Following the funding trail: Financing, nurses and teamwork in Australian general practice

Contains fulltext : 97927.pdf (publisher's version ) (Open Access)BACKGROUND: Across the globe the emphasis on roles and responsibilities of primary care teams is under scrutiny. This paper begins with a review of general practice financing in Australia, and how nurses are currently funded. We then examine the influence on funding structures on the role of the nurse. We set out three dilemmas for policy-makers in this area: lack of an evidence base for incentives, possible untoward impacts on interdisciplinary functioning, and the substitution/enhancement debate. METHODS: This three year, multimethod study undertook rapid appraisal of 25 general practices and year-long studies in seven practices where a change was introduced to the role of the nurse. Data collected included interviews with nurses (n = 36), doctors (n = 24), and managers (n = 22), structured observation of the practice nurse (51 hours of observation), and detailed case studies of the change process in the seven year-long studies. RESULTS: Despite specific fee-for-service funding being available, only 6% of nurse activities generated such a fee. Yet the influence of the funding was to focus nurse activity on areas that they perceived were peripheral to their roles within the practice. CONCLUSIONS: Interprofessional relationships and organisational climate in general practices are highly influential in terms of nursing role and the ability of practices to respond to and utilise funding mechanisms. These factors need to be considered, and the development of optimal teamwork supported in the design and implementation of further initiatives that financially support nursing in general practice

OGLE-2017-BLG-1186: first application of asteroseismology and Gaussian processes to microlensing

We present the analysis of the event OGLE-2017-BLG-1186 from the 2017 Spitzer microlensing campaign. This is a remarkable microlensing event because its source is photometrically bright and variable, which makes it possible to perform an asteroseismic analysis using ground-based data. We find that the source star is an oscillating red giant with average timescale of ∼9 days. The asteroseismic analysis also provides us source properties including the source angular size (∼27μas) and distance (∼11.5 kpc), which are essential for inferring the properties of the lens. When fitting the light curve, we test the feasibility of Gaussian Processes (GPs) in handling the correlated noise caused by the variable source. We find that the parameters from the GP model are generally more loosely constrained than those from the traditional χ2 minimization method. We note that this event is the first microlensing system for which asteroseismology and GPs have been used to account for the variable source. With both finite-source effect and microlens parallax measured, we find that the lens is likely a ∼0.045 M⊙ brown dwarf at distance ∼9.0 kpc, or a ∼0.073 M⊙ ultracool dwarf at distance ∼9.8 kpc. Combining the estimated lens properties with a Bayesian analysis using a Galactic model, we find a 35% probability for the lens to be a bulge object and 65% to be a background disk object

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Hippo signalling governs cytosolic nucleic acid sensing through YAP/TAZ-mediated TBK1 blockade

The Hippo pathway senses cellular conditions and regulates YAP/TAZ to control cellular and tissue homeostasis, while TBK1 is central for cytosolic nucleic acid sensing and antiviral defence. The correlation between cellular nutrient/physical status and host antiviral defence is interesting but not well understood. Here we find that YAP/TAZ act as natural inhibitors of TBK1 and are vital for antiviral physiology. Independent of transcriptional regulation and through the transactivation domain, YAP/TAZ associate directly with TBK1 and abolish virus-induced TBK1 activation, by preventing TBK1 Lys63-linked ubiquitylation and the binding of adaptors/substrates. Accordingly, YAP/TAZ deletion/depletion or cellular conditions inactivating YAP/TAZ through Lats1/2 kinases relieve TBK1 suppression and boost antiviral responses, whereas expression of the transcriptionally inactive YAP dampens cytosolic RNA/DNA sensing and weakens the antiviral defence in cells and zebrafish. Thus, we describe a function of YAP/TAZ and the Hippo pathway in innate immunity, by linking cellular nutrient/physical status to antiviral host defence

Varicella Viruses Inhibit Interferon-Stimulated JAK-STAT Signaling through Multiple Mechanisms

Varicella zoster virus (VZV) causes chickenpox in humans and, subsequently, establishes latency in the sensory ganglia from where it reactivates to cause herpes zoster. Infection of rhesus macaques with simian varicella virus (SVV) recapitulates VZV pathogenesis in humans thus representing a suitable animal model for VZV infection. While the type I interferon (IFN) response has been shown to affect VZV replication, the virus employs counter mechanisms to prevent the induction of anti-viral IFN stimulated genes (ISG). Here, we demonstrate that SVV inhibits type I IFN-activated signal transduction via the JAK-STAT pathway. SVV-infected rhesus fibroblasts were refractory to IFN stimulation displaying reduced protein levels of IRF9 and lacking STAT2 phosphorylation. Since previous work implicated involvement of the VZV immediate early gene product ORF63 in preventing ISG-induction we studied the role of SVV ORF63 in generating resistance to IFN treatment. Interestingly, SVV ORF63 did not affect STAT2 phosphorylation but caused IRF9 degradation in a proteasome-dependent manner, suggesting that SVV employs multiple mechanisms to counteract the effect of IFN. Control of SVV ORF63 protein levels via fusion to a dihydrofolate reductase (DHFR)-degradation domain additionally confirmed its requirement for viral replication. Our results also show a prominent reduction of IRF9 and inhibition of STAT2 phosphorylation in VZV-infected cells. In addition, cells expressing VZV ORF63 blocked IFN-stimulation and displayed reduced levels of the IRF9 protein. Taken together, our data suggest that varicella ORF63 prevents ISG-induction both directly via IRF9 degradation and indirectly via transcriptional control of viral proteins that interfere with STAT2 phosphorylation. SVV and VZV thus encode multiple viral gene products that tightly control IFN-induced anti-viral responses

Gene expression variability across cells and species shapes innate immunity.

As the first line of defence against pathogens, cells mount an innate immune response, which varies widely from cell to cell. The response must be potent but carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here we characterize the innate immune response's transcriptional divergence between species and variability in expression among cells. Using bulk and single-cell transcriptomics in fibroblasts and mononuclear phagocytes from different species, challenged with immune stimuli, we map the architecture of the innate immune response. Transcriptionally diverging genes, including those that encode cytokines and chemokines, vary across cells and have distinct promoter structures. Conversely, genes that are involved in the regulation of this response, such as those that encode transcription factors and kinases, are conserved between species and display low cell-to-cell variability in expression. We suggest that this expression pattern, which is observed across species and conditions, has evolved as a mechanism for fine-tuned regulation to achieve an effective but balanced response

Glucocorticosteroids enhance replication of respiratory viruses: effect of adjuvant interferon.

Glucocorticosteroids (GCS) are used on a daily basis to reduce airway inflammation in asthma and chronic obstructive pulmonary disease (COPD). This treatment is usually escalated during acute disease exacerbations, events often associated with virus infections. We examined the impact of GCS on anti-viral defences and virus replication and assessed supplementary interferon (IFN) treatment. Here, we report that treatment of primary human airway cells in vitro with GCS prior to rhinovirus (RV) or influenza A virus (IAV) infection significantly reduces the expression of innate anti-viral genes and increases viral replication. Mice given intranasal treatment with GCS prior to IAV infection developed more severe disease associated with amplified virus replication and elevated inflammation in the airways. Adjuvant IFN treatment markedly reduced GCS-amplified infections in human airway cells and in mouse lung. This study demonstrates that GCS cause an extrinsic compromise in anti-viral defences, enhancing respiratory virus infections and provides a rationale for adjuvant IFN treatment

Tables of gamma rays from (η,γ) produced nuclides.

Gamma ray energies from radioactive (η,γ) produced nuclides have been measured very accurately in the past few years and have been compiled in a publication by Lederer et al. (1967). However, these data are not presented in a manner which allows rapid identification of gamma spectra and although earlier publications such as Crouthamel (1960) and Heath (1964) have gamma ray data in a suitable form, the values of energies given are less precise that those in Lederer et al. The energies and abundances in the following tables are taken from Lederer et a. and rearranged in a form suitable for rapid identification of gamma spectra: Table 1 - Major gamma rays ordered by energy (each energy followed by all other gamma rays from that particular nuclide). Table 2 - All gamma rays ordered by energy Table 3 - Gamma rays from mass ordered nuclides. Similar tables containing data on fission products are being compiled. Half-lives start at two minutes, this time being chosen to suit irradiation and counting procedures in our laboratories. However, tables with half-lives from one second are available from the authors. Nuclides with characteristic x-rays and gamma rays less that 30 keV are not included in the tables. Only the immediate daughters of thorium and uranium are given in the Active Relation column. Other explanatory notes precede each table

Submarine pyroclastic deposits formed during the 20th May 2006 dome collapse of the Soufriere Hills Volcano, Montserrat

The 20th May 2006 lava dome collapse of the Soufrière Hills Volcano, Montserrat, had a total non-dense rock equivalent (non-DRE) collapse volume of approximately 115 × 106 m3. The majority of this volume was deposited into the ocean. The collapse was rapid, 85% of the mobilized volume being removed in just 35 min, giving peak pyroclastic flow flux of 66 × 103 m3 s−1. Channel and levee facies on the submarine flanks of the volcano and formation of a thick, steep-sided ridge, suggest that the largest and most dense blocks were transported proximally as a high concentration granular flow. Of the submerged volume, 30% was deposited from the base of this granular flow, forming a linear, high-relief ridge that extends 7 km from shore. The remaining 70% of the submerged volume comprises the finer grain sizes, which were transported at least 40 km by turbidity currents on gradients of <2°. At several localities, the May 2006 distal turbidity currents ran up 200 m of topography and eroded up to 20 cm of underlying substrate. Multiple turbidites are preserved, representing current reflection from the graben margins and deflection around topography. The high energy of the May 2006 collapse resulted in longer submarine run out than the larger (210 × 106 m3) Soufrière Hills dome collapse in July 2003