A Philosophy of Religious Authority

The object of this study is to explore the philosophical basis of religious authority. The intent is to set forth an apology for the pre-eminence of the Christian faith according to the popularly-designated evangelical interpretation. There is recognized in the oft-repeated usage of the term evangelical within ecclesiastical circles a certain ambiguity of understanding. The purpose of its employment here is to establish a working basis with the intention that particular distinctions will become apparent in the text of the study

Alternate cyclin D1 mRNA splicing modulates P27\u3csup\u3eKlP1\u3c/sup\u3e binding and cell migration

Cyclin D1 is an important cell cycle regulator but in cancer its overexpression also increases cellular migration mediated by p27KlP1 stabilization and RhoA inhibition. Recently, a common polymorphism at the exon 4-intron 4 boundary of the human cyclin D1 gene within a splice donor region was associated with an altered risk of developing cancer. Altered RNA splicing caused by this polymorphism gives rise to a variant cyclin D1 isoform termed cyclin D1b, which has the same N-terminus as the canonical cyclin D1a isoform but a distinct C-terminus. In this study we show that these different isoforms have unique properties with regard to the cellular migration function of cyclin D1. Whereas they displayed little difference in transcriptional co-repression assays on idealized reporter genes, microarray cDNA expression analysis revealed differential regulation of genes including those that influence cellular migration. Additionally, while cyclin D1a stabilized p27KIP1 and inhibited RhoA-induced ROCK kinase activity, promoting cellular migration, cyclin D1b failed to stabilize p27KIP1 or inhibit ROCK kinase activity and had no effect on migration. Our findings argue that alternate splicing is an important determinant of the function of cyclin D1 in cellular migration

On the Properties of Plastic Ablators in Laser-Driven Material Dynamics Experiments

Radiation hydrodynamics simulations were used to study the effect of plastic ablators in laser-driven shock experiments. The sensitivity to composition and equation of state was found to be 5-10% in ablation pressure. As was found for metals, a laser pulse of constant irradiance gave a pressure history which decreased by several percent per nanosecond. The pressure history could be made more constant by adjusting the irradiance history. The impedance mismatch with the sample gave an increase o(100%) in the pressure transmitted into the sample, for a reduction of several tens of percent in the duration of the peak load applied to the sample, and structured the release history by adding a release step to a pressure close to the ablation pressure. Algebraic relations were found between the laser pulse duration, the ablator thickness, and the duration of the peak pressure applied to the sample, involving quantities calculated from the equations of state of the ablator and sample using shock dynamics.Comment: Typos fixe

Analysis of gene expression in the bovine corpus luteum through generation and characterisation of 960 ESTs

To gain new insights into gene identity and gene expression in the bovine corpus luteum (CL) a directionally cloned CL cDNA library was constructed, screened with a total CL cDNA probe and clones representing abundant and rare mRNA transcripts isolated. The 5Vterminal DNA sequence of 960 cDNA clones, composed of 192 abundant and 768 rare mRNA transcripts was determined and clustered into 351 non-redundant expressed sequence tag (EST) groups. Bioinformatic analysis revealed that 309 (88%) of the ESTs showed significant homology to existing sequences in the protein and nucleotide public databases. Several previously unidentified bovine genes encoding proteins associated with key aspects of CL function including extracellular matrix remodelling, lipid metabolism/steroid biosynthesis and apoptosis, were identified. Forty-two (12%) of the ESTs showed homology with human or with other uncharacterised ESTs, some of these were abundantly expressed and may therefore play an important role in primary CL function. Tissue-specificity and temporal CL gene expression of selected clones previously unidentified in bovine CL tissue was also examined. The most interesting finds indicated that mRNA encoding squalene epoxidase was constitutively expressed in CL tissue throughout the oestrous cycle and 7-fold down-regulated ( P < 0.05)in late luteal tissue, concomitant with the disappearance of systemic progesterone, suggesting that de novo cholesterol biosynthesis plays an important role in steroidogenesis. The mRNA encoding the growth factor, insulin-like growth factor-binding protein-related protein 1 (IGFBP-rP1), remained constant during the oestrous cycle and was 1.8-fold up-regulated ( P < 0.05) in late luteal tissue implying a role in CL regression

Team strategic philosophy: requiem for the infinite game

Deliberate accountability has arrived in the medical arena, producing an age of reward for measured performance, and belief in publicizing metrics to ensure clarity, with winning defined as hitting targets, whereby staff are incentivised by arbitrary objectives. Finite game theory declares that players are known, rules are fixed, and the objective agreed, but infinite game theory asserts that players are both known and unknown, rules are changeable, and the objective is to perpetuate the game; these standards are clearly at odds and risk real world chaos in global universal medical education and clinical outcomes and functioning. Five principles are necessary to lead an infinite game: first, a fair basis, such that sacrifices for its advancement are promoted; second, a trusting blame-free team culture and environment; third, competitors viewed as worthy rivals, rather than adversaries, promoting healthy competition; fourth, existential flexibility when faced with credible evidence; and finally, transformational leadership; including infinite game theory into healthcare planning may be difficult, but the potential rewards are surely worth the existential fight

Relationships between deprivation and duration of children's emergency admissions for breathing difficulty, feverish illness and diarrhoea in North West England: an analysis of hospital episode statistics

Background In the United Kingdom there has been a long term pattern of increases in children's emergency admissions and a substantial increase in short stay unplanned admissions. The emergency admission rate (EAR) per thousand population for breathing difficulty, feverish illness and diarrhoea varies substantially between children living in different Primary Care Trusts (PCTs). However, there has been no examination of whether disadvantage is associated with short stay unplanned admissions at PCT-level. The aim of this study was to determine whether differences between emergency hospital admission rates for breathing difficulty, feverish illness and diarrhoea are associated with population-level measures of multiple deprivation and child well-being, and whether there is variation by length of stay and age. Methods Analysis of hospital episode statistics and secondary analysis of Index of Multiple Deprivation (IMD) 2007 and Local Index of Child Well-being (CWI) 2009 in ten adjacent PCTs in North West England. The outcome measure for each PCT was the emergency admission rate to hospital for breathing difficulty, feverish illness and diarrhoea. Results 23,496 children aged 0-14 were discharged following emergency admission for breathing difficulty, feverish illness and/or diarrhoea during 2006/07. The emergency admission rate ranged from 27.9 to 62.7 per thousand. There were no statistically significant relationships between shorter (0 to 3 day) hospitalisations and the IMD or domains of the CWI. The rate for hospitalisations of 4 or more days was associated with the IMD (Kendall's taub = 0.64) and domains of the CWI: Environment (taub = 0.60); Crime (taub = 0.56); Material (taub = 0.51); Education (taub = 0.51); and Children in Need (taub = 0.51). This pattern was also evident in children aged under 1 year, who had the highest emergency admission rates. There were wide variations between the proportions of children discharged on the day of admission at different hospitals. Conclusions Differences between rates of the more common shorter (0 to 3 day) hospitalisations were not explained by deprivation or well-being measured at PCT-level. Indices of multiple deprivation and child well-being were only associated with rates of children's emergency admission for breathing difficulty, feverish illness and diarrhoea for hospitalisations of 4 or more days

CD90 is not constitutively expressed in functional innate lymphoid cells

Huge progress has been made in understanding the biology of innate lymphoid cells (ILC) by adopting several well-known concepts in T cell biology. As such, flow cytometry gating strategies and markers, such as CD90, have been applied to indentify ILC. Here, we report that most non-NK intestinal ILC have a high expression of CD90 as expected, but surprisingly a sub-population of cells exhibit low or even no expression of this marker. CD90-negative and CD90-low CD127+ ILC were present amongst all ILC subsets in the gut. The frequency of CD90-negative and CD90-low CD127+ ILC was dependent on stimulatory cues in vitro and enhanced by dysbiosis in vivo. CD90-negative and CD90-low CD127+ ILC were a potential source of IL-13, IFNγ and IL-17A at steady state and upon dysbiosis- and dextran sulphate sodium-elicited colitis. Hence, this study reveals that, contrary to expectations, CD90 is not constitutively expressed by functional ILC in the gut

Development of Autonomous Aerobraking (Phase 1)

The NASA Engineering and Safety Center received a request from Mr. Daniel Murri (NASA Technical Fellow for Flight Mechanics) to develop an autonomous aerobraking capability. An initial evaluation for all phases of this assessment was approved to proceed at the NESC Review Board meeting. The purpose of phase 1 of this study was to provide an assessment of the feasibility of autonomous aerobraking. During this phase, atmospheric, aerodynamic, and thermal models for a representative spacecraft were developed for both the onboard algorithm known as Autonomous Aerobraking Development Software, and a ground-based "truth" simulation developed for testing purposes. The results of the phase 1 assessment are included in this report

Integrating community children’s nursing in urgent and emergency care: a qualitative comparison of two teams in North West England

Background: Despite the policy principle that "children are best cared for at home whenever possible" children continue to have high rates of emergency department (ED) attendance and emergency hospital admission. Community Children's Nursing Teams (CCNTs) can care for acutely ill children at home but their potential to provide an alternative to ED attendance and hospitalisation depends on effective integration with other services in the urgent care system, such as EDs and Observation and Assessment Units (OAUs). Although challenges of integrating CCNTs have been identified, there has been no comparative assessment of the factors that facilitate or hinder integration of care of acutely ill children by CCNTs with the urgent care system. The aim of this study was to identify enablers and barriers to integration of CCNTs with urgent and emergency care. Methods: Comparative case studies were conducted of two CCNTs serving Primary Care Trusts in North West England. Twenty-two health professionals including CCNT managers and staff; paediatricians; nurses; children's ward, ED and OAU staff; commissioners of children's services; GPs and primary care staff were interviewed between June 2009 and February 2010. Qualitative data were analysed thematically using the Framework approach. Results: Barriers to integration included paediatricians' perceived lack of ownership of the CCNT, poor communication between consultants and community children's nurses (CCNs), and weak personal relationships. This prevented early referral to the CCNT as an alternative to hospital care. Enablers of integration included co-location and rotation of CCNs through urgent care settings including OAUs and EDs. This enabled nurses to develop skills, make decisions about referral to home care and gain the confidence of referring clinicians. Conclusions: Integration of CCNTs at multiple points in the urgent care system is required in order to provide an alternative to inappropriate ED attendances and emergency admission. The principal enablers and barriers are both aspects of normative integration, which involves shared understanding of the contribution of CCNTs and trusting relationships between practitioners. Co-location and rotation of CCNs through acute services can promote integration and appropriate referrals to CCNTs to support families to care for children at home