Does a Patient-Held Quality-of-Life Diary Benefit Patients With Inoperable Lung Cancer?

Purpose To examine the effect of weekly completion of a patient-held quality-of-life (QOL) diary in routine oncology practice for palliative care patients.

Germanium on Sapphire By Wafer Bonding

This paper describes the creation of a germanium on sapphire platform, via wafer bonding technology, for system-on-a-chip applications. Similar thermal coefficients of expansion between germanium (5.8 x 10-6 K-1) and sapphire (5 x 10-6 K-1) make the bonding of germanium to sapphire a reality. Germanium directly bonded to sapphire results in microvoid generation during post bond annealing. Inclusion of an interface layer such as silicon dioxide layer by plasma enhanced chemical vapour deposition, prior to bonding, results in a microvoid free bond interface after annealing. Grinding and polishing of the subsequent germanium layer has been achieved leaving a thick germanium on sapphire (GeOS) substrate. Submicron GeOS layers have also been achieved with hydrogen/helium co-implantation and layer transfer. Circular geometry transistors exhibiting a field effect mobility of 890 cm2/V s have been fabricated onto the thick germanium on sapphire layer.

Hoxa6 potentiates short-term hemopoietic cell proliferation and extended self-renewal.

Hemopoietic progenitor cells express clustered homeobox (Hox) genes in a pattern characteristic of their lineage and stage of differentiation. In general, HOX expression tends to be higher in more primitive and lower in lineage-committed cells. These trends have led to the hypothesis that self-renewal of hemopoietic stem/progenitor cells is HOX-dependent and that dysregulated HOX expression underlies maintenance of the leukemia-initiating cell. Gene expression profile studies support this hypothesis and specifically highlight the importance of the HOXA cluster in hemopoiesis and leukemogenesis. Within this cluster HOXA6 and HOXA9 are highly expressed in patients with acute myeloid leukemia and form part of the "Hox code" identified in murine models of this disease. We have examined endogenous expression of Hoxa6 and Hoxa9 in purified primary progenitors as well as four growth factor-dependent cell lines FDCP-Mix, EML, 32Dcl3, and Ba/F3, representative of early multipotential and later committed precursor cells respectively. Hoxa6 was consistently higher expressed than Hoxa9, preferentially expressed in primitive cells and was both growth-factor and cell-cycle regulated. Enforced overexpression of HOXA6 or HOXA9 in FDCP-Mix resulted in increased proliferation and colony formation but had negligible effect on differentiation. In both FDCP-Mix and the more committed Ba/F3 precursor cells overexpression of HOXA6 potentiated factor-independent proliferation. These findings demonstrate that Hoxa6 is directly involved in fundamental processes of hemopoietic progenitor cell development.

Solvent-free synthesis of metal complexes

Avoiding the use of solvents in synthesis can reduce environmental contamination and even be more convenient than using solvent-based synthesis. In this tutorial review we focus on recent research into the use of mechanochemistry ( grinding) to synthesise metal complexes in the absence of solvent. We include synthesis of mononuclear complexes, coordination clusters, spacious coordination cages, and 1-, 2- and 3-dimensional coordination polymers ( metal organic frameworks) which can even exhibit microporosity. Remarkably, in many cases, mechanochemical synthesis is actually faster and more convenient than the original solvent-based methods. Examples of solvent-free methods other than grinding are also briefly discussed, and the positive outlook for this growing topic is emphasised.

The Gerontological Imagination : Crime Policy and Older Prisoners

The Gerontological Imagination, Crime Policy and Older Prisoners This paper will discuss the needs of a group that more often than not has been ignored by criminologists and gerontologists: older offenders in prison. In relation to the disci-pline of criminology, I want to suggest that the gerontological and criminological ima-gination indeed are creative, resourceful, eclectic and can cross disciplinary boundaries. By drawing on the concept of the sociological imagination “which works between the personal troubles of milieu” and “the public issues of social structure” (Mills, 1959: 8): this paper will draw out the troubles and concerns of an aging prison population from a gerontological and criminological theoretical perspective. As the reader, you may be asking: why integrate the discipline of gerontology and criminology?

Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription

Background: Glycogen synthase kinase-3 (GSK-8) is a serine/threonine protein kinase, the activity of which is inhibited by a variety of extracellular stimuli including insulin, growth factors, cell specification factors and cell adhesion. Consequently, inhibition of GSK-3 activity has been proposed to play a role in the regulation of numerous signalling pathways that elicit pleiotropic cellular responses. This report describes the identification and characterisation of potent and selective small molecule inhibitors of GSK-3.

Identification of gene networks associated with acute myeloid leukemia by comparative molecular methylation and expression profiling

Around 80% of acute myeloid leukemia (AML) patients achieve a complete remission, however many will relapse and ultimately die of their disease. The association between karyotype and prognosis has been studied extensively and identified patient cohorts as having favourable [e.g. t(8; 21), inv (16)/t(16; 16), t(15; 17)], intermediate [e.g. cytogenetically normal (NK-AML)] or adverse risk [e.g. complex karyotypes]. Previous studies have shown that gene expression profiling signatures can classify the sub-types of AML, although few reports have shown a similar feature by using methylation markers. The global methylation patterns in 19 diagnostic AML samples were investigated using the Methylated CpG Island Amplification Microarray (MCAM) method and CpG island microarrays containing 12,000 CpG sites. The first analysis, comparing favourable and intermediate cytogenetic risk groups, revealed significantly differentially methylated CpG sites (594 CpG islands) between the two subgroups. Mutations in the NPM1 gene occur at a high frequency (40%) within the NK-AML subgroup and are associated with a more favourable prognosis in these patients. A second analysis comparing the NPM1 mutant and wild-type research study subjects again identified distinct methylation profiles between these two subgroups. Network and pathway analysis revealed possible molecular mechanisms associated with the different risk and/or mutation sub-groups. This may result in a better classification of the risk groups, improved monitoring targets, or the identification of novel molecular therapies.

Clinical Utility of Microarray-Based Gene Expression Profiling in the Diagnosis and Subclassification of Leukemia: Report From the International Microarray Innovations in Leukemia Study Group

The Microarray Innovations in Leukemia study assessed the clinical utility of gene expression profiling as a single test to subtype leukemias into conventional categories of myeloid and lymphoid malignancies. METHODS: The investigation was performed in 11 laboratories across three continents and included 3,334 patients. An exploratory retrospective stage I study was designed for biomarker discovery and generated whole-genome expression profiles from 2,143 patients with leukemias and myelodysplastic syndromes. The gene expression profiling-based diagnostic accuracy was further validated in a prospective second study stage of an independent cohort of 1,191 patients. RESULTS: On the basis of 2,096 samples, the stage I study achieved 92.2% classification accuracy for all 18 distinct classes investigated (median specificity of 99.7%). In a second cohort of 1,152 prospectively collected patients, a classification scheme reached 95.6% median sensitivity and 99.8% median specificity for 14 standard subtypes of acute leukemia (eight acute lymphoblastic leukemia and six acute myeloid leukemia classes, n = 693). In 29 (57%) of 51 discrepant cases, the microarray results had outperformed routine diagnostic methods. CONCLUSION: Gene expression profiling is a robust technology for the diagnosis of hematologic malignancies with high accuracy. It may complement current diagnostic algorithms and could offer a reliable platform for patients who lack access to today's state-of-the-art diagnostic work-up. Our comprehensive gene expression data set will be submitted to the public domain to foster research focusing on the molecular understanding of leukemias