Catenary "Best Fit"

Catenary curves are often seen in architecture and in suspension bridges. In the following article, the process of “fitting” a curve to the St. Louis arch is presented using dynamic geometry software (DGS) and TI-nspire graphing calculators

‘Subjects and Objects: Material Expressions of Love and Loyalty in Seventeenth-Century England’, in special section on ‘Loyalties and Allegiances in Early Modern England’ in Journal of British Studies Vol. 48: 4 (October, 2009)

This article investigates how and where the emotive relations between subject and state were forged and how these ideas were manifested in early modern England. McShane describes an affective economy of loyalty, embodied in cheap and accessible political commodities: decorated objects made of clay, metals, and paper, on which precious household resources of time, money and emotion were spent. She argues that by engendering, inculcating and insinuating codes of political love into people’s ‘emotional, sensual, representational, and communicative’ lives, ‘loyal’ goods acted as vehicles and texts for what Victoria Kahn describes as ‘the supplementary role of the passions’ in ‘forging political obligation’ and the reformulation of ‘the duty to love’ of both subject and king in 17th-century England. McShane’s research contributes to a growing theme in scholarship, namely the active consumption of politically significant goods. This essay extends the range of objects under examination to include quotidian household items, shedding light on the dissemination and construction of early modern loyalty across a much wider social scale. The research draws on an extensive survey of collections held at the V&A, the Museum of London, Ashmolean Museum, Fitzwilliam Museum and Burrell Collection. Importantly, by putting illustrated print products back together with other political commodities in the early modern home, creating a broad archive of objects and text-objects where each informs the other, McShane’s approach challenges the typical social historical methodology, which uses material culture as merely illustrative of textual sources. This article was part of a special section on loyalty and allegiance in early modern England, co-edited by McShane with Dr Ted Vallance for one of the leading scholarly journals in the field. The material was drawn from a workshop on the topic held at the University of Liverpool funded by the British Academy, University of Liverpool and the Scouloudi Foundation (2007)

Anthropometric cut-offs to identify hyperglycemia in an Afro-Caribbean population: a cross-sectional population-based study from Barbados.

INTRODUCTION: Body mass index (BMI) and waist circumference (WC) cut-offs associated with hyperglycemia may differ by ethnicity. We investigated the optimal BMI and WC cut-offs for identifying hyperglycemia in the predominantly Afro-Caribbean population of Barbados. RESEARCH DESIGN AND METHODS: A cross-sectional study of 865 individuals aged ≥25 years without known diabetes or cardiovascular disease was conducted. Hyperglycemia was defined as fasting plasma glucose ≥5.6 mmol/L or hemoglobin A1c ≥5.7% (39 mmol/mol). The Youden index was used to identify the optimal cut-offs from the receiver operating characteristic (ROC) curves. Further ROC analysis and multivariable log binomial regression were used to compare standard and data-derived cut-offs. RESULTS: The prevalence of hyperglycemia was 58.9% (95% CI 54.7% to 63.0%). In women, optimal BMI and WC cut-offs (27 kg/m2 and 87 cm, respectively) performed similarly to standard cut-offs. In men, sensitivities of the optimal cut-offs of BMI ≥24 kg/m2 (72.0%) and WC ≥86 cm (74.0%) were higher than those for standard BMI and WC obesity cut-offs (30.0% and 25%-46%, respectively), although with lower specificity. Hyperglycemia was 70% higher in men above the data-derived WC cut-off (prevalence ratio 95% CI 1.2 to 2.3). CONCLUSIONS: While BMI and WC cut-offs in Afro-Caribbean women approximate international standards, our findings, consistent with other studies, suggest lowering cut-offs in men may be warranted to improve detection of hyperglycemia. Our findings do, however, require replication in a new data set.The project was supported by the Ministry of Health of the Government of Barbados. ANW is supported by the Fogarty International Center of the National Institutes of Health under Award Number K43TW010698. This paper describes the views of the authors and does not necessarily represent the official views of the National Institutes of Health (USA)

Deliver on Your Own: Disrespectful Maternity Care in rural Kenya

Background: Under the Free Maternity Policy (FMP), Kenya has witnessed an increase in health facility deliveries rather than home deliveries with Traditional Birth Attendants (TBA) resulting in improved maternal and neonatal outcomes. Despite these gains, maternal and infant mortality and morbidity rates in Kenya remain unacceptably high indicating that more needs to be done. Aim: Using data from the Access to Quality Care through Extending and Strengthening Health Systems (AQCESS) project’s qualitative gender assessment, this paper examines women’s experience of disrespectful care during pregnancy, labour, and delivery. The goal is to promote an improved understanding of the actual care conditions to inform the development of interventions that can lift the standard of care, increase maternity facility use, and improve health outcomes for both women and newborns. Methodology: We conducted sixteen focus group discussions (FGDs), two each for adolescent females, adult females, adult males, and community health committee members. As well, twenty-four key Informants interviews (KII) were also conducted including religious leaders, and persons from local government representatives, Ministry of Health (MOH), and local women’s organizations. Data were captured through audio recordings and reflective field notes. Research site: Kisii and Kilifi Counties in Kenya. Findings: Findings show nursing and medical care during labour and delivery were at times disrespectful, humiliating, uncompassionate, neglectful, or abusive. In both counties, male health workers were preferred by women giving birth, as they were perceived as more friendly and sensitive. Adolescent females were more likely to report abuse during maternity care while women with disabled children reported being stigmatized. Structural barriers related to transportation and available resources at facilities associated with disrespectful care were identified. Conclusions: A focus on quality and compassionate care as well as more facility resources will lead to increased, successful, and sustainable use of facility care. Interpreting these results within a systems perspective, Kenya needs to implement, enforce, and monitor quality of care guidelines for pregnancy and delivery including respectful maternity care of pregnant women. To ensure these procedures are enforced, measurable benchmarks for maternity care need to be established, and hospitals need to be regularly monitored to ensure these benchmarks are achieved

Mathematical modelling of human P2X-mediated plasma membrane electrophysiology and calcium dynamics in microglia

Regulation of cytosolic calcium (Ca2+) dynamics is fundamental to microglial function. Temporal and spatial Ca2+ fluxes are induced from a complicated signal transduction pathway linked to brain ionic homeostasis. In this paper, we develop a novel biophysical model of Ca2+ and sodium (Na+) dynamics in human microglia and evaluate the contribution of purinergic receptors (P2XRs) to both intracellular Ca2+ and Na+ levels in response to agonist/ATP binding. This is the first comprehensive model that integrates P2XRs to predict intricate Ca2+ and Na+ transient responses in microglia. Specifically, a novel compact biophysical model is proposed for the capture of whole-cell patch-clamp currents associated with P2X4 and P2X7 receptors, which is composed of only four state variables. The entire model shows that intricate intracellular ion dynamics arise from the coupled interaction between P2X4 and P2X7 receptors, the Na+/Ca2+ exchanger (NCX), Ca2+ extrusion by the plasma membrane Ca2+ ATPase (PMCA), and Ca2+ and Na+ leak channels. Both P2XRs are modelled as two separate adenosine triphosphate (ATP) gated Ca2+ and Na+ conductance channels, where the stoichiometry is the removal of one Ca2+ for the hydrolysis of one ATP molecule. Two unique sets of model parameters were determined using an evolutionary algorithm to optimise fitting to experimental data for each of the receptors. This allows the proposed model to capture both human P2X7 and P2X4 data (hP2X7 and hP2X4). The model architecture enables a high degree of simplicity, accuracy and predictability of Ca2+ and Na+ dynamics thus providing quantitative insights into different behaviours of intracellular Na+ and Ca2+ which will guide future experimental research. Understanding the interactions between these receptors and other membrane-bound transporters provides a step forward in resolving the qualitative link between purinergic receptors and microglial physiology and their contribution to brain pathology

Support for healthy breastfeeding mothers with healthy term babies

BACKGROUND: There is extensive evidence of important health risks for infants and mothers related to not breastfeeding. In 2003, the World Health Organization recommended that infants be breastfed exclusively until six months of age, with breastfeeding continuing as an important part of the infant's diet until at least two years of age. However, current breastfeeding rates in many countries do not reflect this recommendation. OBJECTIVES: To describe forms of breastfeeding support which have been evaluated in controlled studies, the timing of the interventions and the settings in which they have been used.To examine the effectiveness of different modes of offering similar supportive interventions (for example, whether the support offered was proactive or reactive, face-to-face or over the telephone), and whether interventions containing both antenatal and postnatal elements were more effective than those taking place in the postnatal period alone.To examine the effectiveness of different care providers and (where information was available) training.To explore the interaction between background breastfeeding rates and effectiveness of support. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (29 February 2016) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing extra support for healthy breastfeeding mothers of healthy term babies with usual maternity care. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: This updated review includes 100 trials involving more than 83,246 mother-infant pairs of which 73 studies contribute data (58 individually-randomised trials and 15 cluster-randomised trials). We considered that the overall risk of bias of trials included in the review was mixed. Of the 31 new studies included in this update, 21 provided data for one or more of the primary outcomes. The total number of mother-infant pairs in the 73 studies that contributed data to this review is 74,656 (this total was 56,451 in the previous version of this review). The 73 studies were conducted in 29 countries. Results of the analyses continue to confirm that all forms of extra support analyzed together showed a decrease in cessation of 'any breastfeeding', which includes partial and exclusive breastfeeding (average risk ratio (RR) for stopping any breastfeeding before six months 0.91, 95% confidence interval (CI) 0.88 to 0.95; moderate-quality evidence, 51 studies) and for stopping breastfeeding before four to six weeks (average RR 0.87, 95% CI 0.80 to 0.95; moderate-quality evidence, 33 studies). All forms of extra support together also showed a decrease in cessation of exclusive breastfeeding at six months (average RR 0.88, 95% CI 0.85 to 0.92; moderate-quality evidence, 46 studies) and at four to six weeks (average RR 0.79, 95% CI 0.71 to 0.89; moderate quality, 32 studies). We downgraded evidence to moderate-quality due to very high heterogeneity.We investigated substantial heterogeneity for all four outcomes with subgroup analyses for the following covariates: who delivered care, type of support, timing of support, background breastfeeding rate and number of postnatal contacts. Covariates were not able to explain heterogeneity in general. Though the interaction tests were significant for some analyses, we advise caution in the interpretation of results for subgroups due to the heterogeneity. Extra support by both lay and professionals had a positive impact on breastfeeding outcomes. Several factors may have also improved results for women practising exclusive breastfeeding, such as interventions delivered with a face-to-face component, high background initiation rates of breastfeeding, lay support, and a specific schedule of four to eight contacts. However, because within-group heterogeneity remained high for all of these analyses, we advise caution when making specific conclusions based on subgroup results. We noted no evidence for subgroup differences for the any breastfeeding outcomes. AUTHORS' CONCLUSIONS: When breastfeeding support is offered to women, the duration and exclusivity of breastfeeding is increased. Characteristics of effective support include: that it is offered as standard by trained personnel during antenatal or postnatal care, that it includes ongoing scheduled visits so that women can predict when support will be available, and that it is tailored to the setting and the needs of the population group. Support is likely to be more effective in settings with high initiation rates. Support may be offered either by professional or lay/peer supporters, or a combination of both. Strategies that rely mainly on face-to-face support are more likely to succeed with women practising exclusive breastfeeding

Spatially- and temporally-controlled postnatal p53 knockdown cooperates with embryonic Schwann cell precursor Nf1 gene loss to promote malignant peripheral nerve sheath tumor formation

Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive sarcomas that arise sporadically or in association with the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. In individuals with NF1, MPNSTs are hypothesized to arise from Nf1-deficient Schwann cell precursor cells following the somatic acquisition of secondary cooperating genetic mutations (e.g., p53 loss). To model this sequential genetic cooperativity, we coupled somatic lentivirus-mediated p53 knockdown in the adult right sciatic nerve with embryonic Schwann cell precursor Nf1 gene inactivation in two different Nf1 conditional knockout mouse strains. Using this approach, ~60% of mice with Periostin-Cre-mediated Nf1 gene inactivation (Periostin-Cre; Nf1(flox/flox) mice) developed tumors classified as low-grade MPNSTs following p53 knockdown (mean, 6 months). Similarly, ~70% of Nf1+/- mice with GFAP-Cre-mediated Nf1 gene inactivation (GFAP-Cre; Nf1(flox/null) mice) developed low-grade MPNSTs following p53 knockdown (mean, 3 months). In addition, wild-type and Nf1+/- mice with GFAP-Cre-mediated Nf1 loss develop MPNSTs following somatic p53 knockout with different latencies, suggesting potential influences of Nf1+/- stromal cells in MPNST pathogenesis. Collectively, this new MPNST model system permits the analysis of somatically-acquired events as well as tumor microenvironment signals that potentially cooperate with Nf1 loss in the development and progression of this deadly malignancy

Integrative genomic analysis reveals low T-cell infiltration as the primary feature of tobacco use in HPV-positive oropharyngeal cancer

Although tobacco use is an independent adverse prognostic feature in HPV(+) oropharyngeal squamous cell carcinoma (OPSCC), the biologic features associated with tobacco use have not been systematically investigated. We characterized genomic and immunologic features associated with tobacco use through whole exome sequencing, mRNA hybridization, and immunohistochemical staining in 47 HPV(+) OPSCC tumors. Low expression of transcripts in a T cell-inflamed gene expression profile (TGEP) was associated with tobacco use at diagnosis and lower overall and disease-free survival. Tobacco use was associated with an increased proportion of T \u3e C substitutions and a lower proportion of expected mutational signatures, but not with increases in mutational burden or recurrent oncogenic mutations. Our findings suggest that rather than increased mutational burden, tobacco\u27s primary and clinically relevant association in HPV(+) OPSCC is immunosuppression of the tumor immune microenvironment. Quantitative assays of T cell infiltration merit further study as prognostic markers in HPV(+) OPSCC