Large scale projects : management, design and execution

This study deals with a topic which, probably more than any other, directly involves the continuing challenges of development and the improvement of the living environment in Developing Countries, but with particular reference to Saudi Arabia. It is through Project Management that Owners can direct and manage the myriad tasks and activities which are needed to accomplish the design and construction of diverse facilities. Virtually anyone with a modest knowledge of what is involved in the management of a large construction project knows that it is no simple task. The study does not attempt to develop an inflexible methodology, but, rather a concept which could be revised and perfected. The author's own experience in recent years has confirmed the validity and usefulness of a particular approach to project management. This study is an attest to provide a system which differs from all other known systems and which will serve the needs of the building owner to give him a greater degree of control in the construction process. It acknowledges that owners cannot possibly provide all the necessary technical expertise, so the system should be simple, covering important issues, and ignoring tasks which are the responsibility of specialist consultants. It is written primarily for personnel involved in policy making and decision taking. Thus the contents are aimed at construction executives, architects, engineers, financiers and others involved in the planning, design, construction, operation and financing of a large scale project. ii The study attempts to arrive at a system which encourages an atmosphere of creative thinking and an acceptance of change. It is, therefore, an organised, systematic approach recognising and containing the elements of planning, scheduling and estimating as well as consultant and contractor selection, tendering, reporting, control and analysis of the important variables of time, money and quality

Mechanism of pentoxifylline mediated down-regulation of killer lineage cell functions

The authors reported recently that endotoxaemia mediated elevated levels of tumour necrosis factor (TNF-α) and interleukin-1α (IL-1α) were involved in the pathophysiology of acute heat stroke patients. Pentoxifylline (PTX) is known to modulate neutrophil functions. In the present study the effects of PTX on lipopolysaccharide (LPS) and cytokine induced T-cell and macrophage (ΦM) activation, and on natural killer (NK) cell and lymphokine activated killer (LAK) cell mediated cytotoxicity were examined. Finally, the effect of PTX on the expression of adhesion molecules (LFA-1, Mac-1 and ICAM-1), and cytokine (IL-1α, IL-2, TNF-α, IL-6 and IFN-γ) production and their surface receptor expression in response to LPS activation was investigated. PTX free cultures served as a control. Results revealed that PTX can down-regulate all the above-mentioned immunological parameters in a dosedependent manner. These findings might have far reaching clinical implications

Tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA is elevated in advanced stages of thyroid carcinoma

Tumour cell invasion and metastasis is a multistep process that involves the degradation of extracellular matrix proteins by matrix metalloproteinases (MMPs). Tissue inhibitors of metalloproteinases (TIMPs) act as negative regulators of MMPs and thus prevent tumour cell invasion and metastasis by preserving extracellular matrix (ECM) integrity. In the present study we examined the expression of one member of TIMPs, TIMP-1, in 39 thyroid tumour specimens and two thyroid carcinoma cell lines (NPA and SW579). We also investigated the effect of high TIMP-1 expression on the invasive potential of NPA cells. Northern blot analysis showed that TIMP-1 mRNA levels correlated directly with tumour aggressiveness: the highest number of TIMP-1 transcripts was found in stages III and IV vs benign goitre (P < 0.0001). However, TIMP-1 expression was not increased in NPA and SW579 cells, both of which are derived from poorly differentiated thyroid tumours. Immunohistochemical study showed strong TIMP-1 staining in the stroma cells of advanced stages of carcinomas. Overexpression of TIMP-1 by gene transfer resulted in a significant suppression of the malignant phenotype of NPA cells as judged by an in vitro tumour invasion assay. These results suggest that high levels of TIMP-1 transcripts in advanced stages of thyroid carcinoma likely come from stroma rather than thyroid cancer cells, and TIMP-1 may function as a thyroid tumour invasion/metastasis suppressor. © 1999 Cancer Research Campaig

Sex differences in oncogenic mutational processes

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Author Correction: Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing (Nature Genetics, (2020), 52, 3, (331-341), 10.1038/s41588-019-0576-7)

Correction to: Nature Genetics, published online 05 February 2020. In the published version of this paper, the members of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium were listed in the Supplementary Information; however, these members should have been included in the main paper. The original Article has been corrected to include the members and affiliations of the PCAWG Consortium in the main paper; the corrections have been made to the HTML version of the Article but not the PDF version. Additional corrections to affiliations have been made to the PDF and HTML versions of the original Article for consistency of information between the PCAWG list and the main paper

Author Correction: The landscape of viral associations in human cancers

Correction to: Nature Genetics https://doi.org/10.1038/s41588-019-0558-9, published online 05 February 2020

Author Correction: Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer

Correction to: Nature Genetics https://doi.org/10.1038/s41588-019-0564-y, published online 05 February 2020