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Motivated by the ABO issue of the blood bank system, in which the portions stored have constant shelf life, we consider two subsystems of perishable inventory. The two Perishable Inventory Subsystems-PIS A and PIS B, are correlated to each other through a one-way substitution of demands. Specifically, the input streams and the demand streams applied to each subsystem are four Poisson processes, which are independent of one another. However, if the shelf of PIS A (blood of type O) is empty of items, an arriving demand of type A is unsatisfied, since demand of type A cannot be satisfied by an item of type B (blood portions of type AB), but if the shelf of PIS B is empty of items, an arriving demand of type B is applied to PIS A, since demands of type B can be satisfied by both types. This one-way substitution of the issuing policy generates for PIS A a modulated Poisson demand process operating in a two-state non-Markovian environment. The performance analysis of PIS B is known from previous work. Thus, in this study we focus on the marginal performance analysis of PIS A. Based on a fluid formulation and a Markovian approximation for the one-way substitution demand process, we develop a unified approach to efficiently and accurately approximate the performance of the PIS A. The effectiveness of the approach is investigated by extensive numerical experiments.

Pentecostalism and politics are, for better or worse, no strangers. In 2018, Scott Morrison became the first pentecostal prime minister in the history of Australia and, possibly, in the English-speaking world. He then led the Liberal Party to a resounding election victory in 2019. As a result, Morrison was dubbed the “Miracle Man” after his acceptance speech referred to divine intervention in the electoral results. Since then, there has been regular, negative speculation on links between Morrison’s pentecostal faith and policy positions. This article provides a counterposition that several elements of the pentecostal worldview have the potential for positive impact in politics and may explain aspects of Morrison’s electoral success. We argue that Morrison effectively leveraged his pentecostal experience and convictions to advantage through strong leadership, practical pragmatism, marketing acumen, and a narrative of hope. Here, in a morass of indecision and “policy-free” political elites, was someone who believed in something.

Background: Well-conducted peer observation of teaching (POT) can be an effective tool in enhancing teaching quality and educator development in healthcare teaching including dentistry. Experience suggests that its effectiveness depends on the environment in which it is undertaken. A previous study investigated engagement with POT by a dental school faculty in the UK and identified barriers to its routine use for educator development. These barriers are particularly problematic for part-time educators who play an increasingly significant, but frequently underestimated role, in undergraduate dental teaching, complementing the teaching of full-time clinical academics. Owing to the part-time nature of their roles, opportunities for their teaching development are limited. This can lead to dissatisfaction and a lack of fulfillment, and ultimately their loss from teaching faculty. Aims: This study explores POT’s utility for the development of part-time dental educators’ (PTDEs). Specifically it (i) audited their engagement with POT, (ii) reviewed the design(s) employed, (iii) assessed participant’s perceived value of it and (iv) explored methods to maximize its utility for their teaching development. Method: Teaching roles and experience, current engagement and experience of POT of part-time educators employed in a UK dental school were explored using a mixed methodology survey. Free-text responses were subjected to thematic analysis and emerging themes were subsequently explored iteratively by undertaking observations of seven part-time educators in various dental teaching environments. A developmental POT approach was used to assess utility. Results: Of 44 surveys distributed, 27 (61%) completed surveys were returned. 24 (89%) respondents reported that POT was of some or high value and resulted in enhanced teaching quality. Respondents experienced difficulties undertaking POT annually with only 14 (52%) achieving this. Observer choice emerged as fundamental to its utility. Additionally, the study identified a number of barriers to its effective use.

We examine the association between trauma patterns, gender identity, ethnicity, foster care involvement, and mental health needs in a sample of low-income youth. Our community sample included 2,175 clients aged 6 or older (M

We study the busy period of a single server queueing systemoperating in two alternating modes - working and vacation. In the two modes the systems run as an MX/G/1 queue with disasters, but with different parameters. The vacation mode starts once the number of customers drops to zero. It is terminated randomly (when it is not empty) with a transition to the working mode. At such a transition moment all the customers are transferred to the working mode; the service of the customer being served is lost and it starts from scratch in the working mode. Every busy period starts with a batch arrival into an empty system and terminates at the first time that the number of customers drops to zero. The working and the vacation periods are analyzed too. Finally, we apply the results to obtain the probability generating functions of the number of customers in the working, as well as in the vacation periods.

Background: People with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) daily experience core symptoms of post-exertional malaise, unrefreshing sleep, and cognitive impairment or brain fog. Despite numbering 0.2-0.4% of the population, no laboratory test is available for their diagnosis, no effective therapy exists for their treatment, and no scientific breakthrough regarding their pathogenesis has been made. It remains unknown, despite decades of small-scale studies, whether individuals experience different types of ME/CFS separated by onset-type, sex or age. Methods: DecodeME is a large population-based study of ME/CFS that recruited 17,074 participants in the first 3 months following full launch. Their detailed questionnaire responses provided an unparalleled opportunity to investigate illness severity, onset, course and duration. Results: The well-established sex-bias among ME/CFS patients is evident in the initial DecodeME cohort: 83.5% of participants were females. What was not known previously was that females’ comorbidities and symptoms tend to be more numerous than males’. Moreover, being female, being older and being over 10 years from ME/CFS onset are significantly associated with greater severity. Five different ME/CFS onset types were examined in the self-reported data: those with ME/CFS onset (i) after glandular fever (infectious mononucleosis); (ii) after COVID-19 infection; (iii) after other infections; (iv) without an identified infectious onset; and, (v) where the occurrence of an infection at or preceding onset is not known. Conclusions: This revealed that people with a ME/CFS diagnosis are not a homogeneous group, as clear differences exist in symptomatology and comorbidity.

The musculoskeletal (MSK) system begins to form in the third week of intrauterine development. Multiple genes are involved in the complex different processes to form the skeleton, muscles and joints. The embryonic period, from the third to the eighth week of development, is critical for normal development and therefore the time when most structural defects are induced. Many of these defects have a genetic origin, but environmental factors may also play a very important role. This review summarizes the embryology of the different components of the MSK system and their configuration as an organ-system, analyzes the clinical implications resulting from failures in the process of organogenesis, and describes the first approach to diagnosis of skeletal abnormalities using prenatal ultrasound., SCOPUS: ar.j, info:eu-repo/semantics/published

Background Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a common, long-term condition characterised by post-exertional malaise, often with fatigue that is not significantly relieved by rest. ME/CFS has no confirmed diagnostic test or effective treatment and we lack knowledge of its causes. Identification of genes and cellular processes whose disruption adds to ME/CFS risk is a necessary first step towards development of effective therapy. Methods Here we describe DecodeME, an ongoing study co-produced by people with lived experience of ME/CFS and scientists. Together we designed the study and obtained funding and are now recruiting up to 25,000 people in the UK with a clinical diagnosis of ME/CFS. Those eligible for the study are at least 16 years old, pass international study criteria, and lack any alternative diagnoses that can result in chronic fatigue. These will include 5,000 people whose ME/CFS diagnosis was a consequence of SARS-CoV-2 infection. Questionnaires are completed online or on paper. Participants’ saliva DNA samples are acquired by post, which improves participation by more severely-affected individuals. Digital marketing and social media approaches resulted in 29,000 people with ME/CFS in the UK pre-registering their interest in participating. We will perform a genome-wide association study, comparing participants’ genotypes with those from UK Biobank as controls. This should generate hypotheses regarding the genes, mechanisms and cell types contributing to ME/CFS disease aetiology. Discussion The DecodeME study has been reviewed and given a favourable opinion by the North West – Liverpool Central Research Ethics Committee (21/NW/0169). Relevant documents will be available online (www.decodeme.org.uk). Genetic data will be disseminated as associated variants and genomic intervals, and as summary statistics. Results will be reported on the DecodeME website and via open access publications.

Amyotrophic lateral sclerosis (ALS) is the most common subtype of motor neuron disease (MND). The current gold-standard measure of progression is the ALS Functional Rating Scale—Revised (ALS-FRS(R)), a clinician-administered questionnaire providing a composite score on physical functioning. Technology offers a potential alternative for assessing motor progression in both a clinical and research capacity that is more sensitive to detecting smaller changes in function. We reviewed studies evaluating the utility and suitability of these devices to evaluate motor function and disease progression in people with MND (pwMND). We systematically searched Google Scholar, PubMed and EMBASE applying no language or date restrictions. We extracted information on devices used and additional assessments undertaken. Twenty studies, involving 1275 (median 28 and ranging 6–584) pwMND, were included. Sensor type included accelerometers (n = 9), activity monitors (n = 4), smartphone apps (n = 4), gait (n = 3), kinetic sensors (n = 3), electrical impedance myography (n = 1) and dynamometers (n = 2). Seventeen (85%) of studies used the ALS-FRS(R) to evaluate concurrent validity. Participant feedback on device utility was generally positive, where evaluated in 25% of studies. All studies showed initial feasibility, warranting larger longitudinal studies to compare device sensitivity and validity beyond ALS-FRS(R). Risk of bias in the included studies was high, with a large amount of information to determine study quality unclear. Measurement of motor pathology and progression using technology is an emerging, and promising, area of MND research. Further well-powered longitudinal validation studies are needed.

This chapter explores the notion of effective communication not only in international contexts but in any situation which brings together people with diverse cultures. The chapter begins with a brief look at some intercultural experiences and then explores the notion of ‘culture' and how it can shape our behavior and patterns of thought. From there, it moves on to discuss the ‘classical view' of human interpersonal communication—and why it is incorrect—and then describes a model of communication which regards this as a ‘construction' or ‘negotiation of meaning'. The chapter continues by examining the broad concept of intercultural competence and then looks at some of the key skills, attributes and strategies which can contribute to both effective intercultural and intracultural communication. An appendix includes some example activities designed to develop greater cultural awareness.

Population aging is a defining demographic reality of our era. It is associated with an increase in the societal burden of delivering care to older adults with chronic conditions or frailty. How to integrate global population aging and technology development to help address the growing demands for care facing many aging societies is both a challenge and an opportunity for innovation. We propose a social technology approach that promotes use of technologies to assist individuals, families, and communities to cope more effectively with the disabilities of older adults who can no longer live independently due to dementia, serious mental illness, and multiple chronic health problems. The main contributions of the social technology approach include: (1) fostering multidisciplinary collaboration among social scientists, engineers, and healthcare experts; (2) including ethical and humanistic standards in creating and evaluating innovations; (3) improving social systems through working with those who deliver, manage, and design older adult care services; (4) promoting social justice through social policy research and innovation, particularly for disadvantaged groups; (5) fostering social integration by creating age-friendly and intergenerational programs; and (6) seeking global benefit by identifying and generalizing best practices. As an emergent, experimental approach, social technology requires systematic evaluation in an iterative process to refine its relevance and uses in different local settings. By linking technological interventions to the social and cultural systems of older people, we aim to help technological advances become an organic part of the complex social world that supports and sustains care delivery to older adults in need.

Scanning ion conductance microscopy (SICM) is a powerful and versatile technique that allows an increasingly wide range of interfacial properties and processes to be studied. SICM employs a nanopipette tip that contains electrolyte solution and a quasi-reference counter electrode (QRCE), to which a potential is applied with respect to a QRCE in a bathing solution, in which the tip is placed. The work herein considers the potential-controlled delivery of uncharged electroactive molecules (solute) from an SICM tip to a working electrode substrate to determine the effect of the substrate on electroosmotic flow (EOF). Specifically, the local delivery of hydroquinone from the tip to a carbon fiber ultramicroelectrode (CF UME) provides a means of quantifying the rate of mass transport from the nanopipette and mapping electroactivity via the CF UME current response for hydroquinone oxidation to benzoquinone. EOF, and therefore species delivery, has a particularly strong dependence on the charge of the substrate surface at close nanopipette-substrate surface separations, with implications for retaining neutral solute within the tip predelivery and for the delivery process itself, both controlled via the applied tip potential. Finite element method (FEM) simulations of mass transport and reactivity are used to explain the experimental observations and identify the nature of EOF, including unusual flow patterns under certain conditions. The combination of experimental results with FEM simulations provides new insights on mass transport in SICM that will enhance quantitative applications and enable new possibilities for the use of nanopipettes for local delivery.

The present research examined whether temporal fluctuations in context ethnic diversity account for current levels of implicit ethnic-American associations. Temporal fluctuations in ethnic diversity at the metropolitan level were assessed using data from four decennial U.S. censuses (1980–2010) and distinguishing three dimensions of context ethnic diversity (minority representation, variety, and integration). Project Implicit data (2011–2017) indexed the extent to which American identity was implicitly associated with European Americans over Asian Americans (i.e., American = White associations). Data were analyzed using multilevel modeling ( N = 152,011, nested within 226 metropolitan areas). Steeper increases in the proportion of Asian Americans were related to weaker implicit (but stronger explicit) American = White associations. Increases in ethnic integration accounted for stronger implicit American = White associations when integration fluctuations reflected accelerating rather than decelerating trends. These results suggest that current levels of implicit ethnic-national associations are linked to complex patterns of ethnic diversity fluctuations.

The SARS-CoV-2 pandemic revealed the fragility of global supply chains, resulting in shortages of essential clinical supplies for the detection and treatment of COVID-19, including nasopharyngeal swabs (NP) commonly used to collect clinical samples for respiratory disease diagnostics. Groups around the world led a response to find alternatives to these shortages. Here, we describe the development of a single-component nasopharyngeal swab (GrooveSwab) composed of medical grade polypropylene that can be mass manufactured using conventional injection molding. The design inspired by cat tongue papillae consists of a non-absorbent stacked ring structure that allows for efficient and comfortable collection of viscous mucus samples and faster release into collection medium compared to traditional absorbent swabs. GroveSwabs were evaluated in 2 clinical studies in the US and Peru and demonstrated 90% or better concordance with commercial swabs. The simplified NP swab offers a reliable, lower cost, and more manufacturable alternative to absorbent swabs to avoid future shortages.

Stroke is a leading medical issue that can impact the person’s ability to walk effectively. There is limited research into the design and biomechanical response for exosuits that assist more proximal joints such as the hip. For this case series, three subjects with chronic stroke participated in a single-session study to evaluate hip flexion exosuit assistance in overground walking. We iteratively tuned the unilateral hip flexion assistance profiles in overground gait. Compared to the initial unpowered baseline, walking speed at the end of tuning and with the device powered increased for 2 of 3 individuals and on average by 0.16 m s\(^{-1}\). We then compared powered versus unpowered overground walking during a 5 min evaluation period. Circumduction was reduced by 9 \(\pm 1\) mm and cost of transport was reduced by 8.6 \(\pm 1.7\)% for the 3 participants.

Since the widespread introduction of the conjugate pneumococcal vaccine and subsequent decline of invasive pneumococcal disease in children, a significant proportion of children with pneumococcal meningitis are identified as having an underlying immunodeficiency or predisposing anatomic abnormality. We present 3 cases of recurrent pneumococcal meningitis where detailed neuro-imaging revealed subtle anterior base of skull defects not detected on initial investigations.

Lowering locomotion's metabolic cost Walking and running require different gaits, with each type of motion putting a greater bias on different muscles and joints. Kim et al. developed a soft, fully portable, lightweight exosuit that is able to reduce the metabolic rate for both running and walking by assisting each motion via the hip extension (see the Perspective by Pons). A waist belt holds most of the mass, thus reducing the cost of carrying the suit. By tracking the motion of the user, the suit is able to switch modes between the two types of motion automatically. Science , this issue p. 668 ; see also p. 636

The surface charge and topography of human hair are visualized synchronously at the nanoscale using scanning ion conductance microscopy (SICM), a scanning nanopipette probe technique that uses local ion conductance currents to image the physicochemical properties of interfaces. By combining SICM data with finite element method (FEM) simulations that solve for ion transport at the nanopipette under bias, one is able to quantitatively correlate colocated surface charge and topography. The hair samples studied herein, from a 25-year-old Caucasian male with light hair (as an exemplar), reveal that untreated hair, in areas ca. 1 cm from the root, has a fairly uniform negative charge density of ca. −15 mC/cm–2 (in pH 6.8 aqueous solution), with some higher magnitude negative values localized near the boundaries between hair cuticles. Common chemical treatments result in varying degrees of charge heterogeneity. A bleach treatment produces some highly negatively charged localized regions (−80 to −100 mC/cm–2 at p...

Scanning ion conductance microscopy (SICM) is becoming a powerful multifunctional tool for probing and analyzing surfaces and interfaces. This work outlines methodology for the quantitative controlled delivery of ionic redox-active molecules from a nanopipette to a substrate electrode, with a high degree of spatial and temporal precision. Through control of the SICM bias applied between a quasi-reference counter electrode (QRCE) in the SICM nanopipette probe and a similar electrode in bulk solution, it is shown that ionic redox species can be held inside the nanopipette, and then pulse-delivered to a defined region of a substrate positioned beneath the nanopipette. A self-referencing hopping mode imaging protocol is implemented, where reagent is released in bulk solution (reference measurement) and near the substrate surface at each pixel in an image, with the tip and substrate currents measured throughout. Analysis of the tip and substrate current data provides an improved understanding of mass transport and nanoscale delivery in SICM and a new means of synchronously mapping electrode reactivity, surface topography, and charge. Experiments on Ru(NH3)63+ reduction to Ru(NH3)62+ and dopamine oxidation in aqueous solution at a carbon fiber ultramicroelectrode (UME), used as the substrate, illustrate these aspects. Finite element method (FEM) modeling provides quantitative understanding of molecular delivery in SICM. The approach outlined constitutes a new methodology for electrode mapping and provides improved insights on the use of SICM for controlled delivery to interfaces generally.

Outer-sphere electron transfer (OS-ET) is a cornerstone elementary electrochemical reaction, yet microscopic understanding is largely based on idealized theories, developed in isolation from experiments that themselves are often close to the kinetic (diffusion) limit. Focusing on graphene as-grown on a copper substrate as a model 2D material/metal-supported electrode system, this study resolves the key electronic interactions in OS-ET, and identifies the role of graphene in modulating the electronic properties of the electrode/electrolyte interface. An integrated experimental-theoretical approach combining co-located multi-microscopy, centered on scanning electrochemical cell microscopy (SECCM), with Raman microscopy and field emission-scanning electron microscopy, together with rate theory and density functional theory (DFT) calculations is used to address OS-ET kinetics of hexaamineruthenium (III/II) chloride, [Ru(NH3)6]3+/2+. The experimental methodology allows spatially-resolved electrochemical measurements to be targeted at distinct regions of monolayer, bilayer and multilayer graphene on copper, with high diffusion rates, to reveal ET kinetics in the order: monolayer > bilayer > multilayer. To rationalize these findings we extended the Schmickler-Newns-Anderson model Hamiltonian for electron transfer and parametrized it using constant potential DFT. Combining this model with rate theory reveals that the difference in kinetics at monolayer and bilayer graphene can be rationalized in the context of a dominantly adiabatic mechanism, where the addition of subsequent graphene layers increases the contact potential, producing an increase in the effective barrier to electron transfer. This study provides a roadmap for the integration of experiments, theory, and simulations in order to understand the nature of heterogeneous electron transfer at complex nanostructured electrode materials.

2D electrode materials are often deployed on conductive supports for electrochemistry and there is a great need to understand fundamental electrochemical processes in this electrode configuration. Here, an integrated experimental-theoretical approach is used to resolve the key electronic interactions in outer-sphere electron transfer (OS-ET), a cornerstone elementary electrochemical reaction, at graphene as-grown on a copper electrode. Using scanning electrochemical cell microscopy, and co-located structural microscopy, the classical hexaamineruthenium (III/II) couple shows the ET kinetics trend: monolayer > bilayer > multilayer graphene. This trend is rationalized quantitatively through the development of rate theory, using the Schmickler-Newns-Anderson model Hamiltonian for ET, with the explicit incorporation of electrostatic interactions in the double layer, and parameterized using constant potential density functional theory calculations. The ET mechanism is predominantly adiabatic; the addition of subsequent graphene layers increases the contact potential, producing an increase in the effective barrier to ET at the electrode/electrolyte interface., This combined experimental and theoretical study reveals the nature of electron transfer at graphene as grown on copper. The authors find that outer-sphere electron transfer occurs adiabatically with slower kinetics for multi- than for monolayer graphene.

Despite the ambiguity inherent in the terms ‘research’ and ‘scholarship’, both continue to play an important role in higher education in terms of regulatory requirements, measuring institutional achievement, and investment of time and other resources. It is often left to individual institutions and various interest groups to define their own understanding of the connection between the two. For Christian higher education providers with limited resources, a lack of government funding and a focus on broader community dissemination, scholarship has often taken precedence over research. Using an Australian case study, this chapter argues that a holistic understanding of both research and scholarship, and the relation between them, helps to orient institutional efforts towards positive impact and engagement for constituents and end-users.

Objective: Children frequently present with head injuries to acute care settings. Although international paediatric clinical practice guidelines for head injuries exist, they do not address all considerations related to triage, imaging, observation versus admission, transfer, discharge and follow-up of mild to moderate head injuries relevant to the Australian and New Zealand context. The Paediatric Research in Emergency Departments International Collaborative (PREDICT) set out to develop an evidence-based, locally applicable, practical clinical guideline for the care of children with mild to moderate head injuries presenting to acute care settings. Methods: A multidisciplinary Guideline Working Group (GWG) developed 33 questions in three key areas – triage, imaging and discharge of children with mild to moderate head injuries presenting to acute care settings. We identified existing high-quality guidelines and from these guidelines recommendations were mapped to clinical questions. Updated literature searches were undertaken, and key new evidence identified. Recommendations were created through either adoption, adaptation or development of de novo recommendations. The guideline was revised after a period of public consultation. Results: The GWG developed 71 recommendations (evidence-informed = 35, consensus-based = 17, practice points = 19), relevant to the Australian and New Zealand setting. The guideline is presented as three documents: (i) a detailed Full Guideline summarising the evidence underlying each recommendation; (ii) a Guideline Summary; and (iii) a clinical Algorithm: Imaging and Observation Decision-making for Children with Head Injuries. Conclusions: The PREDICT Australian and New Zealand Guideline for Mild to Moderate Head Injuries in Children provides high-level evidence and practical guidance for front line clinicians.

This paper reports on the use of scanning ion conductance microscopy (SICM) to locally map the ionic properties and charge environment of two live bacterial strains: the Gram-negative Escherichia coli and the Gram-positive Bacillus subtilis. SICM results find heterogeneities across the bacterial surface and significant differences among the Gram-positive and Gram-negative bacteria. The bioelectrical environment of the B. subtilis was found to be considerably more negatively charged compared to E. coli. SICM measurements, fitted to a simplified finite element method (FEM) model, revealed surface charge values of -80 to -140 mC m-2 for the Gram-negative E. coli. The Gram-positive B. subtilis show a much higher conductivity around the cell wall, and surface charge values between -350 and -450 mC m-2 were found using the same simplified model. SICM was also able to detect regions of high negative charge near B. subtilis, not detected in the topographical SICM response and attributed to the extracellular polymeric substance. To further explore how the B. subtilis cell wall structure can influence the SICM current response, a more comprehensive FEM model, accounting for the physical properties of the Gram-positive cell wall, was developed. The new model provides a more realistic description of the cell wall and allows investigation of the relation between its key properties and SICM currents, building foundations to further investigate and improve understanding of the Gram-positive cellular microenvironment.

By characterizing the trajectories of antibiotic resistance gene transfer in bacterial communities such as the gut microbiome, we will better understand the factors that influence this spread of resistance. Our aim was to investigate the host network of a multi-drug resistance broad-host-range plasmid in the culturable gut microbiome of zebrafish. This was done throughin vitroandin vivoconjugation experiments withEscherichia colias donor of the plasmid pB10::gfp. When this donor was mixed with the extracted gut microbiome, only transconjugants ofAeromonas veroniiwere detected. In separate matings between the same donor and four prominent isolates from the gut microbiome, the plasmid transferred to two of these four isolates,A. veronii and Plesiomonas shigelloides,but not toShewanella putrefaciensandVibrio mimicus. When theseA. veronii and P. shigelloidestransconjugants were the donors in matings with the same four isolates, the plasmid now also transferred fromA. veroniitoS. putrefaciens.P. shigelloideswas unable to donate the plasmid andV. mimicuswas unable to acquire it. Finally, when theE. colidonor was addedin vivoto zebrafish through their food, plasmid transfer was observed in the gut but only toAchromobacter sp.,a rare member of the gut microbiome. This work shows that the success of plasmid-mediated antibiotic resistance spread in a gut microbiome depends on the donor-recipient species combinations and therefore their spatial arrangement. It also suggests that rare gut microbiome members should not be ignored as potential reservoirs of multi-drug resistance plasmids from food.ImportanceTo understand how antibiotic resistance plasmids end up in human pathogens it is crucial to learn how, where and when they are transferred and maintained in members of bacterial communities such as the gut microbiome. To gain insight into the network of plasmid-mediated antibiotic resistance sharing in the gut microbiome, we investigated the transferability and maintenance of a multi-drug resistance plasmid among the culturable bacteria of the zebrafish gut. We show that the success of plasmid-mediated antibiotic resistance spread in a gut microbiome can depend on which species are involved, as some are important nodes in the plasmid-host network and others dead-ends. Our findings also suggest that rare gut microbiome members should not be ignored as potential reservoirs of multi-drug resistance plasmids from food.

This paper reports on the use of scanning ion conductance microscopy (SICM) to locally map the ionic properties and charge environment of two live bacterial strains: the gramnegative Escherichia coli and the gram-positive Bacillus subtilis. SICM results find heterogeneities across the bacterial surface, and significant differences among the grampositive and -negative bacteria. The bioelectrical environment of the B. subtilis was found to be considerably more negatively charged compared to E. coli. SICM measurements, fitted to a simplified finite element method (FEM) model, revealed surface charge values of −80 to −140 mC m−2 for the gram-negative E. coli. The gram-positive B. subtilis show a much higher conductivity around the cell wall, and surface charge values between −350 and −450 mC m−2 were found using the same simplified model. SICM was also able to detect regions of high negative charge near B. subtilis, not detected in the topographical SICM response and attributed to extracellular polymeric substance. To further explore how the B. subtilis cell wall structure can influence the SICM current response, a more comprehensive FEM model, accounting for the physical properties of the gram-positive cell wall, was developed. The new model provides a more realistic description of the cell wall and allowed investigation of the relation between its key properties and SICM currents, building foundations to further investigate and improve understanding of the gram-positive cellular microenvironment.Abstract Figure

The purpose of this document is to guide ultrasound practitioners in providing accurate information on the assessment of gestational age, viability and fetal development in the first trimester. In the presence of twins and higher order multiple pregnancies, it is also intended to assess chorionicity and amnionicity which have implications for risk assessment and continuing antenatal care. This guideline has been adopted by the ASUM Council and is applicable to all ultrasound practitioners.

Canada’s post-war international policy has been deeply shaped by atlanticism – a multi-faceted connection to NATO. The Alliance has, of course, afforded Canada core protections and these considerat...

Background Stereotactic body radiotherapy (SBRT) is an emerging treatment option for liver metastases in patients unsuitable for surgery. We investigated factors associated with clinical outcomes for liver metastases treated with SBRT from a multi-center, international patient registry. Methods Patients with liver metastases treated with SBRT were identified in the RSSearch® Patient Registry. Patient, tumor and treatment characteristics associated with treatment outcomes were assessed. Dose fractionations were normalized to BED10. Overall survival (OS) and local control (LC) were evaluated using Kaplan Meier analysis and log-rank test. Results The study included 427 patients with 568 liver metastases from 25 academic and community-based centers. Median age was 67 years (31–91 years). Colorectal adenocarcinoma (CRC) was the most common primary cancer. 73% of patients received prior chemotherapy. Median tumor volume was 40 cm3 (1.6–877 cm3), median SBRT dose was 45 Gy (12–60 Gy) delivered in a median of 3 fractions [1–5]. At a median follow-up of 14 months (1–91 months) the median overall survival (OS) was 22 months. Median OS was greater for patients with CRC (27 mo), breast (21 mo) and gynecological (25 mo) metastases compared to lung (10 mo), other gastro-intestinal (GI) (18 mo) and pancreatic (6 mo) primaries (p

Electrochemical techniques, such as electrochemical impedance spectroscopy (EIS), are widely applied to probe dynamic processes across a range of systems including lithium-ion batteries (LIBs). Key questions remain on how different degradation phenomena effect the processes that allow LIB to function. One of the key processes that determines the response of batteries is the mass transport, particularly the transport of Lithium within the constituent electrode materials. This study considers mass transport within LIBs, and the extent to which electrochemical techniques, particularly EIS, can be used to meaningfully probe mass transport in LIBs with the aim to serve as a guide for future studies that wish to track changes in mass transport as batteries age and degrade. Herein, the benefits of using EIS compared to the Galvanostatic Intermittent Titration Technique (GITT) are demonstrated using well defined finite element method (FEM) simulations as the basis. Distribution of Relaxation Times was then applied to assign and map battery electrochemical processes to the EIS spectra based on their time constants. Effects such as electrode geometry, mass transport heterogeneities and the overlap between mass transport and other processes are considered and discussed with particular focus on how they affect the extraction of solid Lithium diffusion coefficients.

Monitoring crystallization in real time at the nanoscale can provide valuable new insights into the nucleation process. Herein, the application of nanopipettes as nanoreactors to study the nucleation of organic materials (pharmaceutical crystals) is demonstrated, using bicalutamide (BIC), an active pharmaceutical ingredient of the prostate cancer drug CASODEX, as a model. Crystallization is achieved using a nanoscale antisolvent system, whereby a nanopipette containing an aqueous inert salt solution is brought into contact with a dimethyl sulfoxide (DSMO) solution containing soluble BIC and the same inert salt (at the same concentration). Crystallization is driven and controlled by a combination of the applied bias between an electrode in the nanopipette and one in the bulk DMSO phase and mixing of the two solvents in the mouth of the nanopipette. Crystallization at the tip of the nanopipette causes transient blockages, as BIC particles form and translocate at the end of the nanopipette opening. At low in...

Scanning ion conductance microscopy (SICM) is a nanopipette-based scanning probe microscopy technique that utilizes the ionic current flowing between an electrode inserted inside a nanopipette probe containing electrolyte solution and a second electrode placed in a bulk electrolyte bath, to provide information on a substrate of interest. For most applications to date, the composition and concentration of the electrolyte inside and outside the nanopipette is identical, but it is shown herein that it can be very beneficial to lift this restriction. In particular, an ionic concentration gradient at the end of the nanopipette, generates an ionic current with a greatly reduced electric field strength, with particular benefits for live cell imaging. This differential concentration mode of SICM (ΔC-SICM) also enhances surface charge measurements and provides a new way to carry out reaction mapping measurements at surfaces using the tip for simultaneous delivery and sensing of the reaction rate. Comprehensive finite element method (FEM) modeling has been undertaken to enhance understanding of SICM as an electrochemical cell and to enable the interpretation and optimization of experiments. It is shown that electroosmotic flow (EOF) has much more influence on the nanopipette response in the ΔC-SICM configuration compared to standard SICM modes. The general model presented advances previous treatments, and it provides a framework for quantitative SICM studies.

The US school system is dominated by heteronormativity in the formal curriculum that gives preference to binary conceptions of sexuality. School leaders play a role in supporting or disrupting school policies facilitating or inhibiting curricular inclusion of queer content in course materials and an instructional pedagogy that promotes an equitable and inclusive educational process. Using a qualitative design and phenomenographic data analysis method, the purpose of the study was to use a queer/curriculum theory lens to explore secondary level school leaders’ perceptions about their experiences with the inclusion of queer related content in the course curricula in their schools. The sample included seven secondary level educational leaders from schools in a northeastern state in the USA. Using a qualitative design and phenomenographic data analysis methods of in-depth interviews, five categories of description of leader perceptions were identified: (1) lack of inclusion of queer content in formal ...

This paper is devoted to the performance analysis and optimization of blood testing procedures. We present a queueing model of two queues in series, representing the two stages of a blood-testing procedure. Service (testing) in stage 1 is performed in batches, whereas it is done individually in stage 2. Since particular elements of blood can only be stored and used within a finite time window, the sojourn time of blood units in the system of two queues in series is an important performance measure, which we study in detail. We also introduce a profit objective function, taking into account blood acquisition and screening costs as well as profits for blood units, which were found uncontaminated and were tested fast enough. We optimize that profit objective function w.r.t. the batch size and the length of the time window.

We consider a continuous review (s, S) model of perishable items with lost sales. Once items are perished the entire inventory drops instantaneously to zero. The total cost includes the cost of: ordering, unsatisfied demand, units destroyed, holding, and fixed cost of perishability. Both the time to perishability and the lead times are assumed to be exponentially distributed while two cases of demand distribution are considered: Poisson and compound Poisson with general demand sizes. We study the average cost criterion and provide computational results on the problem of finding the optimal re-order level, s, and order up-to level, S. None of the known work on the subject is as general as the model presented here. Our analysis leads to several insights on the optimal (s, S) policies for perishable items in the presence of lead times. For example, we demonstrate that the effectiveness of a heuristic that ignores perishability (and is also analyzed here) decreases with the demand variability and that the cost may either increase or decrease with this variability.

We consider the surplus of an insurance company that employs reinsurance. The reinsurer covers part of the claims, but in return it receives a certain part of the income from premiums of the insurance company. In addition, the reinsurer receives some of the dividends that are withdrawn when a certain surplus level b is reached. A special feature of our model is that both the fraction of the premium that goes to the reinsurer and the fraction of the claims covered by the reinsurer are state-dependent. We focus on five performance measures, viz., time to ruin, deficit at ruin, the dividend withdrawn until ruin, and the amount of money transferred to the reinsurer, respectively covered by the reinsurer.

Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) youth face hostile and exclusionary learning environments. A qualitative phenomenographic method involving semistructured intervie...

Alzheimer's disease (AD), including its mild cognitive impairment (MCI) phase that may or may not progress into the AD, is the most ordinary form of dementia. It is extremely important to correctly identify patients during the MCI stage because this is the phase where AD may or may not develop. Thus, it is crucial to predict outcomes during this phase. Thus far, many researchers have worked on only using a single modality of a biomarker for the diagnosis of AD or MCI. Although recent studies show that a combination of one or more different biomarkers may provide complementary information for the diagnosis, it also increases the classification accuracy distinguishing between different groups. In this paper, we propose a novel machine learning-based framework to discriminate subjects with AD or MCI utilizing a combination of four different biomarkers: fluorodeoxyglucose positron emission tomography (FDG-PET), structural magnetic resonance imaging (sMRI), cerebrospinal fluid (CSF) protein levels, and Apolipoprotein-E (APOE) genotype. The Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline dataset was used in this study. In total, there were 158 subjects for whom all four modalities of biomarker were available. Of the 158 subjects, 38 subjects were in the AD group, 82 subjects were in MCI groups (including 46 in MCIc [MCI converted; conversion to AD within 24 months of time period], and 36 in MCIs [MCI stable; no conversion to AD within 24 months of time period]), and the remaining 38 subjects were in the healthy control (HC) group. For each image, we extracted 246 regions of interest (as features) using the Brainnetome template image and NiftyReg toolbox, and later we combined these features with three CSF and two APOE genotype features obtained from the ADNI website for each subject using early fusion technique. Here, a different kernel-based multiclass support vector machine (SVM) classifier with a grid-search method was applied. Before passing the obtained features to the classifier, we have used truncated singular value decomposition (Truncated SVD) dimensionality reduction technique to reduce high dimensional features into a lower-dimensional feature. As a result, our combined method achieved an area under the receiver operating characteristic (AU-ROC) curve of 98.33, 93.59, 96.83, 94.64, 96.43, and 95.24% for AD vs. HC, MCIs vs. MCIc, AD vs. MCIs, AD vs. MCIc, HC vs. MCIc, and HC vs. MCIs subjects which are high relative to single modality results and other state-of-the-art approaches. Moreover, combined multimodal methods have improved the classification performance over the unimodal classification.

This chapter is an overview of the key aspects of defence funding in Canada, including the nature of the budgeting process. The author shows that the inability to spend allocated funds on capital spending has overlapped with a substantial increase in the availability of said funding since 2005. On current trends, the problem is likely to persist. While DND has made significant recent strides in making better use of the available funds, it is still having difficulty spending the procurement money.

Background: Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy.Methods: RESTART was a prospective, randomised, open-label, blinded-endpoint, parallel-group trial at 122 hospitals in the UK that assessed whether starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. For this prespecified subgroup analysis, consultant neuroradiologists masked to treatment allocation reviewed brain CT or MRI scans performed before randomisation to confirm participant eligibility and rate features of the intracerebral haemorrhage and surrounding brain. We followed participants for primary (recurrent symptomatic intracerebral haemorrhage) and secondary (ischaemic stroke) outcomes for up to 5 years (reported elsewhere). For this report, we analysed eligible participants with intracerebral haemorrhage according to their treatment allocation in primary subgroup analyses of cerebral microbleeds on MRI and in exploratory subgroup analyses of other features on CT or MRI. The trial is registered with the ISRCTN registry, number ISRCTN71907627.Findings: Between May 22, 2013, and May 31, 2018, 537 participants were enrolled, of whom 525 (98%) had intracerebral haemorrhage: 507 (97%) were diagnosed on CT (252 assigned to start antiplatelet therapy and 255 assigned to avoid antiplatelet therapy, of whom one withdrew and was not analysed) and 254 (48%) underwent the required brain MRI protocol (122 in the start antiplatelet therapy group and 132 in the avoid antiplatelet therapy group). There were no clinically or statistically significant hazards of antiplatelet therapy on recurrent intracerebral haemorrhage in primary subgroup analyses of cerebral microbleed presence (2 or more) versus absence (0 or 1) (adjusted hazard ratio [HR] 0·30 [95% CI 0·08–1·13] vs 0·77 [0·13–4·61]; pinteraction=0·41), cerebral microbleed number 0–1 versus 2–4 versus 5 or more (HR 0·77 [0·13–4·62] vs 0·32 [0·03–3·66] vs 0·33 [0·07–1·60]; pinteraction=0·75), or cerebral microbleed strictly lobar versus other location (HR 0·52 [0·004–6·79] vs 0·37 [0·09–1·28]; pinteraction=0·85). There was no evidence of heterogeneity in the effects of antiplatelet therapy in any exploratory subgroup analyses (all pinteraction>0·05).Interpretation: Our findings exclude all but a very modest harmful effect of antiplatelet therapy on recurrent intracerebral haemorrhage in the presence of cerebral microbleeds. Further randomised trials are needed to replicate these findings and investigate them with greater precision.Funding: British Heart Foundation.

Background: Non-invasive brain stimulation (NIBS) has been widely used to treat mild cognitive impairment (MCI). However, there exists no consensus on the best stimulation sites. Objective: To explore potential stimulation locations for NIBS treatment in patients with MCI, combining meta- and resting state functional connectivity (rsFC) analyses. Methods: The meta-analysis was conducted to identify brain regions associated with MCI. Regions of interest (ROIs) were extracted based on this meta-analysis. The rsFC analysis was applied to 45 MCI patients to determine brain surface regions that are functionally connected with the above ROIs. Results: We found that the dorsolateral prefrontal cortex (DLPFC) and inferior frontal gyrus were the overlapping brain regions between our results and those of previous studies. In addition, we recommend that the temporoparietal junction (including the angular gyrus), which was found in both the meta- and rsFC analysis, should be considered in NIBS treatment of MCI. Furthermore, the bilateral orbital prefrontal gyrus, inferior temporal gyrus, medial superior frontal gyrus, and right inferior occipital gyrus may be potential brain stimulation sites for NIBS treatment of MCI. Conclusion: Our results provide several potential sites for NIBS, such as the DLFPC and inferior frontal gyrus, and may shed light on the locations of NIBS sites in the treatment of patients with MCI.

Collecting multiple modalities of neuroimaging data on the same subject is increasingly becoming the norm in clinical practice and research. Fusing multiple modalities to find related patterns is a challenge in neuroimaging analysis. Canonical correlation analysis (CCA) is commonly used as a symmetric data fusion technique to find related patterns among multiple modalities. In CCA-based data fusion, principal component analysis (PCA) is frequently applied as a preprocessing step to reduce data dimension followed by CCA on dimension-reduced data. PCA, however, does not differentiate between informative voxels from non-informative voxels in the dimension reduction step. Sparse PCA (sPCA) extends traditional PCA by adding sparse regularization that assigns zero weights to non-informative voxels. In this study, sPCA is incorporated into CCA-based fusion analysis and applied on neuroimaging data. A cross-validation method is developed and validated to optimize the parameters in sPCA. Different simulations are carried out to evaluate the improvement by introducing sparsity constraint to PCA. Four fusion methods including sPCA+CCA, PCA+CCA, parallel ICA and sparse CCA were applied on structural and functional magnetic resonance imaging data of mild cognitive impairment subjects and normal controls. Our results indicate that sPCA significantly can reduce the impact of non-informative voxels and lead to improved statistical power in uncovering disease-related patterns by a fusion analysis.