Discovery of New Molecular Subtypes in Oesophageal Adenocarcinoma

A large number of patients suffering from oesophageal adenocarcinomas do not respond to conventional chemotherapy; therefore, it is necessary to identify new predictive biomarkers and patient signatures to improve patient outcomes and therapy selections. We analysed 87 formalin-fixed and paraffin-embedded (FFPE) oesophageal adenocarcinoma tissue samples with a reverse phase protein array (RPPA) to examine the expression of 17 cancer-related signalling molecules. Protein expression levels were analysed by unsupervised hierarchical clustering and correlated with clinicopathological parameters and overall patient survival. Proteomic analyses revealed a new, very promising molecular subtype of oesophageal adenocarcinoma patients characterised by low levels of the HSP27 family proteins and high expression of those of the HER family with positive lymph nodes, distant metastases and short overall survival. After confirmation in other independent studies, our results could be the foundation for the development of a Her2-targeted treatment option for this new patient subgroup of oesophageal adenocarcinoma

The contrasting role of technology as both supportive and hindering in the everyday lives of people with mild cognitive deficits: a focus group study

Background: It is well known that people with mild cognitive deficits face challenges when performing complex everyday activities, and that the use of technology has become increasingly interwoven with everyday activities. However, less is known of how technology might be involved, either as a support or hindrance, in different areas of everyday life and of the environments where challenges appear. The aim of this study was to investigate the areas of concern where persons with cognitive deficits meet challenges in everyday life, in what environments these challenges appear and how technology might be involved as part of the challenge and/or the solution to the challenge. Methods: Data were gathered through four focus group interviews with participants that live with cognitive deficits or cohabit with a person with cognitive deficits, plus health professionals and researchers in the field. Data were transcribed, coded and categorized, and finally synthesized to trace out the involvement of technology. Results: Five areas of concern in everyday life were identified as offering challenges to persons with cognitive deficits: A) Managing personal finances, B) Getting around, C) Meeting family and friends, D) Engaging with culture and media and, E) Doing everyday chores. Findings showed that the involvement of technology in everyday activities was often contrastive. It could be hindering and evoke stress, or it could bring about feelings of control; that is, being a part of the solution. The involvement of technology was especially obvious in challenges linked to Managing personal finances, which is a crucial necessity in many everyday activities. In contrast, technology was least obviously involved in the area Socializing with family and friends. Conclusions: The findings imply that technology used for orientation and managing finances, often used outside home, would benefit from being further developed in order to be more supportive; i.e. accessible and usable. To make a positive change for many people, the ideas of inclusive design fit well for this purpose and would contribute to an age-friendly society

Slant Hole Completion Test, Cozzette and Paludal production testing

The Slant Hole Completion Test has been successful in providing good technology transfer to the oil and gas industry. The gas-producing rate from the Cozzette horizontal open-hole interval was significantly greater than from offset vertical wells. The source of water production from the Cozzette is not presently understood. Diagnosis of the water production mechanism is vital to economic exploitation of the Cozzette gas resource using horizontal well technology. Stimulation in a high-angle cased and cemented wellbore, such as the Paludal 2, 3 and 4 intervals in SHCT No. 1, is more difficult because of high near-wellbore stress that results in higher treating pressures. Low gas production potential following the Paludal 2, 3 and 4 stimulation may result from damage to the natural fracture system resulting from casing cementing operations. Comparison of gas production rates in SHCT No. 1 and MWX No. 1 following similar stimulations in the Paludal 3 and 4 intervals, indicate there is no advantage to a hydraulic fracture treatment in a slant wellbore when compared to a vertical wellbore

Quantitative and integrated proteome and microRNA analysis of endothelial replicative senescence.

Age-related changes in vascular functioning are a harbinger of cardiovascular disease but the biological mechanisms during the progression of endothelial senescence have not been studied. We investigated alterations in the proteome and miRNA profiles in the course of replicative senescence using primary human umbilical vein endothelial cells as an in vitro vascular model. Quantitative proteomic profiling from early growth stage to senescence was performed by isotope-coded protein label coupled to LC-ESI-MS/MS analysis. Some proteins consistently changed their expression during the senescence whereas others appeared as deregulated only during the late senescence. The latter was accompanied by alterations in morphology of senescent endothelial cells. MicroRNA expression profiling revealed transient changes in the level of miR-16-5p, miR-28-3p and miR-886-5p in the early senescence, decrease in the level of miR-106b-3p at the late stage, and continuous changes in the expression of miR-181a-5p and miR-376a-3p during the whole senescence process. Integrating data on proteomic and microRNA changes indicated potential crosstalk between specific proteins and non-coding RNAs in the regulation of metabolism, cell cycle progression and cytoskeletal organization in the endothelial senescence. The knowledge of molecular targets that change during the senescence can ultimately contribute to a better understanding and prevention of age-related vascular diseases. SIGNIFICANCE: Endothelial cell senescence has been associated to age-related cardiovascular disease. Although replicative senescence was discovered more than 50years ago, detailed molecular mechanisms behind this phenomenon remain to be elucidated. This study describes detailed proteome and miRNAome analyses in the progressing senescence of human umbilical vein endothelial cells. The in silico integration of the two data sets indicated the important role of miRNAs in the regulation of cell cycle progression, adhesion and metabolic alteration in the cellular aging. This study adds to our knowledge of age-induced vascular alterations and contributes to our understanding and prevention of age-related vascular diseases