells. We sought to understand CD8+ T cell specificity and immunodominance during neonatal influenza infection and how any differences from the adult hierarchy might impact peptide vaccine effectiveness. Neonatal C57BL/6 mice displayed an altered CD8+ T cell immunodominance hierarchy during influenza infection, preferentially responding to an epitope in the influenza protein PA rather than the co-dominant adult response to NP and PA. Heterosubtypic infections in mice first infected as pups also displayed altered immunodominance and reduced protection compared to mice first infected as adults. Adoptive transfer of influenza-infected bone-marrow-derived dendritic cells promoted an NP-specific CD8+ T cell response in influenza-virus-infected pups and increased viral clearance. Finally, pups responded to PA (224–233), but not NP (366–374) during peptide vaccination. PA (224–233)-vaccinated mice were not protected during viral challenge. Epitope usage should be considered when designing vaccines that target T cells when the intended patient population includes infants and adults.

Today’s social and political movements against dominant Western narratives call for a re-contextualization of cultural heritage (CH) toward inclusivity, multiperspectivity, and sensemaking. Our work approaches this challenge from a Human–Computer Interaction (HCI) perspective, questioning how HCI approaches, tools and methods can contribute to CH re-contextualization. Through collaborative reflection on our research practice, we identified four diverging case studies highlighting the different roles of HCI and its increasing entanglement with CH. Case studies 1–3 focus on HCI as a medium for CH, case 4 on digital CH, and thereby on the HCI–CH entanglement. Our reflections contribute to CH re-contextualization by highlighting the need for co-design and slow design approaches, the role of HCI technologies in preserving, communicating, and shaping CH, and open questions and challenges related to the increasing HCI–CH convergence.

Background: Prior studies have shown variation in the intensity of end-of-life care in intensive care units (ICUs) among patients of different races. Objective: We sought to identify variation in the levels of care at the end of life in the ICU and to assess for any association with race and ethnicity. Design: An observational, retrospective cohort study. Settings: A tertiary care center in Boston, MA. Participants: All critically ill patients admitted to medical and surgical ICUs between June 2019 and December 2020. Exposure: Self-identified race and ethnicity. Main Outcome and Measure: The primary outcome was death. Secondary outcomes included ?code status,? markers of intensity of care, consultation by the Palliative care service, and consultation by the Ethics service. Results: A total of 9083 ICU patient encounters were analyzed. One thousand two hundred fifty-nine patients (14%) died in the ICU; the mean age of patients was 64 years (standard deviation 16.8), and 44% of patients were women. A large number of decedents (22.7%) did not have their race identified. These patients had a high rate of interventions at death. Code status varied by race, with more White patients designated as ?Comfort Measures Only? (CMO) (74%) whereas more Black patients were designated as ?Do Not Resuscitate/Do Not Intubate (DNR/DNI) and DNR/ok to intubate? (12.1% and 15.7%) at the end of life; after adjustment for age and severity of illness, there were no statistical differences by race for the use of the CMO code status. Use of dialysis at the end of life varied by self-identified race. Specifically, Black and Unknown patients were more likely to receive renal replacement therapy, even after adjustment for age and severity of illness (24% and 20%, p?=?0.003). Conclusions: Our data describe a gap in identification of race and ethnicity, as well as differences at the end of life in the ICU, especially with respect to code status and certain markers of intensity.

Abstract Microglial activation plays central roles in neuroinflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18 kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases in activated microglia in mouse brain disease models but does not change in a non-human primate disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter, consistent with the hypothesis that the increase in TSPO expression in activated myeloid cells depends on the transcription factor AP1 and is unique to a subset of rodent species within the Muroidea superfamily. Finally, we identify LCP2 and TFEC as potential markers of microglial activation in humans. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO-PET signals in humans reflect the density of inflammatory cells rather than activation state.

This retrospective study aimed to evaluate the performance of hormone treatment protocols, determine the factors associated with pregnancy success after hormone treatment, and compare the cost-efficiencies of two types of hormone treatment among cyclic and noncyclic anestrous dairy cows. The clinical records of 279 anestrous cows that received hormone treatment for artificial insemination (AI) from 64 herds in the western region of Thailand were obtained from Kasetsart University Veterinary Teaching Hospital from January to August 2017. The performance of the hormone treatment protocols, fixed-time AI (TAI) and estrus detection before AI (EAI), showed that the pregnancy risk for the TAI protocol was higher than that for the EAI protocol, but pregnancy per AI did not differ significantly between the two protocols in cyclic and noncyclic cows. Multivariate logistic regression analysis showed that cows receiving the TAI protocol were more likely to be pregnant compared to those treated with the EAI protocol. Cows with a 3.00 body condition score (BCS) < 3.75 after treatment and loose-housed cows were more likely to become pregnant. Treatment during winter showed higher pregnancy success than that in the summer and rainy seasons. The cost-efficiency analysis showed that the TAI protocol was the most cost-efficient option for noncyclic cows, whereas the EAI protocol was the most cost-efficient option for cyclic cows.

Pulmonary function tests (PFTs) are usually interpreted by clinicians using rule-based strategies and pattern recognition. The interpretation, however, has variabilities due to patient and interpreter errors. Most PFTs have recognizable patterns that can be categorized into specific physiological defects. In this study, we developed a computerized algorithm using the python package (pdfplumber) and validated against clinicians' interpretation. We downloaded PFT reports in the electronic medical record system that were in PDF format. We digitized the flow volume loop (FVL) and extracted numeric values from the reports. The algorithm used FEV1/FVC120%pred for abnormal DLCO. The algorithm also used a small airway disease index (SADI) to quantify late expiratory flattening of the FVL to assess small airway dysfunction. We devised keywords for the python Natural Language Processing (NLP) package (spaCy) to identify obstruction, restriction, abnormal DLCO and small airway dysfunction in the reports. The algorithm was compared to clinicians' interpretation in 6,889 PFTs done between March 1st, 2018, and September 30th, 2020. The agreement rates (Cohen's kappa) for obstruction, restriction and abnormal DLCO were 94.4% (0.868), 99.0% (0.979) and 87.9% (0.750) respectively. In 4,711 PFTs with FEV1/FVC≥0.7, the algorithm identified 190 tests with SADI < lower limit of normal (LLN), suggesting small airway dysfunction. Of these, the clinicians (67.9%) also flagged 129 tests. When SADI was ≥ LLN, no clinician's reports indicated small airway dysfunction. Our results showed the computerized algorithm agreed with clinicians' interpretation in approximately 90% of the tests and provided a sensitive objective measure for assessing small airway dysfunction. The algorithm can improve efficiency and consistency and decrease human errors in PFT interpretation. The computerized algorithm works directly on PFT reports in PDF format and can be adapted to incorporate a different interpretation strategy and platform.

Rickettsiae include diverse Gram-negative microbial species that exhibit obligatory intracellular lifecycles between mammalian hosts and arthropod vectors. Human infections with arthropod-borne Rickettsia continue to cause significant morbidity and mortality as recent environmental changes foster the proliferation of arthropod vectors and increased exposure to humans. However, the technical difficulties in working with Rickettsia have delayed our progress in understanding the molecular mechanisms involved in rickettsial pathogenesis and disease transmission. Recent advances in developing genetic tools for Rickettsia have enabled investigators to identify virulence genes, uncover molecular functions, and characterize host responses to rickettsial determinants. Therefore, continued efforts to determine virulence genes and their biological functions will help us understand the underlying mechanisms associated with arthropod-borne rickettsioses.

A mechanically strong binder with polar functional groups could overcome the dilemma of the large volume change during charge/discharge processes and poor cyclability of lithium-sulfur batteries (LSBs). In this work, for the first time, we report the use of poly(thiourea triethylene glycol) (PTTG) as a multifunctional binder for sulfur cathodes to enhance the performance of LSBs. As expected, the PTTG binder facilitates the high performance and stability delivered by the Sulfur-PTTG cathode, including a higher reversible capacity of 825 mAh g−1 at 0.2 C after 80 cycles, a lower capacity fading (0.123% per cycle) over 350 cycles at 0.5 C, a higher areal capacity of 2.5 mAh cm−2 at 0.25 mA cm−2, and better rate capability of 587 mAh g−1 at 2 C. Such superior electrochemical performances could be attributed to PTTG's strong chemical adsorption towards polysulfides which may avoid the lithium polysulfide shuttle effect and excellent mechanical characteristics which prevents electrode collapse during cycling and allows the Sulfur-PTTG electrode to maintain robust electron and ion migration pathways for accelerated redox reaction kinetics.

Summary: Background: B cells can be enriched within meningeal immune-cell aggregates of multiple sclerosis (MS) patients, adjacent to subpial cortical demyelinating lesions now recognized as important contributors to progressive disease. This subpial demyelination is notable for a ‘surface-in’ gradient of neuronal loss and microglial activation, potentially reflecting the effects of soluble factors secreted into the CSF. We previously demonstrated that MS B-cell secreted products are toxic to oligodendrocytes and neurons. The potential for B-cell–myeloid cell interactions to propagate progressive MS is of considerable interest. Methods: Secreted products of MS-implicated pro-inflammatory effector B cells or IL-10-expressing B cells with regulatory potential were applied to human brain-derived microglia or monocyte-derived macrophages, with subsequent assessment of myeloid phenotype and function through measurement of their expression of pro-inflammatory, anti-inflammatory and homeostatic/quiescent molecules, and phagocytosis (using flow cytometry, ELISA and fluorescently-labeled myelin). Effects of secreted products of differentially activated microglia on B-cell survival and activation were further studied. Findings: Secreted products of MS-implicated pro-inflammatory B cells (but not IL-10 expressing B cells) substantially induce pro-inflammatory cytokine (IL-12, IL-6, TNFα) expression by both human microglia and macrophage (in a GM-CSF dependent manner), while down-regulating their expression of IL-10 and of quiescence-associated molecules, and suppressing their myelin phagocytosis. In contrast, secreted products of IL-10 expressing B cells upregulate both human microglia and macrophage expression of quiescence-associated molecules and enhance their myelin phagocytosis. Secreted factors from pro-inflammatory microglia enhance B-cell activation. Interpretation: Potential cross-talk between disease-relevant human B-cell subsets and both resident CNS microglia and infiltrating macrophages may propagate CNS-compartmentalized inflammation and injury associated with MS disease progression. These interaction represents an attractive therapeutic target for agents such as Bruton's tyrosine kinase inhibitors (BTKi) that modulate responses of both B cells and myeloid cells. Funding: Stated in Acknowledgments section of manuscript.

The growing pervasiveness of digital technologies has exposed the entanglements of Human-Computer Interaction (HCI) with its surrounding context, from the immediate vicinity of interfaces to global issues. While often providing solutions to societal issues, interactive technologies also many times contribute to them. They impact and are impacted by the world, in a process of continuous mutual influence and co-constitution that raises important implications not only to user experience, effectiveness and efficiency, but also to ethics, social responsibility and environmental health. In this article, I draw on the new materialism notion of intra-action to propose a conceptual shift to a relational approach for HCI, which I refer to as Human-Computer Intra-Action (HCIA), capable of capturing from the outset the inherent relationships with the world that inform the design of interactive technology. To that end, I propose the notion of relationalities to reflect the synergies and antagonisms around those relationships, and discuss emerging notions of spatiality and temporality by considering the increasing hybridity of socio-technical engagements both in space (local vs. remote) and in time (immediate vs. stretched). Based on that, I propose a preliminary method for mapping intra-actions associated to interactive technologies, envisaged as a starting point to a relational take on their design process.

Epiabm is an open-source software package for epidemiological agent-based modelling, re-implementing the well-known CovidSim model from the MRC Centre for Global Infectious Disease Analysis at Imperial College London. It has been developed as part of the first-year training programme in the EPSRC SABS:R3 Centre for Doctoral Training at the University of Oxford. The model builds an age-stratified, spatially heterogeneous population and offers a modular approach to configure and run epidemic scenarios, allowing for a broad scope of investigative and comparative studies. Two simulation backends are provided: a pedagogical Python backend (with full functionality) and a high performance C++ backend for use with larger population simulations. Both are highly modular, and include a comprehensive testing suite (including 100% coverage on unit tests alongside a range of functional and integration tests), as well as complete online documentation for ease of understanding and extensibility. Epiabm is publicly available through GitHub at github.com/SABS-R3-Epidemiology/epiabm.

How can scholars approach The Secret World Legends (2017), an obscure game rooted in colonialism, as a source of critique that inspires decolonial futures in media broadly? By applying critical frameworks towards the horror genre and RPG format the game inhabits, this essay continues the work of naming and challenging oppressive systems and narratives embedded in video games and their network. At the same time this essay works to produce subversive readings where both player subjectivity and the game challenges colonialism and imagine decolonial futures through its play. This essay conclude that the combined efforts of play and critique, playing against colonial games, and playing games that deliberately center marginalized experiences, voices and communities, work towards just futures in media that players and researchers must be attentive of.

The vestibular maculae of the inner ear contain sensory receptor hair cells that detect linear acceleration and contribute to equilibrioception to coordinate posture and ambulatory movements. These hair cells are divided between two groups, separated by a line of polarity reversal (LPR), with oppositely oriented planar-polarized stereociliary bundles that detect motion in opposite directions. The transcription factor EMX2 is known to establish this planar polarized organization in mouse by regulating the distribution of the transmembrane receptor GPR156 at hair cell boundaries in one group of cells. However, the genes regulated by EMX2 in this context were previously not known. Using mouse as a model, we have identified the serine threonine kinase STK32A as a downstream effector negatively regulated by EMX2. Stk32a is expressed in hair cells on one side of the LPR in a pattern complementary to Emx2 expression in hair cells on the opposite side. Stk32a is necessary to align the intrinsic polarity of the bundle with the core planar cell polarity (PCP) proteins in EMX2-negative regions, and is sufficient to reorient bundles when ectopically expressed in neighboring EMX2-positive regions. We demonstrate that STK32A reinforces LPR formation by regulating the apical localization of GPR156. These observations support a model in which bundle orientation is determined through separate mechanisms in hair cells on opposite sides of the maculae, with EMX2-mediated repression of Stk32a determining the final position of the LPR.

Background and Aim: Bovine viral diarrhea virus (BVDV) and classical swine fever virus (CSFV) are important pathogens of cattle and pigs, respectively, and belong to the genus Pestivirus. As CSFV has been shown to infect cattle, it can create diagnostic challenges of BVDV results through possible cross-reactivity where cattle could be exposed to pigs and CSFV. This study aimed to determine the possible cross-reactivity of BVDV and CSFV enzyme-linked immunosorbent assay (ELISA) results for antigen (Ag) and antibody (Ab) among smallholder dairy cattle in Kenya. Materials and Methods: This was a cross-sectional study based on a single visit to farms to collect serum samples and other descriptive farm-level and animal-level information. Testing for BVDV Ag and Ab was conducted on serum samples from 320 dairy cows and heifers, with CSFV Ag and Ab testing conducted on a subset of 133 and 74 serum samples, respectively. CSFV testing was based on BVDV test results and the availability of enough sample volume from farms that kept pigs. The Ag and Ab tests utilized IDEXX ELISA for both BVDV and CSFV. Results: For the 74 samples with Ab tests for both viruses, 40 (54.0%) were BVDV Ab positive, while 63 (85.1%) were CSFV Ab positive. Of the 40 BVDV Ab positive samples, 36 cattle (90.0%) tested positive for CSFV Ab. However, of the 34 BVDV Ab negative samples, 27 (79.4%) were CSFV Ab test-positive. For the 133 samples with Ag tests for both viruses, 125 (94.0%) were BVDV Ag positive, while 2 (1.5%) samples were CSFV Ag positive. None of the eight BVDV Ag negative samples was positive for CSFV Ag and only two (1.6%) of the 125 BVDV Ag positive samples were positive for CSFV Ag. Conclusion: The results indicate either substantial cross-reactivity of the two Ab ELISA tests, or reactivity with some other protein in the samples that led to the positive Ab test results. There was only limited evidence for cross-reactivity of the two Ag ELISA tests. We recommend that Pestivirus genus cross-reactivity be considered when interpreting BVDV ELISA results in cattle, more for Ab than Ag tests. Further research is needed to clarify the levels of cross-reactivity between BVDV and other Pestivirus Ag and Ab tests from animals on mixed-species farms.

This paper explores how authentic assessment can be implemented to enhance opportunities to develop employability skills through problem-solving tasks. Based on the eight key tenets of authentic assessment (Ashford-Rowe, Herrington and Brown, 2014), this paper presents formative and summative assessment case studies which were created in partnership with external stakeholders on three separate degree programmes at an undergraduate college-based higher education provider. The case studies report on the development of employability skills through authentic learning design on courses ranging from level 4 to level 6 of the Framework for Higher Education Qualifications. The cases add weight to the argument for embedding employability within the curriculum wherein the core skills/intended outcomes are delivered as part of the taught curriculum rather than as paralleled approaches which aim to develop employability as an add-on. Each of the case studies are individually distinct, however they each share commonalities that collectively produce an effective framework for authentic assessment design. These key components include effective collaboration with external stakeholders (employers) from within the respective sectors, the joint formulation of a ‘problem’ that allows students to apply real world skillsets to overcome, and lastly the opportunity for external stakeholders to contribute towards feedback that students receive in respect to the assessment carried out. Learning developers in higher education should look to utilise the conclusions of this paper to inform learning design in their contexts.

Tailoring the macroscopic properties of deep eutectic solvents requires knowing how these depend on the local structure and microscopic dynamics. The authors, with computational and experimental tools spanning a wide range of space- and timescales, shed light into the relationship between micro and macroscopic properties in glyceline and ethaline.

Abstract Background An imbalance between inhibitory and excitatory neurometabolites has been implicated in chronic pain. Prior work identified elevated levels of Gamma-aminobutyric acid + macromolecules (“GABA+”) using magnetic resonance spectroscopy (MRS) in people with migraine. What is not understood is whether this increase in GABA+ is a cause, or consequence of living with, chronic migraine. Therefore, to further elucidate the nature of the elevated GABA+ levels reported in migraine, this study aimed to observe how GABA+ levels change in response to changes in the clinical characteristics of migraine over time. Methods We observed people with chronic migraine (ICHD-3) over 3-months as their treatment was escalated in line with the Australian Pharmaceutical Benefits Scheme (PBS). Participants underwent an MRS scan and completed questionnaires regarding migraine frequency, intensity (HIT-6) and disability (WHODAS) at baseline and following the routine 3 months treatment escalation to provide the potential for some participants to recover. We were therefore able to monitor changes in brain neurochemistry as clinical characteristics potentially changed over time. Results The results, from 18 participants who completed both baseline and follow-up measures, demonstrated that improvements in migraine frequency, intensity and disability were associated with an increase in GABA+ levels in the anterior cingulate cortex (ACC); migraine frequency (r = − 0.51, p = 0.03), intensity (r = − 0.51, p = 0.03) and disability (r = − 0.53, p = 0.02). However, this was not seen in the posterior cingulate gyrus (PCG). An incidental observation found those who happened to have their treatment escalated with CGRP-monoclonal antibodies (CGRP-mAbs) (n = 10) had a greater increase in ACC GABA+ levels (mean difference 0.54 IU IQR [0.02 to 1.05], p = 0.05) and reduction in migraine frequency (mean difference 10.3 IQR [2.52 to 18.07], p = 0.01) compared to those who did not (n = 8). Conclusion The correlation between an increase in ACC GABA+ levels with improvement in clinical characteristics of migraine, suggest previously reported elevated GABA+ levels may not be a cause of migraine, but a protective mechanism attempting to suppress further migraine attacks.

This paper assesses the contribution of innovation persistence to surviving Australian firm growth performance over the period 2007–08 to 2013–14 with the added advantages that new firms, micro-sized firms and all industry sectors are included in our analysis. Over this period, firms with high sales and/or employment growth accounted for the majority of aggregate economic and employment growth in Australia, which is consistent with similar studies in other countries. Using a randomized, stratified sample from a firm population-level database that links administrative, tax and survey data, we created a matched, balanced sample of surviving firms to show that short-term persistent innovators (particularly young SMEs) significantly outgrow their less persistent and non-innovator counterparts in terms of sales, value added, employment and profit growth. Persistent innovators are more likely to be high-growth firms and more likely to introduce multiple types of innovation that are more novel. Our findings suggest that broad-based innovation policies may support successive waves of high-growth firms that help to sustain economic and employment growth in Australia.

The augmentation of the built and urban environment with digital media has evolved and matured over recent years. Cities are seeing a rapid rise of various technologies; a trend also accelerated by global crises. Consequently, new urban interfaces are emerging that integrate next-generation technologies, such as sustainable interface materials and urban robotic systems. However, their development is primarily driven by technological concerns, leaving behind social, aesthetic, and spatial considerations. By analyzing our own media architecture research projects and real-world applications from the past two decades, we offer a structural approach for developing these new urban interfaces. The individual cases provide early insights and challenges related to prototyping and augmenting contexts with novel input and output modalities. These results in common, preliminary observed patterns in the process of integrating next-generation technologies into urban environments and surroundings, in response to continuously evolving social needs.

In recent years, the U.S. Food and Drug Administration (FDA) has seen an increase in microfluidic medical device submissions, likely stemming from recent advancements in microfluidic technologies. This recent trend has only been enhanced during the COVID-19 pandemic, as microfluidic-based test kits have been used for diagnosis. To better understand the implications of this emerging technology, device submissions to the FDA from 2015 to 2021 containing microfluidic technologies have been systematically reviewed to identify trends in microfluidic medical applications, performance tests, standards used, fabrication techniques, materials, and flow systems. More than 80% of devices with microfluidic platforms were found to be diagnostic in nature, with lateral flow systems accounting for about 35% of all identified microfluidic devices. A targeted analysis of over 40,000 adverse event reports linked to microfluidic technologies revealed that flow, operation, and data output related failures are the most common failure modes for these device types. Lastly, this paper highlights key considerations for developing new protocols for various microfluidic applications that use certain analytes (e.g., blood, urine, nasal-pharyngeal swab), materials, flow, and detection mechanisms. We anticipate that these considerations would help facilitate innovation in microfluidic-based medical devices.

Abstract The human cochlea transforms sound waves into electrical signals in the acoustic nerve fibers with high acuity. This transformation occurs via vibrating anisotropic membranes (basilar and tectorial membranes) and frequency-specific hair cell receptors. Frequency-positions can be mapped within the cochlea to create a tonotopic chart which fits an almost-exponential function with lowest frequencies positioned apically and highest frequencies positioned at the cochlear base (Bekesy 1960, Greenwood 1961). To date, models of frequency positions have been based on a two-dimensional analysis with inaccurate representations of the cochlear hook region. In the present study, the first three-dimensional frequency analysis of the cochlea using dendritic mapping to obtain accurate tonotopic maps of the human basilar membrane/organ of Corti and the spiral ganglion was performed. A novel imaging technique, synchrotron radiation phase-contrast imaging, was used and a spiral ganglion frequency function was estimated by nonlinear least squares fitting a Greenwood-like function (F = A (10 ax − K)) to the data. The three-dimensional tonotopic data presented herein has large implications for validating electrode position and creating customized frequency maps for cochlear implant recipients.

Abstract Intravascular missile emboli to the right heart should be retrieved surgically if the risk of surgical complication due to sternotomy and cardiotomy is low. Endovascular retrieval is another possible method of extraction to be considered.

The European flat oyster (Ostrea edulis) is a bivalve mollusc that was once widely distributed across Europe and represented an important food resource for humans for centuries. Populations of O. edulis experienced a severe decline across their biogeographic range mainly due to overexploitation and disease outbreaks. To restore the economic and ecological benefits of European flat oyster populations, extensive protection and restoration efforts are in place within Europe. In line with the increasing interest in supporting restoration and oyster farming through the breeding of stocks with enhanced performance, the present study aimed to evaluate the potential of genomic selection for improving growth traits in a European flat oyster population obtained from successive mass-spawning events. Four growth-related traits were evaluated: total weight (TW), shell height (SH), shell width (SW) and shell length (SL). The heritability of the growth traits was in the low-moderate range, with estimates of 0.45, 0.37, 0.22, and 0.32 for TW, SH, SW and SL, respectively. A genome-wide association analysis revealed a largely polygenic architecture for the four growth traits, with two distinct QTLs detected on chromosome 4. To investigate whether genomic selection can be implemented in flat oyster breeding at a reduced cost, the utility of low-density SNP panels was assessed. Genomic prediction accuracies using the full density panel were high (> 0.83 for all traits). The evaluation of the effect of reducing the number of markers used to predict genomic breeding values revealed that similar selection accuracies could be achieved for all traits with 2K SNPs as for a full panel containing 4,577 SNPs. Only slight reductions in accuracies were observed at the lowest SNP density tested (i.e., 100 SNPs), likely due to a high relatedness between individuals being included in the training and validation sets during cross-validation. Overall, our results suggest that the genetic improvement of growth traits in oysters is feasible. Nevertheless, and although low-density SNP panels appear as a promising strategy for applying GS at a reduced cost, additional populations with different degrees of genetic relatedness should be assessed to derive estimates of prediction accuracies to be expected in practical breeding programmes.

Background: Loss of reduction (LoR) can occur after locking plate fixation of proximal humerus fractures (PHFs). This study determined biomechanical features of fracture fixation associated with preventing LoR postoperatively. One-year reoperation rates were also compared between those with/without LoR. Methods: Population-based administrative data for 359 adults treated using a locking plate for PHF between 2010 and 2016 were examined. Two trained assessors reviewed standardized shoulder radiographs. LoR (Yes/No) was defined as any fracture displacement >0.5 cm, and/or >10° change in neck-shaft angle (NSA) alignment relative to intraoperative imaging. Multiple logistic regression assessed how the following affected maintaining reduction: (1) sex, (2) age, (3) Neer classification, (4) shaft impaction (SI), (5) shaft medialization (SM), (6) calcar reduction (CR), (7) NSA alignment, and (8) screw use. Results: LoR was seen in 79 (22%) patients. LoR was significantly associated with increasing age (odds ratio [OR] = 1.06/yr, P < .001), fracture severity (4-part vs. 2-part fracture; OR = 4.63, P = .001), and varus NSA alignment (

Abstract Background Many lines of evidence suggest that accumulation of aggregated alpha-synuclein (αSYN) in the Parkinson’s disease (PD) brain causes infiltration of T cells. However, in which ways the stationary brain cells interact with the T cells remain elusive. Here, we identify astrocytes as potential antigen-presenting cells capable of activating T cells in the PD brain. Astrocytes are a major component of the nervous system, and accumulating data indicate that astrocytes can play a central role during PD progression. Methods To investigate the role of astrocytes in antigen presentation and T-cell activation in the PD brain, we analyzed post mortem brain tissue from PD patients and controls. Moreover, we studied the capacity of cultured human astrocytes and adult human microglia to act as professional antigen-presenting cells following exposure to preformed αSYN fibrils. Results Our analysis of post mortem brain tissue demonstrated that PD patients express high levels of MHC-II, which correlated with the load of pathological, phosphorylated αSYN. Interestingly, a very high proportion of the MHC-II co-localized with astrocytic markers. Importantly, we found both perivascular and infiltrated CD4+ T cells to be surrounded by MHC-II expressing astrocytes, confirming an astrocyte T cell cross-talk in the PD brain. Moreover, we showed that αSYN accumulation in cultured human astrocytes triggered surface expression of co-stimulatory molecules critical for T-cell activation, while cultured human microglia displayed very poor antigen presentation capacity. Notably, intercellular transfer of αSYN/MHC-II deposits occurred between astrocytes via tunneling nanotubes, indicating spreading of inflammation in addition to toxic protein aggregates. Conclusions In conclusion, our data from histology and cell culture studies suggest an important role for astrocytes in antigen presentation and T-cell activation in the PD brain, highlighting astrocytes as a promising therapeutic target in the context of chronic inflammation.

Background: Ankle fractures are common and frequently managed with open reduction and internal fixation (ORIF). Although these fractures can occur at any age, they are most common in younger individuals with high-energy trauma or older adults with lower-energy trauma. Our investigation focused on those aged 65 years or younger. Our primary objective was to describe recovery over the first postfracture year in (1) functional dorsiflexion using the weightbearing lunge test (WBLT), (2) patient-reported functional outcomes using the Olerud Molander Ankle Score (OMAS), (3) return to prefracture activity levels, and (4) return to work. Secondarily, we examined patient and clinical factors (including the WBLT and OMAS) associated with return to prefracture activities, including sports. Methods: Using a prospective inception cohort of 142 patients between 18 and 65 years old who underwent ORIF after ankle fracture and attended follow-up visits, we collected information from participants and their medical charts. We assessed functional dorsiflexion (using side-to-side difference in WBLT), patient-reported functional outcome (OMAS), and self-reported return to prefracture activity levels and work at 6 weeks, 6 months and 1 year postoperatively. Results: The WBLT, OMAS, and return to prefracture activity and work improved significantly over time ( P < .001). However, at 1 year postoperation, the mean side-to-side difference in the WBLT was 3.22±2.68 cm, 69 (72%) reported ankle stiffness, and only 49 (52%) had returned to prefracture activity levels. Of those who were working, 97% had returned to work by 1 year postoperation. Only the OMAS ( P < .001) and side-to-side difference in WBLT ( P = .011) were significantly associated with return to prefracture activity levels. Conclusion: Although participants improved significantly over the first postoperative year in all outcomes, many reported limitations in functional dorsiflexion and return to prefracture activities. Those with higher OMAS scores and smaller side-to-side difference in WBLT were more likely to return to prefracture activity levels by 1 year postoperatively. Level of Evidence: Level II, prognostic study.

Abstract The sulfur cathode of lithium‐sulfur (Li‐S) batteries suffers from inherent problems of insufficient mechanical strength and the dissolution of sulfur and polysulfides. Inspired by the extraordinarily resilient and strong binding force of the Great Wall binder, that is, the sticky rice mortar, we extracted highly branched amylopectin (HBA), the effective ingredient, as a low‐cost, nontoxic and environmentally benign aqueous binder for the sulfur cathode. The HBA‐based cells outperform the Li‐S batteries based on the traditional polyvinyldene diflouride (PVDF) binder and a lowly branched polysaccharide binder. The improved electrochemical performance in the HBA‐based cell could be attributed to two mechanisms. First, the branched structure of the HBA provides enhanced mechanical and adhesive properties, which allow for a robust electronic and ionic conductive framework to be maintained throughout the cathode after extended cycling. Second, the HBA shows enhanced polysulfide retention due to the polymer's abundant lone‐pair rich hydroxyl groups and the formation of C─S bonds between the HBA and polysulfides prohibits the shuttle effect of polysulfides. The improved mechanical properties and polysulfide retention function of the HBA binder facilitate the HBA‐based Li‐S battery to deliver a long cycle life of 500 cycles at 2 C while only displaying a capacity fading of 0.104% per cycle.

The study aimed to quantify the clinical activity profile of physiotherapy students within a regional student-led musculoskeletal clinic. A retrospective clinical audit examined all occasions of service (OOS) delivered during 2018. Demographic data and student to clinical educator (CE) ratio were also collected. Descriptive statistics were used to describe patient demographics. The average OOS per student per week between student to CE ratios (i.e., 2:1 and 3:1 group) were analysed using a repeated measures ANOVA. A total of 214 clients were included (mean age 40.9 years (SD 20.4) with 66.5% being female (n = 133)). The shoulder (19.3%) was the most assessed/treated region, followed by the knee (18.9%), and ankle/foot (16.2%). Analysis revealed a main effect of week (p

Augmented reality (AR) has the potential to fundamentally change how people engage with increasingly interactive urban environments. However, many challenges exist in designing and evaluating these new urban AR experiences, such as technical constraints and safety concerns associated with outdoor AR. We contribute to this domain by assessing the use of virtual reality (VR) for simulating wearable urban AR experiences, allowing participants to interact with future AR interfaces in a realistic, safe and controlled setting. This paper describes two wearable urban AR applications (pedestrian navigation and autonomous mobility) simulated in VR. Based on a thematic analysis of interview data collected across the two studies, we find that the VR simulation successfully elicited feedback on the functional benefits of AR concepts and the potential impact of urban contextual factors, such as safety concerns, attentional capacity, and social considerations. At the same time, we highlight the limitations of this approach in terms of assessing the AR interface’s visual quality and providing exhaustive contextual information. The paper concludes with recommendations for simulating wearable urban AR experiences in VR.

ABSTRACT Outbreaks of emerging viral pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are a major medical challenge. There is a pressing need for antivirals that can be rapidly deployed to curb infection and dissemination. We determined the efficacy of interferon lambda-1 (IFN-λ) as a broad-spectrum antiviral agent to inhibit SARS-CoV-2 infection and reduce pathology in a mouse model of disease. IFN-λ significantly limited SARS-CoV-2 production in primary human bronchial epithelial cells in culture. Pretreatment of human lung cells with IFN-λ completely blocked infectious virus production, and treatment with IFN-λ at the time of infection inhibited virus production more than 10-fold. To interrogate the protective effects of IFN-λ in response to SARS-CoV-2 infection, transgenic mice expressing the human angiotensin-converting enzyme 2 (ACE-2) were tested. One dose of IFN-λ administered intranasally was found to reduce animal morbidity and mortality. Our study with SARS-CoV-2 also revealed a sex differential in disease outcome. Male mice had higher mortality, reflecting the more severe symptoms and mortality found in male patients infected with SARS-CoV-2. The results indicate that IFN-λ potentially can treat early stages of SARS-CoV-2 infection and decrease pathology, and this murine model can be used to investigate the sex differential documented in COVID-19. IMPORTANCE The COVID-19 pandemic has claimed millions of lives worldwide. In this report, we used a preclinical mouse model to investigate the prophylactic and therapeutic value of intranasal IFN-λ for this acute respiratory disease. Specific vaccines have been responsible for curbing the transmission of SARS-CoV-2 in developed nations. However, vaccines require time to generate and keep pace with antigenic variants. There is a need for broad-spectrum prophylactic and therapeutic agents to combat new emerging viral pathogens. Our mouse model suggests IFN-λ has clinical utility, and it reflects the well-documented finding that male COVID-19 patients manifest more severe symptoms and mortality. Understanding this sex bias is critical for considering therapeutic approaches to COVID-19.

Within the paradigm of the smart and playable city, the urban landscape and street furniture have provided a fertile platform for pragmatic and hedonic goals of urban liveability through technology augmentation. Smart street furniture has grown from being a novelty to become a common sight in metropolitan cities, co-opted for improving the efficiency of services. However, as we consider technologies that are increasingly smarter, with human-like intelligence, we navigate towards uncharted waters when discussing the consequences of their integration with the urban landscape. The implications of a new genre of street furniture embedded with artificial intelligence, where the machine has autonomy and is an active player itself, are yet to be fully understood. In this article, we analyse the evolving design of public benches along the axes of smartness and disruption to understand their qualities as playful, urban machines in public spaces. We present a concept-driven speculative design case study, as an exploration of a smart, sensing, and disruptive urban machine for playful placemaking. With the emergence of artificial intelligence, we expand on the potential of urban machines to partake an increasingly active role as co-creators of play and playful placemaking in the cities of tomorrow.

Abstract Background Despite significant anatomical variation amongst patients, cochlear implant frequency-mapping has traditionally followed a patient-independent approach. Basilar membrane (BM) length is required for patient-specific frequency-mapping, however cochlear duct length (CDL) measurements generally extend to the apical tip of the entire cochlea or have no clearly defined end-point. By characterizing the length between the end of the BM and the apical tip of the entire cochlea (helicotrema length), current CDL models can be corrected to obtain the appropriate BM length. Synchrotron radiation phase-contrast imaging has made this analysis possible due to the soft-tissue contrast through the entire cochlear apex. Methods Helicotrema linear length and helicotrema angular length measurements were performed on synchrotron radiation phase-contrast imaging data of 14 cadaveric human cochleae. On a sub-set of six samples, the CDL to the apical tip of the entire cochlea (CDLTIP) and the BM length (CDLBM) were determined. Regression analysis was performed to assess the relationship between CDLTIP and CDLBM. Results The mean helicotrema linear length and helicotrema angular length values were 1.6 ± 0.9 mm and 67.8 ± 37.9 degrees, respectively. Regression analysis revealed the following relationship between CDLTIP and CDLBM: CDLBM = 0.88(CDLTIP) + 3.71 (R 2 = 0.995). Conclusion This is the first known study to characterize the length of the helicotrema in the context of CDL measurements. It was determined that the distance between the end of the BM and the tip of the entire cochlea is clinically consequential. A relationship was determined that can predict the BM length of an individual patient based on their respective CDL measured to the apical tip of the cochlea.

Abstract Background Neuroinflammation can modulate brain development; however, the influence of an acute peripheral immune challenge on neuroinflammatory responses in the early postnatal brain is not well characterized. To address this gap in knowledge, we evaluated the peripheral and central nervous system (CNS) immune responses to a mixed immune challenge in early postnatal rats of varying strains and sex. Methods On postnatal day 10 (P10), male and female Lewis and Brown Norway rats were injected intramuscularly with either a mix of bacterial and viral components in adjuvant, adjuvant-only, or saline. Immune responses were evaluated at 2 and 5 days post-challenge. Cytokine and chemokine levels were evaluated in serum and in multiple brain regions using a Luminex multiplex assay. Multi-factor ANOVAs were used to compare analyte levels across treatment groups within strain, sex, and day of sample collection. Numbers and activation status of astrocytes and microglia were also analyzed in the cortex and hippocampus by quantifying immunoreactivity for GFAP, IBA-1, and CD68 in fixed brain slices. Immunohistochemical data were analyzed using a mixed-model regression analysis. Results Acute peripheral immune challenge differentially altered cytokine and chemokine levels in the serum versus the brain. Within the brain, the cytokine and chemokine response varied between strains, sexes, and days post-challenge. Main findings included differences in T helper (Th) type cytokine responses in various brain regions, particularly the cortex, with respect to IL-4, IL-10, and IL-17 levels. Additionally, peripheral immune challenge altered GFAP and IBA-1 immunoreactivity in the brain in a strain- and sex-dependent manner. Conclusions These findings indicate that genetic background and sex influence the CNS response to an acute peripheral immune challenge during early postnatal development. Additionally, these data reinforce that the developmental time point during which the challenge occurs has a distinct effect on the activation of CNS-resident cells.