General practitioners' reasons for removing patients from their lists: postal survey in England and Wales

The removal of patients from doctors' lists causes con­ siderable public and political concern, with speculation that patients are removed for inappropriate, including financial, reasons. In 1999 the House of Commons Select Committee on Public Administration noted that little evidence was available on either the frequency of, or the reasons for, removal of patients. National statistics do not distinguish between patients removed after moving out of a practice area and those removed for other reasons. Two postal surveys have reported why general practitioners might, in general, remove patients, and one small study has described the reasons doctors give for particular removals. We therefore determined the current scale of, and doctors' reasons for, removal of patients from their lists in Eng­ land and Wales

Characterisation of the cold metal transfer (CMT) process and its application for low dilution cladding

The process characteristics of the synergic cold metal transfer (CMT) process have been examined for welding aluminium alloy. Utilising a simple backlighting system and through the arc monitoring the droplet transfer modes were identified. Whilst the modified short circuit mode was evident for the lower parameter range, a two part transfer mode based upon a combination of spray and short circuit transfer was observed for the mid to upper parameter range. The technology was also explored as a cladding process for applying to ternary alloyed (Al–Cu–Mg) aluminium plate. This alloy system is known to be susceptible to solidification cracking when MIG welded using the binary Al-2319 (Al–Cu) filler wire, this being due to the wide element freezing range of the weld resulting from mixing with the base material. Utilising this filler, weld dilution ratios for both CMT and pulsed welding were identified across the examined parameter range. The CMT process exhibited greater control of dilution that enabled deposition of a quasi-binary (Al–Cu) layer exhibiting a less crack susceptible composition. Onto this layer conventional MIG welding could be applied which could potentially eradicate cracking using a binary fi

Arc welding of high strength aluminium alloys for armour systems applications

The ternary Al-Cu-Mg system 2xxx series aluminium alloys were examined as construction materials for armour system applications based upon comparable ballistic properties to the currently employed Al-7xxx series alloys. Utilising MIG welding solidification cracking was evident when welding constrained Al-2024 candidate base material using Al-2319 filler, the only available consumable wire for this series. A previously developed thermodynamic model suggested that an incompatible weld chemistry resulted when welding with this filler which would result in hot cracking due to a wide weld pool freezing range and a low volume fraction of eutectic liquid. As this filler wire was the only commercially available Al-2xxx filler this was seen as the principal limiting factor for exploiting this alloy series. The solution was to vary and control weld chemistry. Two approaches were taken. Firstly advanced arc welding was used to control weld dilution with the base material. A clad layer exhibiting a less crack susceptible composition was deposited using the Cold Metal Transfer process and the binary Al-2319 filler wire. Onto this layer the same filler could then be deposited to provide a structural joint. Although not fully validated, by limiting weld dilution with the base material this technique showed potential as an alternative method for suppressing solidification cracking. The second approach, which forms the core of this work, adapted the conventional tandem MIG welding process to mix different series consumable fillers in a single weld pool to control weld composition. A range of ternary weld mixtures were produced which resulted in the development of a robust thermodynamic model. Validation using this system resulted in weld cracking being eradicated. The concept was then further developed to weld using three filler wires; this expanded the mixing range and allowed further model validation. A range of crack free compositions were produced with differing mechanical properties. An optimum weld composition was determined that was then used for characterisation of the weldment. By varying heat input, base material HAZ softening was controlled with joint failure confined to the weld / base material interface. This was attributed to grain boundary liquation due to the welding temperatures involved resulting in solute rich grain boundaries. These areas did not deform easily under tensile loading initiating fracture of the joint. Acceptable joint strengths were realised however ductility was reduced due to the identified failure mode. Although not tested to military specifications, acceptable mechanical test values were recorded which were closely compliant with the minimum requirements for armour system specifications. As a consequence a filler wire composition was recommended for future prototype development

Open Source Verification under a Cloud

An experiment in providing volunteer cloud computing support for automated audits of open source code is described here, along with the supporting theory. Certification and the distributed and piecewise nature of the underlying verification computation are among the areas formalised in the theory part. The eventual aim of this research is to provide a means for open source developers who seek formally backed certification for their project to run fully automated analyses on their own source code. In order to ensure that the results are not tampered with, the computation is anonymized and shared with an ad-hoc network of volunteer CPUs for incremental completion. Each individual computation is repeated many times at different sites, and sufficient accounting data is generated to allow each computation to be refuted

CMT Welding of Titanium and Stainless Steel Using CuSi3 Electrode

The article deals with the possibility of a tight permanent joint of X5CrNi 18-10 austenitic steel and UNS N50400 titanium. The nuclear and chemical industries are in particular interested in solving this problem. The joining by means of fusion welding has come up against unreliability due to the formation of brittle intermetallic compounds between titanium and iron. The article deals with joining of these two heterogeneous materials by an innovative CMT welding method. CuSi3 soldering electrode was chosen as the additional material. Protective atmosphere consisting of clean argon has been chosen due to the undesirable gas absorption by titanium at temperatures over 600 oC. The results will compare different welding parameters and their impact on the quality of the weld joint. The quality of the created welds will be verified on the basis of the tensile test and the results will be graphically visualized. The microhardness in the weld and its surroundings will be measured. The microhardness measurement results will be graphically displayed. The experimental results will be supplemented by macrostructure snapshots and metallographic analysis snapshots.O

Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain interface.

Members of the epidermal growth factor receptor family (EGFR/ERBB1, ERBB2/HER2, ERBB3/HER3 and ERBB4/HER4) are key targets for inhibition in cancer therapy. Critical for activation is the formation of an asymmetric dimer by the intracellular kinase domains, in which the carboxy-terminal lobe (C lobe) of one kinase domain induces an active conformation in the other. The cytoplasmic protein MIG6 (mitogen-induced gene 6; also known as ERRFI1) interacts with and inhibits the kinase domains of EGFR and ERBB2 (refs 3-5). Crystal structures of complexes between the EGFR kinase domain and a fragment of MIG6 show that a approximately 25-residue epitope (segment 1) from MIG6 binds to the distal surface of the C lobe of the kinase domain. Biochemical and cell-based analyses confirm that this interaction contributes to EGFR inhibition by blocking the formation of the activating dimer interface. A longer MIG6 peptide that is extended C terminal to segment 1 has increased potency as an inhibitor of the activated EGFR kinase domain, while retaining a critical dependence on segment 1. We show that signalling by EGFR molecules that contain constitutively active kinase domains still requires formation of the asymmetric dimer, underscoring the importance of dimer interface blockage in MIG6-mediated inhibition

Mechanistic insights into the effect of RUNX1/ETO knockdown in t(8;21) AML

The mutation of transcription factor genes is a main cause for acute myeloid leukaemia. RUNX1/ETO, the product of the t(8;21) chromosomal translocation, subverts normal blood cell development by impairing myeloid differentiation. RUNX1/ETO knockdown alleviates this block, with a global reprogramming of transcription factor binding and initiation of myeloid differentiation. Co-depletion of the myeloid transcription factor C/EBPα with RUNX1/ETO suppressed this differentiation response. Furthermore, C/EBPα overexpression largely phenocopied the effect of RUNX1/ETO knockdown. Our data show that low levels of C/EBPα are critical to the maintenance of t(8;21) AML and that C/EBPα drives the response to RUNX1/ETO depletion. To examine how changes in transcription factor binding impact on the activity of cisregulatory elements we mapped genome wide promoter-distal-element interactions in a t(8;21) AML cell line, via Capture HiC, and found that hundreds of interactions were altered by RUNX1/ETO knockdown. Differentially interacting elements exhibited changes in C/EBPα binding and were enriched for the CTCF motif. Our results demonstrate that the presence or absence of RUNX1/ETO has a profound impact on the intra-nuclear organisation of t(8;21) AML cells, and indicate which transcription factors are driving these changes. This work provides a novel mechanism for the RUNX1/ETO mediated differentiation block in t(8;21) AML

Cholesterol and coronary heart disease: screening and treatment

Coronary heart disease (CHD) is a major cause of morbidity and mortality in the United Kingdom, accounting for just under one quarter of all deaths in 1995: 27% among men and 21% among women.1 Although many CHD deaths occur among elderly people, CHD accounts for 31% of male and 13% of female deaths within the 45–64 age group