Confronting an identity crisis - how to "brand" systems engineering

Systems Engineering is not a new discipline; the term has been in use since World War II. Yet, while there has been no shortage of definitions of the term over the years (not all of which are consistent), there is little consensus on the scope of Systems Engineering. This is particularly true in relation to other overlapping disciplines such as System Dynamics, Operations Research, Industrial Engineering, Project Management, Soft Systems Methodology, Specialist Engineering, and Control Theory, which share many of the origins and techniques of Systems Engineering. This paper presents a landscape of disciplines and suggests that INCOSE should “brand” Systems Engineering strategically, defining explicitly its position within this landscape including its points of parity (overlaps) and points of difference with other disciplines. Actively branding Systems Engineering will broaden its appeal and attract more interest from stakeholders outside the current Systems Engineering community. INCOSE’s “market share” relative to its biggest systems competitor—Project Management—is falling, so even though INCOSE membership is rising, more needs to be done to promote the profession

Elevated hemostasis markers after pneumonia increases one-year risk of all-cause and cardiovascular deaths

Background: Acceleration of chronic diseases, particularly cardiovascular disease, may increase long-term mortality after community-acquired pneumonia (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic state that occurs during an acute infection may increase risk of subsequent atherothrombosis in patients with pre-existing cardiovascular disease and increase subsequent risk of death. We hypothesized that circulating hemostasis markers activated during CAP persist at hospital discharge, when patients appear to have recovered clinically, and are associated with higher mortality, particularly due to cardiovascular causes. Methods: In a cohort of survivors of CAP hospitalization from 28 US sites, we measured D-Dimer, thrombin-antithrombin complexes [TAT], Factor IX, antithrombin, and plasminogen activator inhibitor-1 at hospital discharge, and determined 1-year all-cause and cardiovascular mortality. Results: Of 893 subjects, most did not have severe pneumonia (70.6% never developed severe sepsis) and only 13.4% required intensive care unit admission. At discharge, 88.4% of subjects had normal vital signs and appeared to have clinically recovered. D-dimer and TAT levels were elevated at discharge in 78.8% and 30.1% of all subjects, and in 51.3% and 25.3% of those without severe sepsis. Higher D-dimer and TAT levels were associated with higher risk of all-cause mortality (range of hazard ratios were 1.66-1.17, p = 0.0001 and 1.46-1.04, p = 0.001 after adjusting for demographics and comorbid illnesses) and cardiovascular mortality (p = 0.009 and 0.003 in competing risk analyses). Conclusions: Elevations of TAT and D-dimer levels are common at hospital discharge in patients who appeared to have recovered clinically from pneumonia and are associated with higher risk of subsequent deaths, particularly due to cardiovascular disease. © 2011 Yende et al

Regulators of genetic risk of breast cancer identified by integrative network analysis.

Genetic risk for breast cancer is conferred by a combination of multiple variants of small effect. To better understand how risk loci might combine, we examined whether risk-associated genes share regulatory mechanisms. We created a breast cancer gene regulatory network comprising transcription factors and groups of putative target genes (regulons) and asked whether specific regulons are enriched for genes associated with risk loci via expression quantitative trait loci (eQTLs). We identified 36 overlapping regulons that were enriched for risk loci and formed a distinct cluster within the network, suggesting shared biology. The risk transcription factors driving these regulons are frequently mutated in cancer and lie in two opposing subgroups, which relate to estrogen receptor (ER)(+) luminal A or luminal B and ER(-) basal-like cancers and to different luminal epithelial cell populations in the adult mammary gland. Our network approach provides a foundation for determining the regulatory circuits governing breast cancer, to identify targets for intervention, and is transferable to other disease settings.This work was funded by Cancer Research UK and the Breast Cancer Research Foundation. MAAC is funded by the National Research Council (CNPq) of Brazil. TEH held a fellowship from the US DOD Breast Cancer Research Program (W81XWH-11-1-0592) and is currently supported by an RAH Career Development Fellowship (Australia). TEH and WDT are funded by the NHMRC of Australia (NHMRC) (ID: 1008349 WDT; 1084416 WDT, TEH) and Cancer Australia/National Breast Cancer Foundation (ID 627229; WDT, TEH). BAJP is a Gibb Fellow of Cancer Research UK. We would like to acknowledge the support of The University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.345

Functional Analysis of a Breast Cancer-Associated FGFR2 Single Nucleotide Polymorphism Using Zinc Finger Mediated Genome Editing

The authors thank Barts Charity for funding and Breast Cancer Campaign for funding the Barts Breast Tissue Bank

Parallels, prescience and the past: analogical reasoning and contemporary international politics

Analogical reasoning has held a perpetual appeal to policymakers who have often drafted in historical metaphor as a mode of informing decision-making. However, this article contends that since the beginning of the ‘War on Terror’ we have arguably seen the rise of a more potent form of analogy, namely ones that are selected because they fulfil an ideological function. Analogical reasoning as a tool of rational decision-making has increasingly become replaced by analogical reasoning as a tool of trenchant ideologically-informed policy justification. This article addresses three key areas which map out the importance of analogical reasoning to an understanding of developments in contemporary international politics: the relationship between history and politics, in intellectual and policy terms; a critical assessment of the appeal that analogical reasoning holds for policymakers; and the development of a rationale for a more effective use of history in international public policymaking

Occupancy maps of 208 chromatin-associated proteins in one human cell type

Transcription factors are DNA-binding proteins that have key roles in gene regulation. Genome-wide occupancy maps of transcriptional regulators are important for understanding gene regulation and its effects on diverse biological processes. However, only a minority of the more than 1,600 transcription factors encoded in the human genome has been assayed. Here we present, as part of the ENCODE (Encyclopedia of DNA Elements) project, data and analyses from chromatin immunoprecipitation followed by high-throughput sequencing (ChIP–seq) experiments using the human HepG2 cell line for 208 chromatin-associated proteins (CAPs). These comprise 171 transcription factors and 37 transcriptional cofactors and chromatin regulator proteins, and represent nearly one-quarter of CAPs expressed in HepG2 cells. The binding profiles of these CAPs form major groups associated predominantly with promoters or enhancers, or with both. We confirm and expand the current catalogue of DNA sequence motifs for transcription factors, and describe motifs that correspond to other transcription factors that are co-enriched with the primary ChIP target. For example, FOX family motifs are enriched in ChIP–seq peaks of 37 other CAPs. We show that motif content and occupancy patterns can distinguish between promoters and enhancers. This catalogue reveals high-occupancy target regions at which many CAPs associate, although each contains motifs for only a minority of the numerous associated transcription factors. These analyses provide a more complete overview of the gene regulatory networks that define this cell type, and demonstrate the usefulness of the large-scale production efforts of the ENCODE Consortium

Neural Coding of Movement Direction in the Healthy Human Brain

Neurophysiological studies in monkeys show that activity of neurons in primary cortex (M1), pre-motor cortex (PMC), and cerebellum varies systematically with the direction of reaching movements. These neurons exhibit preferred direction tuning, where the level of neural activity is highest when movements are made in the preferred direction (PD), and gets progressively lower as movements are made at increasing degrees of offset from the PD. Using a functional magnetic resonance imaging adaptation (fMRI-A) paradigm, we show that PD coding does exist in regions of the human motor system that are homologous to those observed in non-human primates. Consistent with predictions of the PD model, we show adaptation (i.e., a lower level) of the blood oxygen level dependent (BOLD) time-course signal in M1, PMC, SMA, and cerebellum when consecutive wrist movements were made in the same direction (0° offset) relative to movements offset by 90° or 180°. The BOLD signal in dorsolateral prefrontal cortex adapted equally in all movement offset conditions, mitigating against the possibility that the present results are the consequence of differential task complexity or attention to action in each movement offset condition

Sinking Jelly-Carbon Unveils Potential Environmental Variability along a Continental Margin

Particulate matter export fuels benthic ecosystems in continental margins and the deep sea, removing carbon from the upper ocean. Gelatinous zooplankton biomass provides a fast carbon vector that has been poorly studied. Observational data of a large-scale benthic trawling survey from 1994 to 2005 provided a unique opportunity to quantify jelly-carbon along an entire continental margin in the Mediterranean Sea and to assess potential links with biological and physical variables. Biomass depositions were sampled in shelves, slopes and canyons with peaks above 1000 carcasses per trawl, translating to standing stock values between 0.3 and 1.4 mg C m2 after trawling and integrating between 30,000 and 175,000 m2 of seabed. The benthopelagic jelly-carbon spatial distribution from the shelf to the canyons may be explained by atmospheric forcing related with NAO events and dense shelf water cascading, which are both known from the open Mediterranean. Over the decadal scale, we show that the jelly-carbon depositions temporal variability paralleled hydroclimate modifications, and that the enhanced jelly-carbon deposits are connected to a temperature-driven system where chlorophyll plays a minor role. Our results highlight the importance of gelatinous groups as indicators of large-scale ecosystem change, where jelly-carbon depositions play an important role in carbon and energy transport to benthic systems