The value of implementation and the value of information: combined and uneven development

<i>Aim</i>: In a budget-constrained health care system, the decision to invest in strategies to improve the implementation of cost-effective technologies must be made alongside decisions regarding investment in the technologies themselves and investment in further research. This article presents a single, unified framework that simultaneously addresses the problem of allocating funds between these separate but linked activities. <i>Methods</i>: The framework presents a simple 4-state world where both information and implementation can be either at the current level or "perfect". Through this framework, it is possible to determine the maximum return to further research and an upper bound on the value of adopting implementation strategies. The framework is illustrated through case studies of health care technologies selected from those previously considered by the UK National Institute for Health and Clinical Excellence (NICE). <i>Results</i>: Through the case studies, several key factors that influence the expected values of perfect information and perfect implementation are identified. These factors include the maximum acceptable cost-effectiveness ratio, the level of uncertainty surrounding the adoption decision, the expected net benefits associated with the technologies, the current level of implementation, and the size of the eligible population. <i>Conclusions</i>: Previous methods for valuing implementation strategies have not distinguished the value of efficacy research and the value of strategies to change the level of implementation. This framework demonstrates that the value of information and the value of implementation can be examined separately but simultaneously in a single framework. This can usefully inform policy decisions about investment in health care services, further research, and adopting implementation strategies that are likely to differ between technologies

Direct imaging of short-range order and its impact on deformation in Ti-6Al.

Chemical short-range order (SRO) within a nominally single-phase solid solution is known to affect the mechanical properties of alloys. While SRO has been indirectly related to deformation, direct observation of the SRO domain structure, and its effects on deformation mechanisms at the nanoscale, has remained elusive. Here, we report the direct observation of SRO in relation to deformation using energy-filtered imaging in a transmission electron microscope (TEM). The diffraction contrast is enhanced by reducing the inelastically scattered electrons, revealing subnanometer SRO-enhanced domains. The destruction of these domains by dislocation planar slip is observed after ex situ and in situ TEM mechanical testing. These results confirm the impact of SRO in Ti-Al alloys on the scale of angstroms. The direct confirmation of SRO in relationship to dislocation plasticity in metals can provide insight into how the mechanical behavior of concentrated solid solutions by the material's thermal history

Inequivalent contact structures on Boothby-Wang 5-manifolds

We consider contact structures on simply-connected 5-manifolds which arise as circle bundles over simply-connected symplectic 4-manifolds and show that invariants from contact homology are related to the divisibility of the canonical class of the symplectic structure. As an application we find new examples of inequivalent contact structures in the same equivalence class of almost contact structures with non-zero first Chern class.Comment: 27 pages; to appear in Math. Zeitschrif

A pilot study of change in fracture risk in patients with acute respiratory distress syndrome

INTRODUCTION: Acute skeletal muscle wasting is a major contributor to post critical illness physical impairment. However, the bone response remains uncharacterized. We prospectively investigated the early changes in bone mineral density (BMD) and fracture risk in critical illness. METHODS: Patients were prospectively recruited ≤ 24 hours following intensive care unit (ICU) admission to a University Teaching and a Community Hospital (August 2009 to April 2011).All were aged >18 years and expected to be intubated for >48 hours, spend >7 days in critical care and survive ICU admission. Forty-six patients were studied (55.3% male) with an age of 54.4 years (95% Confidence Interval (CI) 49.1-59.6)years and APACHE II score 23.9 (95%CI 22.4-25.5).Calcaneal Dual X-ray Absorptiometry (DXA) assessment of BMD was performed on day 1 and 10. Increase in fracture risk was calculated from the change in T-score. RESULTS: BMD did not change between day 1 and 10 in the cohort overall (0.434 (95%CI 0.405-0.463) vs. 0.425 g/cm(2) (95%CI 0.399-0.450), p = 0.58).Multivariable logistical regression revealed admission corrected calcium (OR 1.980 (95%CI 1.089-3.609), p = 0.026) and admission PaO2 to FiO2 ratio (OR 0.916 (95%CI 0.833-0.998), p = 0.044)to be associated with >2% loss of BMD. Patients with Acute Respiratory Distress Syndrome had a greater loss in BMD than those without (-2.81 (95%CI -5.73-0.118)%, n = 34 vs. 2.40 (95%CI 0.204-4.586)%,n = 12, p = 0.029). In the 34 patients with Acute Respiratory Distress Syndrome, fracture risk increased by 19.4% (95%CI 13.9-25.0%). CONCLUSIONS: Patients with acute respiratory distress syndrome demonstrated early and rapid bone demineralisation with associated increase in fracture risk

Alterations in vascular function in primary aldosteronism - a cardiovascular magnetic resonance imaging study

Introduction: Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV).<p></p> Methods: We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass.<p></p> Results: Subjects with PA had significantly lower aortic distensibilty and higher PWV compared to EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including aging. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular aging. As expected, aortic distensibility and PWV were closely correlated.<p></p> Conclusion: These results demonstrate that PA patients display increased arterial stiffness compared to EH, independent of vascular aging. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study.<p></p&gt

Sensorless speed control of five-phase PMSM drives with low current distortion

This paper introduces a design for a sensorless control of a five-phase PMSM drive working at low and zero speeds with low current distortion. The rotor position is obtained through tracking the saturation saliency by measuring the dynamic currents responses of the motor due to the IGBTs switching actions. It uses the fundamental PWM waveform obtained using the multi-phase space vector pulse width modulation only. The saliency tracking algorithm used in this paper doesn’t only improve the quality of the estimated position signals but also guarantees a minimum current distortion through reducing the modifications introduced on the PWM waveform. Simulation results are provided to verify the effectiveness of the proposed strategy for saliency tracking and current distortion minimizing of a five-phase PMSM motor drive over a wide speed ranges under different load conditions

EPR spectroscopy and molecular dynamics modelling: a combined approach to study liquid crystals

This review outlines the recent theoretical and computational developments for the prediction of motional electron paramagnetic resonance spectra with introduced spin probes from molecular dynamics simulations. The methodology is illustrated with applications to thermotropic and lyotropic liquid crystals at different phases and aggregate states

The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog

Chronic spinal cord dysfunction occurs in dogs as a consequence of diverse aetiologies, including long-standing spinal cord compression and insidious neurodegenerative conditions. One such neurodegenerative condition is canine degenerative myelopathy (DM), which clinically is a challenge to differentiate from other chronic spinal cord conditions. Although the clinical diagnosis of DM can be strengthened by the identification of the Sod1 mutations that are observed in affected dogs, genetic analysis alone is insufficient to provide a definitive diagnosis. There is a requirement to identify biomarkers that can differentiate conditions with a similar clinical presentation, thus facilitating patient diagnostic and management strategies. A comparison of the cerebrospinal fluid (CSF) protein gel electrophoresis profile between idiopathic epilepsy (IE) and DM identified a protein band that was more prominent in DM. This band was subsequently found to contain a multifunctional protein clusterin (apolipoprotein J) that is protective against endoplasmic reticulum (ER) stress-mediated apoptosis, oxidative stress, and also serves as an extracellular chaperone influencing protein aggregation. Western blot analysis of CSF clusterin confirmed elevated levels in DM compared to IE (p < 0.05). Analysis of spinal cord tissue from DM and control material found that clusterin expression was evident in neurons and that the clusterin mRNA levels from tissue extracts were elevated in DM compared to the control. The plasma clusterin levels was comparable between these groups. However, a comparison of clusterin CSF levels in a number of neurological conditions found that clusterin was elevated in both DM and chronic intervertebral disc disease (cIVDD) but not in meningoencephalitis and IE. These findings indicate that clusterin may potentially serve as a marker for chronic spinal cord disease in the dog; however, additional markers are required to differentiate DM from a concurrent condition such as cIVDD

The impact of predation by marine mammals on Patagonian toothfish longline fisheries

Predatory interaction of marine mammals with longline fisheries is observed globally, leading to partial or complete loss of the catch and in some parts of the world to considerable financial loss. Depredation can also create additional unrecorded fishing mortality of a stock and has the potential to introduce bias to stock assessments. Here we aim to characterise depredation in the Patagonian toothfish (Dissostichus eleginoides) fishery around South Georgia focusing on the spatio-temporal component of these interactions. Antarctic fur seals (Arctocephalus gazella), sperm whales (Physeter macrocephalus), and orcas (Orcinus orca) frequently feed on fish hooked on longlines around South Georgia. A third of longlines encounter sperm whales, but loss of catch due to sperm whales is insignificant when compared to that due to orcas, which interact with only 5% of longlines but can take more than half of the catch in some cases. Orca depredation around South Georgia is spatially limited and focused in areas of putative migration routes, and the impact is compounded as a result of the fishery also concentrating in those areas at those times. Understanding the seasonal behaviour of orcas and the spatial and temporal distribution of “depredation hot spots” can reduce marine mammal interactions, will improve assessment and management of the stock and contribute to increased operational efficiency of the fishery. Such information is valuable in the effort to resolve the human-mammal conflict for resources

TAM receptor tyrosine kinase function and the immunopathology of liver disease.

Tyro3, Axl, MERTK (TAM) receptor tyrosine kinases are implicated in the regulation of the innate immune response through clearance of apoptotic cellular debris and control of cytokine signaling cascades. As a result they are pivotal in regulating the inflammatory response to tissue injury. Within the liver, immune regulatory signaling is employed to prevent the overactivation of innate immunity in response to continual antigenic challenge from the gastrointestinal tract. In this review we appraise current understanding of the role of TAM receptor function in the regulation of both innate and adaptive immunity, with a focus on its impact upon hepatic inflammatory pathology