Defining and investigating difficult asthma: Developing quality indicators

SummaryBackgroundThere is no agreed definition of ‘difficult asthma’ or what investigations should be available to investigate these patients. Patients with difficult asthma remain symptomatic on high levels of treatment and are high users of medical resources.AimTo develop a set of quality indicators for the definition and investigation of difficult asthma.MethodModified RAND Appropriateness Method was used. An expert panel composed of nine hospital asthma specialists who run ‘difficult’ asthma clinics and were identified from a shortlist of key workers in the field. Indicators were rated as necessary to define and investigate difficult asthma.ResultsDifficult asthma was defined as ‘symptoms persisting beyond therapy consistent with step 4 of the British Thoracic Society (BTS) guidelines’ (high dose inhaled corticosteroids and long acting β2-agonists). Eighty-three indicators were identified (40 relating to definition and 43 relating to investigations). Of these 32 (39%) were rated as necessary: 7 out of 40 (18%) for defining difficult asthma and 23 out of 43 (53%) for investigations. Indicators of high medical resource usage were characteristic of the ‘difficult’ nature of the management of patient with difficult asthma. A framework for the investigation of these patients was created.ConclusionThe listed performance indicators identify a range of requirements that are necessary to define difficult asthma. Targeting of real needs in this group of patients will lead to better patient care and reduction of ‘waste’ in provision of healthcare

Three-Dimensional Engineered Bone from Bone Marrow Stromal Cells and Their Autogenous Extracellular Matrix

Most bone tissue engineering research uses porous three-dimensional (3D) scaffolds for cell seeding. In this work, scaffold-less 3D bone-like tissues were engineered from rat bone marrow stromal cells (BMSCs) and their autogenous extracellular matrix (ECM). The BMSCs were cultured on a 2D substrate in medium that induced osteogenic differentiation. After reaching confluence and producing a sufficient amount of their own ECM, the cells contracted their tissue monolayer around two constraint points, forming scaffold-less cylindrical engineered bone-like constructs (EBCs). The EBCs exhibited alizarin red staining for mineralization and alkaline phosphatase activity and contained type I collagen. The EBCs developed a periosteum characterized by fibroblasts and unmineralized collagen on the periphery of the construct. Tensile tests revealed that the EBCs in culture had a tangent modulus of 7.5+/-0.5MPa at 7 days post-3D construct formation and 29+/-9MPa at 6 weeks after construct formation. Implantation of the EBCs into rats 7 days after construct formation resulted in further bone development and vascularization. Tissue explants collected at 4 weeks contained all three cell types found in native bone: osteoblasts, osteocytes, and osteoclasts. The resulting engineered tissues are the first 3D bone tissues developed without the use of exogenous scaffolding.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78137/1/ten.tea.2007.0140.pd

Materials accounting and international safeguards for MOX facilities

Our experience with mixed oxide (MOX) fuel fabrication facilities leads us to conclude that there is inadequate guidance available to plant and process designers to make materials accounting systems timely, efficient, and minimally intrusive. A well designed state system for accounting and control of nuclear materials would be beneficial to plant operations and verification by the International Atomic Energy Agency (IAEA) or state regulatory agencies. Among the difficult accounting problems that arise in a large-scale MOX facility are the following: (1) process steps (such as the blending and splitting of powders) that require the accounting system to track material flow, calculate quantities based on previous measurements, and propagate uncertainties as part of data analysis; (2) extensive buffer storage areas involving long residence times that necessitate frequent corrections for material loss from radioactive decay; and (3) facility accounting at one level (for example, fuel pins) that must be reconciled with verification measurements at another level (for example, pin trays or assemblies). Approaches to addressing these problems include designing a special facility, simulating material flow, developing software for near-real-time materials accounting, and establishing achievable verification goals. This paper elaborates on these problems and proposes approaches to a materials accounting system design that considers facility, state, and IAEA safeguards and verification objectives. 11 refs., 1 fig., 1 tab

Unbounded violation of tripartite Bell inequalities

We prove that there are tripartite quantum states (constructed from random unitaries) that can lead to arbitrarily large violations of Bell inequalities for dichotomic observables. As a consequence these states can withstand an arbitrary amount of white noise before they admit a description within a local hidden variable model. This is in sharp contrast with the bipartite case, where all violations are bounded by Grothendieck's constant. We will discuss the possibility of determining the Hilbert space dimension from the obtained violation and comment on implications for communication complexity theory. Moreover, we show that the violation obtained from generalized GHZ states is always bounded so that, in contrast to many other contexts, GHZ states do in this case not lead to extremal quantum correlations. The results are based on tools from the theories of operator spaces and tensor norms which we exploit to prove the existence of bounded but not completely bounded trilinear forms from commutative C*-algebras.Comment: Substantial changes in the presentation to make the paper more accessible for a non-specialized reade

Origin of high density seabed pockmark fields and their use in inferring bottom currents

Some of the highest density pockmark fields in the world have been observed on the northwest Australian continental shelf (>700/km2) where they occur in muddy, organic-rich sediment around carbonate banks and paleochannels. Here we developed a semi-automated method to map and quantify the form and density of these pockmark fields (~220,000 pockmarks) and characterise their geochemical, sedimentological and biological properties to provide insight into their formative processes. These data indicate that pockmarks formed due to the release of gas derived from the breakdown of near-surface organic material, with gas accumulation aided by the sealing properties of the sediments. Sources of organic matter include adjacent carbonate banks and buried paleochannels. Polychaetes biodiversity appears to be affected negatively by the conditions surrounding dense pockmark fields since higher biodiversity is associated with low density fields. While regional bi-directionality of pockmark scours corresponds to modelled tidal flow, localised scattering around banks suggests turbulence. This multi-scale information therefore suggests that pockmark scours can act as proxy for bottom currents, which could help to inform modelling of benthic biodiversity pattern

A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency.

PURPOSE: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles. METHODS: We performed a prospective observational 12-month multicenter study in France via the CEREDIH network of regional PID reference centers from November 2010 to October 2011. All patients with PIDs requiring emergency hospital admission were included. RESULTS: A total of 200 admissions concerned 137 patients (73 adults and 64 children, 53% of whom had antibody deficiencies). Thirty admissions were reported for 16 hematopoietic stem cell transplantation recipients. When considering the 170 admissions of non-transplant patients, 149 (85%) were related to acute infections (respiratory tract infections and gastrointestinal tract infections in 72 (36%) and 34 (17%) of cases, respectively). Seventy-seven percent of the admissions occurred during winter or spring (December to May). The in-hospital mortality rate was 8.8% (12 patients); death was related to a severe infection in 11 cases (8%) and Epstein-Barr virus-induced lymphoma in 1 case. Patients with a central venous catheter (n = 19, 13.9%) were significantly more hospitalized for an infection (94.7%) than for a non-infectious reason (5.3%) (p = 0.04). CONCLUSION: Our data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode

Focal-plane detector system for the KATRIN experiment

The focal-plane detector system for the KArlsruhe TRItium Neutrino (KATRIN) experiment consists of a multi-pixel silicon p-i-n-diode array, custom readout electronics, two superconducting solenoid magnets, an ultra high-vacuum system, a high-vacuum system, calibration and monitoring devices, a scintillating veto, and a custom data-acquisition system. It is designed to detect the low-energy electrons selected by the KATRIN main spectrometer. We describe the system and summarize its performance after its final installation.Comment: 28 pages. Two figures revised for clarity. Final version published in Nucl. Inst. Meth.

Influence des cervidés sur la flore

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Evolution de la croissance radiale du hêtre (Fagus silvatica L) dans les Vosges. Premiers résultats sur le versant lorrain

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