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Atherosclerosis, a chronic inflammatory disease of the vascular system, presents significant challenges to developing effective molecular diagnostics and novel therapies. A systems biology approach integrating data from large‐scale measurements (e.g. transcriptomics, proteomics and genomics) is successfully contributing to deciphering regulatory networks underlying the response of many different cellular systems to perturbations. Such a network analysis strategy using pathway information and data from multiple measurement platforms, tissues and species is a promising approach to elucidate the mechanistic underpinnings of complex diseases. Here, we present our views on the contributions that a systems approach can bring to the study of atherosclerosis, propose ways to tackle the complexity of the disease in a systems manner and review recent systems‐level studies of the disease.
Atherosclerosis and systems biology
Atherosclerosis is a complex multifactorial disease characterized by the accumulation of inflammatory cells, lipoproteins and fibrous tissue in the wall of large arteries (Lusis, 2000). It is the primary cause of heart attacks and strokes and thus is the underlying cause of the majority of deaths globally, accounting for approximately 29% of all deaths worldwide. Cardiovascular disease disproportionately affects low and middle income countries and is projected to remain the single leading cause of death worldwide for the next 20 years (World Health Organization, 2009). Despite the enormous economic and social burden of this disease, we lack both a full understanding of its underlying mechanism and the ability to personalize its diagnosis and treatment.
Research over the past several decades has revolutionized our understanding of the pathogenesis of atherosclerosis. Previously atherosclerosis was viewed primarily as a passive process of cholesterol accumulation in the vessel wall, and the clinical manifestations were attributed primarily to the degree of stenosis. We now understand that atherosclerosis is a complex and active process and that the ultimate clinical presentation results from the interaction of multiple cell types and organ systems (Corti et al, 2004; Libby & Theroux, 2005). Because of its underlying complexity, the study and treatment of atherosclerosis presents several fundamental challenges that the emerging discipline of systems biology is uniquely suited to address.
Systems biology is the comprehensive, quantitative analysis of the manner in which all of the components of a biological system interact over time (Zak & Aderem, 2009). To study atherosclerosis, one would for example consider the human body as the biological system and naturally, all the molecules, cells, tissues and organs that play a role in the pathology of this disease are its components. While systems biology is dependent on new 'omics'‐scale technologies, it is not defined by these technologies. Rather, the systems approach involves the integration of the data derived from these measurement tools into comprehensive predictive models.
Systems biology is hypothesis‐driven, global, quantitative, iterative, integrative and dynamic. Its practice begins with the acquisition of global sets of biological data from as many hierarchical levels of information as possible [i.e. deoxyribonucleic acid (DNA) sequences, ribonucleic acid (RNA) expression, protein or lipid abundance]. This is the starting point for formulating detailed graphical or mathematical models, which are then iteratively refined through a hypothesis‐driven process of system perturbation and data integration. Cycles of this process will result in more accurate models; ultimately, these models will explain the systems‐level properties of the biological system of interest. Once the model is sufficiently accurate and detailed, it will allow researchers to accomplish two tasks never before possible: (1) predict the behaviour of the system given any perturbation and (2) redesign or perturb the molecular network to create new emergent properties. Taking the atherosclerosis analogy further, a researcher or clinician could (1) predict the body's response to, for example, a new diet or medication and (2) design an appropriate intervention that prevents atherosclerosis‐promoting events or shifts them to anti‐atherosclerotic ones. This latter possibility lies at the heart of preventative medicine.
The levels of complexity of atherosclerosis
Atherosclerosis involves the interplay among thousands of molecules in multiple interacting cells types including macrophages, endothelial cells and smooth muscle cells (SMCs). The disease occurs in different forms throughout the body (Trogan et al, 2006) and is affected by inputs from multiple organ systems including the vascular system, the endocrine system, adipose tissue, the liver, the gastrointestinal tract and the kidneys (Fig 1). Epidemiologic and treatment studies have also shown that the disease is modulated by a variety of genetic and environmental factors (Yusuf et al, 2004). For example, alteration in the relative abundance of various plasma lipoproteins such as low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL) has been shown to be of primary importance in the development of the disease. The levels of these lipoproteins are influenced by multiple genetic factors (such as mutations in the LDL receptor gene which cause familial hypercholesterolemia (Brown & Goldstein, 1974) and mutations in the ABCA1 gene which cause Tangier disease (Rust et al, 1999) as well as diet, exercise and medications (Steinberg, 2004, 2005a, b, 2006). Many of the risk factors for atherosclerosis, including dyslipidemia, hypertension, diabetes and obesity, involve the interaction of several organ systems such as the liver, kidneys, gastrointestinal tract and hormonal systems (Assmann et al, 1999). Furthermore, systemic inflammation, which has been shown to be critically involved in both the development and eventual clinical complications of atherosclerosis, involves immune cells and mediators located at the site of plaque formation as well as distal organ systems such as the liver and adipose tissue (Libby et al, 2002; Ross, 1999). Thus, atherosclerosis results from the complex interplay of genetic and environmental risk factors at a whole‐organism level (Fig 1).
Atherosclerosis progresses through multiple stages from early fatty streaks, to advanced lesions to plaque rupture, with each stage being characterized by different cellular and molecular components (Fig 1D). Atherosclerotic plaque development begins with endothelial cell activation, including overexpression of leukocyte adhesion proteins such as vascular cell adhesion molecule 1 VCAM‐1 (Cybulsky & Gimbrone, 1991). Chemoattractants such as monocyte chemoattractant protein 1 (MCP‐1) then promote migration of leukocytes into the intima (Boring et al, 1998), where macrophage colony stimulating factor (CSF1) promotes the differentiation of monocytes into macrophages (Rajavashisth et al, 1990). These macrophages express scavenger receptors that allow them to engulf and modify lipoproteins and become foam cells which secrete inflammatory mediators [such as interleukin‐1 (IL‐1), tumour‐necrosis factor‐α (TNF‐α), nitric oxide and endothelin] (Hansson et al, 2006), that amplify inflammation in the vessel wall and can contribute to additional leukocyte accumulation, SMC proliferation and extracellular matrix remodelling (Brown & Goldstein, 1983; Greaves & Gordon, 2009). Multiple other leukocytes are recruited to the lesion and have been demonstrated to play a critical role in disease development (Weber et al, 2008). Whereas foam cell accumulation characterizes fatty streaks, deposition of fibrous tissue defines the more advanced atherosclerotic lesion. SMCs synthesize the bulk of the extracellular matrix that characterizes this phase of plaque evolution (Raines & Ferri, 2005). Plaque rupture resulting from inflammatory activation and the ensuing thrombosis commonly cause the most acute complications of atherosclerosis such as myocardial infarctions or stroke (Fuster et al, 2005).
There are multiple challenges facing clinicians in the treatment of atherosclerotic vascular disease. Atherosclerosis is a chronic condition that develops silently over decades, presenting with clinical manifestations only very late in the course of the disease. Current strategies to detect early disease rely heavily on population‐based risk factor assessment but lack the ability to individualize these risk assessments. Currently available diagnostic tools are only able to detect advanced disease. Furthermore, while many pharmacologic interventions directed at reducing correlative risk factors have been shown to reduce the population‐based cardiovascular mortality rate, no methods are currently available to track the vascular response in an individual patient and therefore to predict that patient's risk of future events. Thus, current strategies do not holistically address the multiple factors that contribute to the observed pathology.
Applying network analysis to atherosclerosis questions
Given the complexities of atherosclerosis, a systems biology approach that samples multiple levels of hierarchical data and then integrates the results into coherent network models offers many advantages. Complex biological networks are organized around sub‐networks of gene modules that contribute to the robustness of the entire system. From a systems‐level perspective, disease states represent perturbations, from genetic or environmental factors, on complex networks of interacting components on multiple scales (molecules, macromolecules, organelles, cells, tissues and organs).
The recent development of global measurement and analysis technologies, and their integration under the aegis of systems biology, offer an unprecedented opportunity to overcome the difficulties inherent in atherosclerosis research and treatment. The complex spatial and temporal relationships involved in the disease need to be understood in the context of a dynamic interaction network. Because atherosclerotic plaques evolve over time from simple fatty streaks to advanced lesions prone to plaque rupture, a useful model of the disease process must be able to accommodate changes in molecular composition and interactions over time. Below, we describe the use of interaction networks in systems biology and their application to atherosclerosis research.
A network is a framework that represents the relationships among the features that make up complex biological systems. Biological networks are made up of nodes, which represent molecular entities (such as DNA variations, RNA, proteins and metabolites), edges that represent the relationships between these entities, and network properties that represent the state of the molecular entities over time (Fig 2). The network topology represents all of the interactions involved in a given biological system. A cornerstone of the systems biology approach is the construction of a network representing the disease process, using a collection of methods that together can be called network analysis. Network analysis can help identify feedback mechanisms and network regulatory motifs that capture the emergent properties of the system, such as robustness to perturbation, multistability or homeostatic control.
Network analysis can be divided into two approaches, ad hoc network construction and pathway analysis. Both are useful for analysing expression data pertaining to a complex disease such as atherosclerosis, and they have complementary advantages and limitations. The pathway approach is more straightforward to interpret, but it is limited to only those biological functions and processes that are represented in a pathway database. Arbitrary divisions between canonical pathways can also limit the effectiveness of the pathway approach. On the other hand, the ad hoc approach has greater potential to reveal novel molecular connections within the data, but the networks generated in the ad hoc approach can be challenging to interpret. We outline a procedure and relevant resources for each approach below.
The pathway approach
In the pathway approach a network diagram is organized around curated lists of interactions known to be involved in a specific molecular process, for example, 'eicosanoid biosynthesis' or 'toll‐like receptor signalling'. These pathway‐oriented interaction networks can be obtained from freely accessible pathway repositories (Table 1) and from commercial pathway databases such as Ingenuity Pathways Analysis (IPA, Ingenuity), MetaCore (GeneGo) and Pathway Studio (Ariadne). There are also several freely available software tools that can mine multiple pathway databases (see Table 1). Beyond analysis in terms of separate pathways, an atherosclerosis dataset can also be analysed across multiple pathways to identify molecules or genes that operate within more than one atherosclerosis‐associated pathway (e.g. see Ghazalpour et al, 2004).
The ad hoc approach
As opposed to the pathway approach, the ad hoc approach is unbiased. Here, differentially expressed molecules [ideally identified using a significance threshold that accounts for multiple hypothesis tests (Storey & Tibshirani, 2003)] are grouped into sub‐networks that are highly interconnected in an interaction dataset. Often, differentially expressed molecules may share an interacting partner that is not itself differentially expressed, such as a common regulator, substrate, etc. To reveal such indirect connections, molecules can be added to the network that, by virtue of their interactions, enhance the network's connectedness [e.g. its clustering coefficient (Watts & Strogatz, 1998)]. The ad hoc network construction approach does not rely on curated pathway information, but instead is applied using large databases of molecular interactions or associations. Most commonly used are databases of protein–protein interactions (PPI), protein–DNA interactions and protein–metabolite interactions. Interaction databases fall into two categories, large‐scale interaction repositories, which may aggregate interactions from high‐throughput PPI screens from various species and tissue types, and interaction databases that are focused on a specific class of molecules or functions. A listing of commonly used, publicly accessible interaction databases is given in Table 2. An important limitation of many of these databases is that they aggregate findings from a variety of model cell types, and thus the interaction data are not necessarily derived from atherosclerosis‐relevant tissues or models. Another caveat is that literature‐based interaction databases necessarily provide more information on better‐studied molecules, which may introduce bias into the network model.
Typically, ad hoc network analysis begins with a network constructed from a 'seed' collection of molecules identified in an expression study and any direct interactions between them. To this seed network are then added molecules that have high connectivity to the seed network, thus growing a highly interconnected molecular network in an iterative fashion. The resulting network can be analysed for enrichment of functional annotations to gain insight into its specific biological functions. Several software tools are available that can perform ad hoc network construction and analysis, as well as statistical and bioinformatic analysis of high‐throughput data (Table 3). Integrating data from different high‐throughput measurement platforms (e.g. transcriptomic and proteomic) can be particularly useful to comprehensively detect disease‐associated genes, and statistical approaches have been specifically developed to iteratively expand a molecular network using multiple data types (Hwang et al, 2005).
Analysing large‐scale expression measurements in the context of molecular pathways or interaction networks can reveal key regulatory molecules and functional modules involved in the disease process and suggest hypotheses regarding the system response to perturbation. Originally used in the context of model organisms such as yeast and bacteria, ad hoc network analysis has more recently been applied to the study of mammalian systems. Particularly relevant to atherosclerosis, several studies have examined networks involved in the inflammatory response in macrophages. Gilchrist et al combined transcriptional profiling and analysis of promoter sequences to identify activating transcription factor 3 ATF3 as a regulator of macrophage response to the bacterial endotoxin lipopolysaccharide (Gilchrist et al, 2006). Based on the network analysis, ATF3 was predicted to act as a negative regulator of Toll‐like receptor 4 TLR4‐induced expression of key pro‐inflammatory genes such as Il6 and Il12b, and this prediction was validated both in vitro and in vivo. A second transcriptomic study analysed the dynamic transcriptional response of macrophages to stimulation with various Toll‐like receptor TLR agonists. Using a probabilistic framework, transcriptomic data were integrated with promoter sequence scanning (scanning for cis‐regulatory motifs from the TRANSFAC database) to predict transcription factors that regulate clusters of TLR‐responsive genes. TGFB‐induced factor homeobox 1 TGIF1 was identified as a potential novel transcriptional regulator of a cluster containing the cytokines Csf2 and Gm1960 (Ramsey et al, 2008).
Taking network analysis further
Network analysis can enhance the utility of even simple transcriptomic studies, as we illustrate in Fig 3. Expression data‐mining based solely on gene functional annotations is limited by incomplete annotations and the fact that key regulators of disease progression may not be differentially expressed. Furthermore, within a disease‐associated functional module, only a small fraction of molecular species may be differentially expressed. Network analysis can extend beyond gene annotation enrichment analysis by taking into account interactions between the molecules in the expression dataset (and intermediaries). Among other advantages, this enables the identification of regulatory molecules that may not be differentially expressed (Fig 3A). A differentially expressed molecule can also be identified as a candidate regulator based on its proximity to disease‐associated molecules in the interaction network (Fig 3B). Moreover, the sub‐network involving a differentially expressed molecule may indicate its significance, for example, if it resides in a feedback loop regulating the level of a disease‐associated protein or metabolite. As an example of this network‐oriented approach, we analysed transcriptomic data from murine macrophages treated with oxidatively modified LDL (oxLDL), a stimulus that is associated with foam cell formation. The analysis and the resulting network, which are detailed in Box 1 and Fig 4, show how a potential regulator of the response (p65/Rela) can be identified even though it is not differentially expressed. This simple example also reveals the potential for network analysis to provide a more complete picture of the cellular response than would analysing the annotations of only the differentially expressed genes. Moreover, network analysis can uncover network regulatory motifs [e.g. feedback loops, feed‐forward loops, etc. (Alon, 2007)] controlling the response.
BOX 1: Network analysis of macrophage response oxLDL.
As an example of network analysis, we analysed transcriptomic data from murine macrophages treated with oxLDL, a stimulus that is associated with foam cell formation. Using the PLIER algorithm (Affymetrix, 2005), 542 genes were identified as differentially expressed. Ad hoc network analysis was performed on the 542 genes using MetaCore, yielding a network (Fig 4) associated with three biological processes relevant to foam cell formation: 'regulation of foam cell differentiation' (P < 10−10), 'regulation of macrophage differentiation' (P < 10−9) and 'lipoprotein catabolic process' (P < 10−9). A functional enrichment test of only the differentially expressed genes in the network fails to detect these enrichments, because only a fraction of the molecules in the network are differentially expressed. The interaction network has multiple interactions with sphingolipids, consistent with the findings of Wheelock et al (2009) based on the data from Kleemann et al (2007).
The application of both pathway (Cagnin et al, 2009) and ad hoc (Skogsberg et al, 2008) network analysis has facilitated extraction of biologically meaningful information from microarray messenger RNA (mRNA) studies of atherosclerotic plaques. Such studies are critical in that they analyse disease‐relevant tissue [e.g. whole mouse aorta (Skogsberg et al, 2008) or human coronary and carotid arteries (Cagnin et al, 2009)] but they pose numerous analysis challenges. For example, the lesion samples contain a mix of cell types obtained at a fixed time point. These studies allow the construction of a 'parts list' of molecules that may participate in the process—which is extremely useful in the interpretation and analysis of complementary in vitro studies. However, to go beyond such lists requires the application of network analysis. By doing this type of analysis the authors provided insights into disease pathogenesis that would not otherwise have been apparent. For example, network analysis of transcriptional data from lesions suggested a small group of cholesterol‐responsive genes whose functional annotations were suggestive of involvement in lipid uptake or metabolism (Skogsberg et al, 2008). Screening this gene network with siRNA in an in vitro macrophage cholesterol accumulation assay showed that no single intervention ablates foam cell formation. These findings are consistent with the viewpoint that foam cell formation in vivo is likely to be resistant to targeting a single molecule, and instead may require a combined therapeutic approach.
Both pathway and ad hoc network analysis depend on the quality and comprehensiveness of the underlying interaction database. One approach to extend beyond the available databases is to construct networks using molecular associations based on semantic mining of relevant scientific literature. This has the advantage of enabling an investigator to explore networks organized around relevant biological search terms such as 'atherosclerosis', 'foam cell' or 'cardiovascular disease'. The interactions in these networks are based on co‐occurrence of molecule names within abstracts of disease‐associated articles, with the molecule names separated by a keyword that is suggestive of molecular interaction (e.g. 'binds', 'modifies', 'phosphorylates', etc.). This literature network approach has been used in the analysis mRNA profiles of human atherosclerotic tissue (Ashley et al, 2006; King et al, 2005). Due to limitations inherent in human studies, these investigations could not identify transcriptional markers of early‐stage disease, and they identified a relatively modest number of differentially expressed genes compared to controlled transcriptomic studies of lesions in mice. Integrating data from both human and model systems maximizes the probability of obtaining robust, physiologically relevant findings. Tabibiazar et al leveraged transcriptional data from mouse aortas and human coronary arteries to identify atherosclerosis‐related genes that are predictive of disease severity in mouse and lesion grade in human (Tabibiazar et al, 2005). Their analysis confirmed many genes whose transcript levels are known to correlate with disease severity and identified functional classes of genes that are novel in the context of atherosclerosis (such as RUNX transcription factors and histone deacetylases). Such a dual‐species approach has the benefit of ensuring that the transcriptional correlates of disease severity identified in mice are relevant in human.
Integrating transcriptomic, proteomic and metabolomic measurements into network analysis can yield a more complete picture of changes responsible for the initiation of atherosclerotic vascular disease than can be obtained by analysing a single measurement type. Applying such an approach in a mouse model of atherosclerosis has demonstrated the importance of transcriptional and metabolic reprogramming of the liver as a key driver of the inflammatory process underlying atherogenesis (Clish et al, 2004; Kleemann et al, 2007).
Examining a combination of genetic and transcriptomic measurements in the context of molecular pathways and biological processes associated with atherosclerosis has also been used as a novel method to uncover disease biomarkers (Hagg et al, 2008; Torkamani et al, 2008). For example, this approach identified insulin receptor substrate 2 (IRS2), whose expression is higher in macrophages from individuals with atherosclerosis than from control subjects. Through genetic association analysis of a larger cohort, a single nucleotide polymorphism SNP in the IRS2 promoter was identified that results in higher IRS2 gene expression and increased risk of coronary heart disease (Hagg et al, 2008). Thus, this approach utilizing a tiered study design has identified a potential novel biomarker for the development of coronary heart disease.
A number of excellent genome‐wide association studies (GWAS) have uncovered multiple genetic loci that are associated with the development of atherosclerosis (Assimes et al, 2008; Aulchenko et al, 2009; Erdmann et al, 2009; Jarinova et al, 2009; McPherson et al, 2007; Tregouet et al, 2009), the subsequent clinical complications of atherosclerosis such as myocardial infarction (Kathiresan et al, 2009a) as well as risk factors for atherosclerosis such as hypertension (Newton‐Cheh et al, 2009), dyslipidemia (Kathiresan et al, 2007, 2008a, b, 2009b) and obesity (Lindgren et al, 2009; Willer et al, 2009). These studies demonstrate the power of current high‐throughput technologies as they have revealed multiple loci that would not have been uncovered with more traditional hypothesis‐based methods.
However, the utility of these studies is limited by the fact that GWAS does not necessarily directly indicate the causal gene and does not establish the biological context in which the causal gene operates. The integration of GWAS data with studies that examine the downstream changes in the RNA, protein and metabolite state has the potential to reveal the perturbations in molecular networks that are associated with disease. Additional discovery power can be achieved through integration of QTL and transcriptional profiling analysis of strain‐intercrossed mice with varying susceptibility to atherosclerosis (Smith et al, 2006a, b).
The identification of the macrophage‐enriched metabolic network (MEMN) is an excellent example of the power of such integrated approaches. This network was constructed by integrating multiple data types including genetic studies and expression data from human and mouse liver and adipose tissue (Chen et al, 2008; Emilsson et al, 2008). The MEMN was strongly associated with obesity, diabetes and heart disease and this was confirmed experimentally in studies that indicate complex feedback control within the network (Mehrabian et al, 2005; Schadt et al, 2008; Yang et al, 2009). These studies identified several genes, including a newly discovered phosphatase gene Ppm1l, that were associated with multiple cardiovascular risk factors including weight, glucose tolerance, levels of free fatty acids and blood pressure. Additionally, these studies suggested that the macrophage not only plays a key role at the local level in the plaque but that it is also a driver of many complex metabolic diseases that are associated with atherosclerosis (Schadt, 2009).
This body of literature has made substantial contributions to the study of atherosclerosis. By increasing our ability to extract biologically meaningful information from high‐throughput data sets, network analysis has allowed the identification of potential novel therapeutic targets and diagnostic markers. Moreover, studies that publish complete high‐throughput data sets are particularly valuable to the research community because they enable other investigators to mine the data and formulate novel testable hypotheses.
Toward a systems‐level disease model
The network analysis tools and methods described above can be extended and refined to accommodate complex study designs spanning multiple tissues. This is particularly relevant to atherosclerosis, where available models of plaque formation and leukocyte infiltration necessarily involve a trade‐off between ease of expression profiling and physiological relevance. Network analysis can be performed on data from multiple expression studies, for example, from studies using different models or using different high‐throughput measurement platforms. We briefly mention two possible strategies. (i) Differential expression data across multiple studies can be clustered and the clusters used as 'seed' lists for ad hoc network construction. This approach is predicated on the hypothesis that clusters derived from data from multiple complementary expression studies (which will have different model artefacts and 'blind spots') will enable the construction of a more physiologically relevant network than would be possible using a single expression study. (ii) Present/absent detection calls for gene expression from more physiological models can be used to constrain the list of possible molecules for network construction. We believe this is a particularly promising strategy for extracting maximal information from in vitro expression studies using in vivo‐derived expression data.
Although the application of systems biology to the study of complex diseases is in its early stages, these studies are already providing novel insights into atherosclerosis and powerful tools to continue to decipher the intricacies of this disease. The promise of a systems approach includes disease prediction and prevention as well as personalized medicine.
A steroid metabolite found in cell membranes. It is transported in the blood in lipoprotein particles and excess circulating cholesterol is associated with atherosclerosis.
Pattern‐finding in a large dataset.
Familial hypercholesterolemia
A genetic disorder usually caused by mutations in the LDL‐receptor or in ApoB that results in high levels of LDL and premature atherosclerosis.
Fatty streak
Early atherosclerotic lesion containing mainly cholesterol and macrophages.
Feedback loop
A network motif in which a node (molecule) indirectly (or directly) regulates itself.
Feed‐forward loop
A network motif in which a node (molecule) both directly and indirectly regulates a downstream target node.
High density lipoprotein (HDL)
High density lipoprotein (HDL)—'good cholesterol', high levels are thought to be protective against atherosclerosis.
Low density lipoprotein (LDL)
Low density lipoprotein (LDL)—'bad cholesterol', high circulating levels have been shown to correlate with atherosclerosis.
The buildup of cells and cholesterol in the arterial wall. Severe plaque buildup can narrow the arterial lumen interfering with the flow of blood.
A group of nodes (molecules) used as the starting point in ad hoc network construction.
The abnormal narrowing of an artery.
Tangier disease
A genetic disorder resulting in very low levels of HDL caused by a mutation in the ABCA1 transporter.
Formation of a blood clot.
For more information
American Heart Association:
European Atherosclerosis Society:
United States National Heart Lung and Blood Institute:
International Atherosclerosis Society:
Systems Immunology website:
Lipid MAPS project website:
Systems Biology portal:
Author's website:
We thank Alan Diercks for helpful comments. The authors acknowledge support from NIH contract HHSN272200700038C (National Institute for Allergy and Infectious Diseases). S.A.R. was supported by Award Number K25HL098807 from the National Heart, Lung and Blood Institute.
The authors declare that they have no conflict of interest.
- Copyright © 2010 EMBO Molecular Medicine


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After the moves 1.e4 e5 2.Nf3 Nc6 3.Bb5 a6 4.Ba4 Nf6 5.0–0 b5 6.Bb3 d6, it seems that 7.c3! must be the critical test.
Now d4 is no longer available for Black's knight and 8.Ng5 is becoming more of a threat.
Now d4 is no longer available for
Black's knight and 8.Ng5 is
becoming more of a threat.
This is Black's most popular follow up and removes pressure from the sensitive f7-pawn. In a reply to my 7.Ng5 entry, Phil Adams brought to my notice that Soltis in his new book ' Transpo Tricks in Chess' (Batsford 2007) briefly discusses this move-order. Obviously Bisguier used it mainly as a confusing transposition tool against Robatsch in Hastings 1961, here playing 7...Be7. That allows White to look for ways to omit or delay Re1 (as the e4-pawn is already protected by Bc2), but the White rook will be nicely placed on e1 so it will normally quickly transpose to a mainline Closed Ruy Lopez.
I had a look at 7...g6 8.Ng5 d5 9.exd5 but did not find anything that really looked playable for Black.
7...Bg4 is another active move that keeps open the option to develop with ...g6. Unfortunately it seems White can keep an edge with little risk:
a) 8.Qe2 mainly has historical interest: 8...Be7 9.Rd1 Na5 10.Bc2 c5 11.d3 Nc6 12.h3 Bd7 13.d4 += Stoltz-Alekhine, Salzburg 1942.
b) 8.Re1 is the start of a familiar plan for most players of the white side of the Ruy Lopez. White hopes to demonstrate that the active bishop mainly is a target and will play d3, Nbd2-f1-g3 and only then put the question to the bishop with h3. A relevant game went 8...Na5 9.Bc2 c5 10.d3 g6 11.Nbd2 Bg7 12.Nf1 0–0 13.h3 Bd7 14.Bg5 h6 15.Bh4 Qc7 16.Ne3 Be6 17.d4 Nc4 18.Nxc4 Bxc4 19.d5 b4 20.cxb4 g5 (20...cxb4 21.Ba4 +=) 21.Bg3 cxb4 22.Qd2 with some advantage to White in Unzicker-Bisguier, IZ (Gothenburg) 1955.
8.Bc2 c5
This increases Black's central presence, allows him to support his central pawns with ...Qc7 and seems generally consistent with his previous move. Still, b4 doesn't seem to be much of a threat yet, so I wonder if 8...g6 9.d4 Qe7 may be a possibility.
9.d4 Qc7
This seems necessary in order to support Black's central presence (but seen in light of the further course of the game you may wonder if 9...Qe7, planning ...g6 is an option).
This appears to be the critical move, and only if Black can pass this test he needs to worry about the alternatives 10.Re1, 10.h3 and 10.a4.10...g6!?
Well, this bishop development was Black's main idea. However, it's worth noting that one of Kuzmin's latest games with the line went 10...cxd4 11.cxd4 Bd7 12.Bd3 Be7 13.Qe2 0–0 14.b3 Nc6 15.Bb2 Bd8 16.a4 bxa4 17.dxe5 Nxe5 18.Nxe5 dxe5 19.bxa4 Bg4 20.Qe3 Be6 when the players agreed a draw even if White had the more comfortable position in Kindermann-Kuzmin, Panormo 2001.
Only this non-stereotyped move can cast doubt on Black's idea. 11.a4 b4 12.cxb4 cxb4 13.b3 exd4 14.Nxd4 Bg7 15.Bb2 0–0 16.Rc1 Nd7 17.Bb1 Qb6 was fine for Black in Vasiukov-Kasparian, Yerevan 1955.
11...cxb4 12.cxb4 Nc6 13.Bb2 Bg7
Actually the optimistic 13...Nxb4 14.Bb1 Nc6 seems playable but after 15.Qc2 Qb6 16.dxe5 dxe5 17.Nxe5 Nxe5 18.Bxe5 Bg7 19.Nb3 0–0 20.Bd4 White's advantage is fairly obvious.
Black's queen is exposed in the open c-file so this is a natural reaction. Black has also tried:
a) 14...Bb7? 15.Bb3 Qe7 16.Rxc6! Bxc6 17.dxe5 Nh5 18.g4 Nf4 19.exd6 +- Bronstein-Evans, Moscow 1955.
b) 14...0–0 15.Bb3 += was our conclusion in 'The Ruy Lopez: A Guide for Black', but on closer inspection it seems that Black has some quite serious problems: 15...Qb6 16.dxe5 dxe5 17.Nxe5 Nxe5 18.Bxe5 Bg4 19.Qc2 Rae8 and now Suetin-Ragozin, (URS Ch) Kiev 1954 was drawn after the moves 20.Qc7 Qxc7 21.Bxc7 Bh6 (this position is equal) 22.Rc6 Bxd2 23.Rxf6 Be2 24.Bd6 Bg5 25.Bxf8 Bxf6 26.Re1 Rxe4 27.Bc5 Bc3 28.f3 Bxe1 29.fxe4 Kg7. However, after 20.Qb2 Black has problems freeing his position.
15.Bb3 Nxd4
15...Bb7 16.a3 0–0 17.d5 Nd8 18.Rc3 gives White a clear advantage.
16.Nxd4 exd4 17.Bxd4 0–0 18.Re1 Be6 19.Nb1
Or 19.Bxe6 Qxe6 20.a4 with a small plus for White.
19...Bxb3 20.axb3
Now White will have some pressure down the semi-open a-file but his b-pawns are weak. I am not sure why White preferred this over 20.Qxb3 which seems to preserve a small advantage.
20...Nh5 21.Bxg7 Kxg7 22.Rc6 Rfd8 23.Nc3 Nf6 24.Qa1 Qe5 1/2–1/2 Vasiukov-Arulaid, Voroshilovgrad 1955.
It seems Black has a slightly harder task to equalize after 6...d6 7.c3 than in the Closed Ruy Lopez mainlines, but that to some extent should be compensated by the element of surprise. It would also be interesting to see a high level game with 9...Qe7.


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Identification badges have been made and given to courthouse employees, but each department head has discretion about whether to require that they be worn.
Identification badges have been made and given to courthouse employees, but each department head has discretion about whether to require that they be worn.
The Etowah County Commission could vote next week to make it mandatory for all employees to wear the badges inside the building.
The badges do not include a security pass code for doors but would identify someone who is a courthouse employee. Employees have been given the badges, personnel director Jennifer Taylor said. She said the current policy leaves wearing the badges at the discretion of each department head and any discipline for not wearing them at the department head's discretion as well.
"It should not be a department issue," Commissioner Kenney Tidmore said. "It's a county commission issue."
Etowah County Revenue Commissioner Linda Barrett Vaughan said she already requires employees in her department to wear badges, and it has not been a problem. It's an easy way to identify someone who works in the building.
She said she believes all employees should wear them anytime they're in the building — even after regular business hours.
She said she is sometimes at her office after hours and has seen people in the courthouse she does not know. She is not sure if the person is an employee in another department. If everyone wore a badge all times, at least the person could be identified as an employee.
It also would help the public identify anyone who is an employee, Tidmore said.
District 5 Commissioner Carolyn Parker said security is an issue at the courthouse.
"We need to look at more issues than a badge for security in this courthouse," Parker said. "A badge is not going to make you safer."
But requiring badges for identification is a good place to start, Tidmore said.


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In Action
Extreme Cave Exploration
The Demands of Extreme Exploration
Halcyon was created in response to the demands of extreme technical diving. In the early 1990s, Halcyon founders were exploring deep wrecks and long-distance caves, including world-renowned Wakulla Springs. No other site can draw the comparison of being the Mt. Everest of cave diving: massive conduit (often over 100 feet in diameter), deep, multi-branching passages, and passages explored to nearly 30,000ft/10km. Dives in Wakulla are the longest ever done: bottom times for the lead team can exceed 10 hours at a depth of 300ft/90m. By the time the team exits the water, they will have spent nearly 30 hours underwater.
Deep wrecks and long-distance cave diving are both physically and mentally demanding. Halcyon CEO Jarrod Jablonski has invested nearly 20 years leading just this sort of extreme expedition in projects around the world. As Global Underwater Explorers (www.gue.com) President and the lead Woodville Karst Plain explorer, Jarrod Jablonski has more exploration dives in Wakulla than anyone alive. In fact, Halcyon was founded in large part to be able to provide the gear he needed to make the dives as safely as possible. Casey McKinlay also joins Jarrod and teams of explorers for expeditions across the globe. Casey is the WKPP Project Director and oversees the planning for each exploration dive weekend. Over the course of these projects, dozens of divers spend hundreds of hours in a range of extreme underwater settings.
Exploration divers who push the limits of underwater exploration demand that their Halcyon equipment performs flawlessly. This dedication to quality is at the heart of Halcyon's quest to produce the best possible equipment and then to back it up with technical support starting the moment it leaves the factory. Regardless of your personal diving interest, you can be assured every piece of Halcyon equipment is designed with this same emphasis on quality and reliability.


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Purple House provides dialysis in the most remote parts of Australia
Purple House is an innovative Indigenous-owned and run health service operating from its base in Alice Springs in the Northern Territory Now operating 14 remote clinics and a mobile dialysis unit called the Purple Truck, Purple House is getting patients back home so that families and culture can remain strong.
Remote Indigenous people in Central Australia are up to 30 times more likely to suffer from kidney disease.
Families must move off their country and come to Alice Springs or Darwin for dialysis treatment. Communities are left without elder leadership, families are broken and culture is weakened. Patients suffer from isolation and depression, restricted by a dialysis machine for their foreseeable future.
Purple House is a home away from home for these Indigenous dialysis patients.
Purple House's Bush Balms products are made from plants expertly collected on Aboriginal lands around Central Australia.
Developed by people with an unbroken tradition of Indigenous intellectual and cultural knowledge, Bush Balms are truly made from the heart, offering employment opportunities for our renal patients and their families.
Purple House holds its first conference Share a Tale
In April 2019, Purple House held its first-ever conference, Share a Tale at the Alice Springs Convention Centre in Alice Springs. More than 50 delegates joined us from around Australia for this special conversation about remote dialysis, community-led healthcare and...
The Purple Truck on Australian Story!
The Purple Truck was featured on ABC Television's Australian Story on Monday 18 February 2019, alongside legendary Australian actor Jack Thompson.The program tells the story of Jack coming to terms with his diagnosis of kidney disease in early 2018. It...
Purple House wins NT Telstra Business Award
Purple House is the 2018 NT Telstra Business of the Year as announced at a ceremony in Darwin in August.
Recognised for being a strong Indigenous-run and controlled organisation, Purple House provides dialysis in 14 remote clinics as well as the Purple Truck, a mobile dialysis service.
Purple House exists because of the support of people like you!
As we are a registered charity, donations over $2 are tax deductible.
Your donations helps us get more people well and back home on country.


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Wednesday, October 12, 2011
Mexican Star
(Click to enlarge)
Labels: Mexican Star
5 comments:
Oh your mexican star is just wonderful. I love the colors that you picked for it. Yesterday was alot of fun. You are messy!!! Lol, me too,though.
- Wed Oct 12, 05:00:00 PM 2011
- carol fun said...
LOVE that batik - gorgeous colors. This is going to be a stunning quilt. And a day spent sewing with friends is a wonderful day!
- Wed Oct 12, 05:17:00 PM 2011
- Sue said...
Really beautiful! I do love the fabrics you chose for the Mexican Star. I have never heard of this pattern before so thank you so much for sharing it:)
Hope you are enjoying this wonderful autumn we are having!
- Wed Oct 12, 05:18:00 PM 2011
- Stray Stitches said...
What a beautiful pattern. The colors you selected are gorgoeous!!
- Wed Oct 12, 05:26:00 PM 2011
- Janet said...
This is so pretty. I love batiks too.
- Wed Oct 12, 09:26:00 PM 2011
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Oil spill off the coast of the Great Bear Rainforest- Canada
Originally published by the David Suzuki Foundation.
An oil spill was reported yesterday off the coast of the Great Bear Rainforest. There are 700 tonnes of heavy oil in a sunken U.S. Army ship under the site of the oil slick. While the current extent and severity of this oil spill is not yet known, there is potential for a significant spill.
What we do know is that 40% of the local diet comes from the sea, and that traditional shellfish harvesting areas are under threat.
Back in 2006, the federal government made assurances that the wreckage would get cleaned up, but they have done nothing since. Nearby, The Queen of the North (a BC ferry that sunk in 2006) also contains over 200,000 litres of fuel. Future leakages from either ship could severely impact local seafood, marine life and water quality.
These are just two reasons why we need better management of our oceans. This incident highlights the importance of taking a good comprehensive look at what we're doing in the ocean-and how we're doing it — to ensure that all measures are in place to ensure that coastal communities, businesses and ecosystem remain healthy.
Continue reading article on the David Suzuki Foundation.


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Okeana in Butler County, Ohio — The American Midwest (Great Lakes)
1858 Morgan Township House / Copperheadism in Butler County
Side A:
1858 Morgan Township House
On April 20, 1857, the trustees of Morgan Township met in Okeana to obtain a lot for the township house. From a quarter mill tax levy, $850 was budgeted for a house and lot. Money expended on the project included $50 for the lot, $650 for the construction of the building, $41 for fencing, $12.60 for twelve chairs, and $10.25 for a table. Since its completion in 1858, this meeting house has been used for trustee meetings, a voting precinct, village singing schools and concerts, public school, bank, and township garage. The trustees moved to a new building across the street in 1972 and into their Chapel Road complex in 2000.
Side B:
Copperheadism in Butler County
By the early summer of 1863, many Ohioans had become dissatisfied with what seemed a protracted Civil War. They opposed the administration of President Abraham Lincoln and the policy of a national military draft and were alarmed by what they saw as an invasion of their civil liberties. This was in part fueled by the arrest of Clement Vallandigham, future Democratic candidate for Governor, for publicly criticizing
Erected 2007 by Morgan Township Trustees, Morgan Township Historical Society, The Ohio Historical Society. (Marker Number 26-9.)
Marker series. This marker is included in the Ohio Historical Society / The Ohio History Connection marker series.
Location. 39° 20.888′ N, 84° 46.006′ W. Marker is in Okeana, Ohio, in Butler County. Marker is on Okeana-Drewersburg Road 0.1 miles west of Cincinnati-Brookville Road (Ohio Route 126), on the right when traveling west. Touch for map. Marker is opposite Okeana United Methodist Church. Marker is at or near this postal address: 6464 Okeana-Drewersburg Road, Okeana OH 45053, United States of America. Touch for directions.
Other nearby markers. At least 8 other markers are within 6 miles of this marker, measured as the crow flies. Founding Members of the Morgan Township Fire Department (approx. 1½ miles away); Birthplace of William Bebb Paddy's Run (approx. 3.2 miles away); Snow Hill Covered Bridge (approx. 4.8 miles away in Indiana); Bunker Hill / Dog Town (approx. 5.3 miles away); Bunker Hill Universalist Church/Bunker Hill Cemetery (approx. 5.3 miles away); Bethel Chapel (approx. 5.7 miles away); Bethel Chapel 1815- 1873 (approx. 5.7 miles away). Touch for a list and map of all markers in Okeana.
Categories. • Charity & Public Work • Civil Rights • Government • Notable Persons • Peace • Political Subdivisions • Politics • Settlements & Settlers • War, US Civil •
Credits. This page was last revised on June 16, 2016. This page originally submitted on November 2, 2009, by William Fischer, Jr. of Scranton, Pennsylvania. This page has been viewed 1,427 times since then and 11 times this year. Photos: 1, 2, 3, 4. submitted on November 2, 2009, by William Fischer, Jr. of Scranton, Pennsylvania.


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STORY: Damaris Chance's unhappy past has turned her off the idea of marriage forever. But her guardian, Lady Beatrice Davenham, convinces her to make her coming out anyway—and have a season of carefree, uncomplicated fun. When Damaris finds herself trapped in a compromising situation with the handsome rake Freddy Monkton-Coombes, she has no choice but to… Continue reading 'The Winter Bride' by Anne Gracie
Tag: His Captive Lady
Children and Animals in Books by Anne Gracie
W.C. Fields said "Never work with children or animals," and for a lot of people that holds true for romance books, too. Some readers really dislike having children or animals in books, others love them. Me? I say it's all in the execution. Sweetly lisping precocious bratty-type children? Little saintly critters? Generally no — though I… Continue reading Children and Animals in Books by Anne Gracie
'The Autumn Bride' by Anne Gracie
STORY: Governess Abigail Chantry will do anything to save her sister and two dearest friends from destitution, even if it means breaking into an empty mansion in the hope of finding something to sell. Instead of treasures, though, she finds the owner, Lady Beatrice Davenham, bedridden and neglected. Appalled, Abby rousts Lady Beatrice's predatory servants and—with… Continue reading 'The Autumn Bride' by Anne Gracie


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Rectifying Xsession boot up issue due to corrupt software installation
Novell Cool Solutions: Trench
By R Mohamed Razikh Ulla
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Posted: 8 Sep 2005
This Cool Solution is intended to provide information on rectifying the Xsession boot up issue.
ProblemThe Xserver session gets corrupted, due to the installation of any software which registers itself to the Xserver startup script.
To identify the problem, notice that the following error message is displayed during login:
"Your Session is lasted less than 10 seconds. If you have not logged out yourself, this could mean that there is some installation problem or that you may be out of diskspace. Try logging in with one of the failsafe sessions to see if you can fix the problem"
One possibility for this error coming up could be installation of software which is not meant for SUSE or Novell Linux Desktop distributions. For example, software like Yahoo messenger, when installed with the option to register at startup can result in this error.
SolutionProcedure to follow below:
- Login to your machine through any failsafe session
- Search in your home directory for .xinitrc file, then delete it.
- Logout of the current session, then login through normal X session.
Novell Cool Solutions (corporate web communities) are produced by WebWise Solutions. www.webwiseone.com


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Another good news form Cebu Pac!
No more fuel & insurance surcharge for Cebu Pacific domestic flights
First Philippine carrier to remove surcharges
Cebu Pacific (CEB), the Philippines' leading low-fare airline, removes fuel and insurance surcharges for all domestic flight bookings starting January 7, 2009.
Candice Iyog, CEB spokesman, said, "We are committed to offering the public the most affordable fares coupled with the newest planes. In fact, we have made air travel a viable option for those who would normally travel by bus or ferry. We will continue to give EveryJuan more reasons to fly as we expect to take delivery of six brand new aircraft in 2009."
Iyog explained that the removal of fuel and insurance surcharges will now allow passengers to easily compare airfare with the fares of buses and ferries.
The airline also cuts its fuel and insurance surcharge for select international routes. CEB's Manila-Bangkok and Clark-Bangkok one-way surcharges are slashed from USD80 to USD50 and USD80 to USD60, respectively.
Moreover, CEB's Manila-Osaka one-way surcharges are lowered from USD110 to USD100 and Manila-Hong Kong surcharges are reduced from USD45 to USD40 per way.
Iyog concluded, "We encourage everyone to book their flights via www.cebupacificair.com , call the reservations hotline (632) 70-20-888, or visit their nearest travel agents."
CEB has the most number of inter-island routes and connections from its hubs in Clark, Manila, Cebu and Davao. It will fly to 28 domestic destination and 15 international cities.
Got the news here.


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Book Now Add to shortlist
Starts at: 11:00
Finishes at: 15:00
Our College Road campus will be open, including workshops, studios and social areas.
Hereford, England
Yes, booking needed
Please note that these Open Days are for all our BA (hons) degree courses, except BA (Hons) Artist Blacksmithing, which has separate open days to include a visit to the forge.
Select a date for open day details and booking information
Get the latest news and updates


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BIG NEWS, Courtesy of the Anacostia Trust:
"Tara Morrison will take over as Superintendent of National Capital Parks–East on December 7. She will be responsible for Anacostia Park, historic homes (Frederick Douglass, Mary McLeod Bethune and Carter G. Woodson), the Fort Circle parks, and several other parks in DC and Maryland.
According to the release announcing her appointment, New Superintendent Named for Anacostia Park, Historic Homes and Capitol Hill Parks, Morrison will be joined by two new staff focused on Anacostia Park, a Project Executive for the Anacostia and a Senior Project Manager. The former will move forward Anacostia Park projects, partnerships, and initiatives. The latter will focus on cleaning five contaminated sites along the Anacostia River and will work closely with DC's Department of Energy and the Environment.
"Superintendent Morrison brings to National Capital Parks East a reputation of working effectively with park partners" noted Anacostia Waterfront Trust Executive Director Doug Siglin. "We look forward to working closely with her for many years to make the Anacostia Park truly a special place for all DC, but particularly for people who live east of the Anacostia River."
Morrison joined the National Park Service in 1998. She is not new to DC. Since 2011, Morrison has been Superintendent of Rock Creek Park. Throughout her NPS career, Morrison has engaged with community in a variety of ways. She has, for example, worked closely with the public during the creation of the African Burial Ground Visitor Center's first general management plan to ensure that the community was actively engaged in the process.
Morrison attended Northeastern University and received a B.S. in African American studies. She pursued graduate studies in anthropology at the University of South Carolina.
Morrison is taking the place of Gopaul Noojibail; Noojibail has moved to Wyoming to serve as Deputy Superintendent at Grand Teton National Park."


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Penguin Composites originally started as a watersport manufacturing business in 1976. The business now specialises in manufacturing composite components from various polyesters, isothalics, vinylesters and epoxies combined with composite products of various fibres and core materials to a broad base of industrial, commercial and domestic markets.
As a go to problem solver and product development specialist, Penguin Composites works both in house and onsite. The business is also supported by a metal workshop producing products for our recreational caravan and campervan business.


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The Dallas music scene lost a pillar today in Claude Johnson. He had been suffering health issues for the last few years. He was currently on dialysis treatment. Johnson studied at UNT in the late 60s and went on to play with players like Marchel Ivery, James Clay, Worm, Shelley Carrol, Martha Burks, James Lynn Marsh and other Texas greats. Although he did not record much as a leader, he was a mainstay in arranging for many jazz players. He will be missed by so many. Rest in Peace.
Keep in touch with us!
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Please be social with us!
Great ways to stay in touch!


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Lake Champlain Chocolates- 9pc. Truffles
Product Description
Experience the best chocolate truffles — made from Vermont butter, fresh cream, and smooth Belgian chocolate. With every bite, their delicate chocolate shell gives way to creamy ganache that melts on your palate. So good, you'll have to tell your friends . . . or surprise them with their very own box! Browse and buy online, then we'll ship your gift of truffles directly to you or a lucky recipient.


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I read an article today on Cinemagraphs and thought it was very cool concept. Basically taking a still photo and animating a portion of the photo. I'm providing a link to this article for you to review. Cinemagraph Article on Tripwire magazine – http://www.tripwiremagazine.com/2011/07/cinemagraphs.html
A few weeks ago, I took a series of photographs at McKinney State Park of the Falls. 9 photos I took by mistake, when I held the shutter release down for 9 shots. Fortunately for me, I kept them and was able to use them for my first Cinemagraph.
Here is my 2nd attempt
So here is my first attempt.
It was a lot of work, but it was a learning experience I enjoyed. I did have to spend a lot of time in front of the computer editing, which sometimes makes me worry because I know how detrimental it can be to sit down for long stretches of time. I try to do what I can though. I exercise whenever possible and I try to watch what I eat. I even take a great natural health supplement which has been working great for me, and I highly recommend it . If you would like to see if it is right for you, you can find out here.
If your expecting a detailed technical review, go ahead and stop now. I'm not going to tell you about all the features and functions that the Sony NEX-7 has and can do. I'm going to discuss my experience and impressions of the NEX-7 these past 5 weeks.
Let me start by giving some background on my decision to purchase the Sony NEX-7. I currently own a Nikon D90 with a lot of Nikon Glass. I thoroughly have enjoyed taking photos with the Nikon D90 for about 27 months. I've learned a lot about how to use it, take some wonderful photo's on vacations, of my children, friends, families, couples, landscapes. In all I've taken about 14,000 photo's with the D90. I want to get the new Nikon D800, saving my pennies for my real "Professional Quality" Camera. It is a little pricy at $3000, but I still plan on getting one after the summer and most importantly after paying for Summer vacation to Mexico this year.
So I almost forgot to write something today as I continue to write about my journey to taking better photo's and sharing them with you. So it is 11:55 at night, it was a long day at work, so I really didn't want to write anything, but felt I needed to write something, since it is my goal to write something every day.
So the topic is Flash Photography. I will probably write a future article about Flash Photography, as this can take volumes. So there are a couple of tips on flash photography. I will update a future entry and give some examples of what I'm going to discuss today, but I really don't have anything good in my portfolio that illustrates what I'm going to mention here, so you'll have to take my word for it.
White Balance, what is that?
If you haven't heard of White Balance, it means you probably haven't read your Manual. If you read in my last post, we discussed using Manual Mode to set the correct Exposure Level through the ISO, Aperture, and Shutter settings. Well White Balance (WB) is something that is very important when you take a photo with a Digital Camera.
In the previous post, we discussed ISO, Aperture, and Shutter Speed. We had just taken a photo with a fast shutter speed and everything was perfect!
Well not so fast. Remember when I mentioned that the key to a perfect photo was getting the correct Exposure Level or the correct amount of light into the camera Sensor? Well just because you set the Shutter Speed to 1/150 sec, doesn't mean you allowed enough light into the camera Sensor. It is actually possible that the photo may be to dark, especially if the photo was taken late in the afternoon, when the sun wasn't at it's brightest. So the real question is, "How do I allow enough light into the lens to the Camera Sensor to make that perfectly sharp photo?".
The most important thing I have learned when taking photos is learning how to use your camera. By this I mean, learning to using the Manual Mode, usually there is a dial on the camera that has an M on it, this is manual Mode. You will probably see additional letters and pictures on this, stuff like P – Program, A – Aperture Priority, Auto – Automatic, S – Shutter Priority (also known as speed – the shutter speed). There could be pictures of a Track star, Mountain Top, and a few other types of pictures. This is a picture of my camera dial on my Nikon D90. Let me begin by talking about the different modes from a high level and what they do.
I've been asked, "Dave, How did you learn photography?" or "Dave, How did you learn to take such great pictures?" It is such a difficult question to answer, because it isn't something you learn over night or even in a few days. To be honest with you, I learned photography by trial and error. I tried a lot of things and made a lot of errors. I even put the camera down and said "I quit!" Then I came back and tried some more and made some more errors. Then I started read books, watch YouTube Videos and read Blog posts from other photographers.
I'm trying to take photo's at least every other day and put a blog post on my website. On Easter Sunday, I set up the Studio Lights and a White Muslin background to take these Photo's. The Photo's with the Bright White background, actually used a Strobe light directly behind the subject. This will make the white background very white and bright. I have read that this helps give photo's that Glamor look that you see in Magazines. If you don't use a back lit background, then the White will start to look Gray. You will see that many of the other photos have this look.
So simple rule to remember, White Background + Strobe = White Background, White Background – Strobe = Gray Background. If you use a color Gel in front of the Strobe, then the white background will get this color.
Please enjoy these photos!


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One day I was mentally counting up how many lunches I packed for my daughter and when I got to over 1000 and had only estimated up to 6th grade – well I had to stop. What today?! Parents, workers and caregivers are always on the lookout for new ideas. We get it. And we've got some good ideas to share.
Tucking leftover grilled chicken or pan-fried tofu, fresh herbs and vegetables and/or beans into a tortilla or a spring roll wrapper make a quick and delicious alternative to sandwiches. I can show you how in this Full Circle video Fresh Avocado Spring Rolls.
There's a nice bunch of suggestions below in these three videos. For even MORE (like a bazillion more) checkout our friends at Laptop Lunches. Click to see their fall collection.
Below are three Cookus Interruptus favorites.
|Watch Jane pack Joaquin's lunchbox cleverly using leftovers from last night's dinner found in the refrigerator. Printable ideas and more links here.
|Holy last minute what's going in the lunchbox today? No problem. These are speedy to make, yummy going down. Printable recipe here.
|Because of the relatively inexpensive ingredients, this dish was popular during the Great Depression. We've made this redux a little quirky by using edamame. Printable recipe here.


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Spa & Wellness
Lovers of rest and wellness are at the right address at Palac Jugowice Luxury Spa. While you enjoy the fresh air and the woody surroundings, we pamper you in different ways. Discover our several offers of treatments and experience for yourself the positive effects. After a visit to the Spa & Wellness centre you will feel reborn.
Palac Jugowice Luxury Spa
Since July 2014 added to our assortment: A beautiful spa with saunas, two plunge baths, jacuzzi and a swimming pool. In short, the ideal place has a complete rest.
Beauty treatments
Let yourself be pampered in our wellness centre. Beauty treatments manicure or pedicure. At Palac Jugowice Luxury Spa you are at the right address.
Body treatments
Give yourself the space to come to complete rest. Our qualified staff gives you gladly a massage or other optional bodily treatments.


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A directory of services that consists of hotlines, medical therapy and assistance groups, therapy, caregiving, housing, child and parenting services, and public help. The much more you know about serving sizes, the more you will be able to support your self and your household consume a healthy amount of food. The simple act of talking to a buddy or loved more than the dinner table can play a huge role in relieving tension and boosting mood. Individual preference: I like to drag the chicken by way of the thickened marinade as I finish them up to add a yummy coating at the end prior to plating. Heh.) and I could use some a lot more organization, save more money, and stress less more than dinner. She has developed an entire variety of health foods to compliment healthy living and functionality.
Children (at times) get to have a say in what they eat, too, which tends to make the entire point a household activity rather than merely a parental chore. If you want to make your own from scratch, attempt ground chicken or turkey from your neighborhood grocery store or from Jennie or Butterball. Dinner time is a excellent time to speak to your children about any problems they may well be facing in their schooling and perform them out together. You'll save cash on the reduce of meat and stretch the meat for more meals when you make tasty casseroles, sauces, soups, stews, and stir-fries. The initial step to healthy consuming for youngsters is to have lots of great tasting, healthy food for them to consume at residence.
Very lean hamburger, or ground chicken and ground turkey: By obtaining 97% lean hamburger meat (or substitutes) and making use of whole wheat pasta and buns, we can cook American family favorites like hamburgers, or spaghetti as healthy household meals.
So we have meaty spaghetti sauce (on ricotta for me, noodles for them), chili, roast chicken with a starch for them, breakfast for dinner, and so forth. Healthy carbs are digested gradually, supplying long-lasting power and maintaining blood sugar and insulin levels steady.
Despite the fact that it takes more time, it is worth it to enable your youngsters to cook healthy meals with you. I have two tiny kids and loved so numerous of your ideas here, especially like my children by taking them purchasing and getting the prepare meals with me. I have pinned, voted and shared as well. Combining no cook and healthy is just a ideal tandem for me. These are intriguing possibilities that i can attempt.
When you reside alone it can be a challenge to consistently make healthy, economic, meals. We will stroll you through the morning and evening routines that will be the key to cooking healthy meals in below 30 minutes a day! I totally agree with the concept of enabling the little ones to decide on their personal healthy foods.


text: BAYTOWN, TX - There are many Christians and, not to mention the general public, who do not believe in giving in church or any place else. Many people get upset when they see the offering plate come around in church. Many believe that the pastor is pocketing all of the money and using it to … Continue reading I Don't Give Because The Church Is Corrupt


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Tomato Germination Using Energized Water
Wow! More great results – best so far – in our paper towel seed germination experiment series. This involved tomato seeds. A seed packet was divided in two, resulting in 133 seeds per group. The experiment ran for one week, […]Read More
Cilantro Seed Germination Success Story
We recently completed another germination experiment involving cilantro seeds. A single packet was divided in two, resulting in exactly 83 seeds for each "test plate." The germination experiment ran 5 days, from the 12th to the 19th of September, 2015. […]Read More
Chard Seed Germination Experiment
Plants love the "crystalline structured water" Hydreva produces. This is something we're now documenting via a series of paper towel based seed germination experiments. This article highlights one such experiment, which ran from Sept. 12-15, 2015. A packet of chard […]Read More
Energized Structured Water: A Better Approach
Back in the early 1900s, Austrian forest warden Viktor Schauberger (1885-1958) coined the term "living water" because his research discovered that water has a unique vitality and "livingness" in its natural state. One of his sayings was,"Understand Nature, then copy […]Read More
My Hydreva Test Garden
Whew! I seriously underestimated how much work would be involved in preparing my new Hydreva Test Garden. The issue is that the soil here is extremely rocky. I had to excavate down about 3′ just to level the plot then, […]Read More
Water Pressure & Water Magic
Hydreva's amazing water quality improvements rely on two primary factors: A precise and complex vortexing dynamic established within the inner chamber of the unit, which both raises the energetic state of the water (an "implosion effect") and erases negative patterns […]Read More
Water Frequencies & Health
Hydreva® technology involves the science of affecting water quality by using what scientists refer to as EMS (Electro-Magnetic Signals) to induce changes to the structure and energetic state of water molecules and molecular clusters. This involves frequencies in the ELF […]Read More
Electromagnetic Frequency and Water Geometry
A fundamental fact associated with Hydreva® technology is that specific electromagnetic frequencies not only impart to water a higher and healthier energetic state, but that specific frequencies also associate with specific geometries of water moleculer clusters. Both have great bearing […]Read More
Water's Mysteries and Secrets
Have you seen the 2005 BBC documentary, "Top Secret Water?" Top Secret Water is part of a fast-growing list of resources demonstrating that mainstream science missed the boat regarding some of water's most important characteristics. Victor Schauberger was on to […]Read More
The Evolution of Water Treatment
The History of Water To fully understand the chronicles of water treatment we have to look back at scientific history. In 1860, there was a scientific debate between Louis Pasteur's Germ Theory and Antoine Bechamp's Terrain Theory. Pasteur's Germ Theory […]Read More


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"How I Met Your Mother" had a strong, emotional sendoff as the series had its first-ever San Diego Comic-Con panel as it's gearing up for its ninth and final season. The full cast – Neil Patrick Harris, Cobie Smulders, Alyson Hannigan, Jason Segel and Josh Radnor — got an overwhelming welcome from fans who camped out to get a chance to see the CBS sitcom's actors.
"Thank you to everyone who waited in line," co-creator Craig Thomas tells the crowd. "We were all there among you, we were just dressed in Dothraki."
The panel began with a video teaser for the coming Season 9. It opened in the classic "How I Met Your Mother" manner, but Ted's future character was interrupted by his two children, who have grown up quite a bit over the past eight years (see the video below). They yelled at him for making them spend eight years on the couch so they could hear the story of how he met their mother, and finally future-Ted promised to finish the story. Unfortunately we have to on Sept. 23 for that journey to begin.
"This season is for you guys, this is our goodbye to you guys and our appreciation to you," co-creator Carter Bays says. "Decades will span over the course of this season within this one weekend."
Expect to see a lot of familiar faces reunite for Robin and Barney's wedding. Wayne Brady will be back. Plus Harris revealed that James is getting a divorce, which "puts things into a little bit of a pickle." Still, he says he wishes we'll see "BritBrit" again (Britney Spears, for those of you who aren't "HIMYM" fans).
"I really hope we get to meet Robin's mom," Smulders says. Harris adds with a wry look on his face, "I'm hoping the same thing."
Music was a hot topic during the panel. Smulders sang a bit of "Let's Go To The Mall," which can be watched below, while Segel sang his Dracula musical track and the whole cast sang the "Bang Bang" song. Still, they don't know if a musical number will be in Season 9, though there was a tease that Robin Sparkles could make a reappearance. "It's a wedding," Thomas says. "People sing songs at weddings." They dance as well, so expect another epic Barney and Robin dance session at the wedding.
It's also worth noting that there are still several slaps left to be given. "There is going to be an episode in the middle of the season that takes place during the course of one slap," Thomas says. "That's literally the framing device for an entire episode."
Of course, Season 9 is about getting to know the mother as well. She has finally been cast, and the creators made it very clear that fans will get to know Cristin Milioti's character.
"She's just really wonderful. I couldn't be happier," Bays says. Director Pam Fryman adds, "When you tune into the season premiere, you will not be disappointed."
The key point of the season will be that "How I Met Your Mother" will get to say goodbye to its fans. "I feel very lucky that we get to kind of say goodbye," Smulders says. Hannigan adds, "It is just so amazing that a sitcom could have fans like you guys."
For the record, the best line of the panel went to Harris. "I never thought I'd get to make out with so many chicks. A lot," he says. "I dry bumped an old lady for like more than hour — and then I came to work."
Here's the video of Ted's kids (Lyndsy Fonseca and David Henrie) chewing him out:


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Official Batman VS Superman Teaser Trailer
The official Batman VS Superman teaser trailer was released the other night; about a day after the leaked version hit the net. When I initially saw the leaked version, I theorized that it was a fake for various reasons (you can read about that here if you are so inclined). Obviously, the leaked version we saw… Read More »


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Meet local artisan Eliza Sears on Sunday, November 6, 3pm – 6pm
From summers beach-combing the rocky Maine shores to home excursions on the beaches of Maui, Eliza's Kamaile jewelry reflects a lifetime infatuation with serendipity and natural beauty. Eliza combines unusual and unique gemstones with new ways to twist, hammer and shape metals into striking pieces.
Her inspiration comes from the rugged Northern California coast, her magical two daughters and all the light and beauty her son shines through from the other side.


text: Highmount, N.Y. - Belleayre's summer season begins on Saturday, May 26 when the Belleayre Beach at Pine Hill Lake opens for weekends. The Belleayre Beach day use area offers facility amenities such as a white-sand swimming beach, kayak and paddle boat rentals, BBQ facilities and rentable pavilion space with electricity and grills for private parties, reunions and other gatherings. The facility will be open to the public full-time from June 16 through Labor Day. That is the fifth year that the Aqua School at Belleayre Beach will be selling aquatics programming for children and adults. Be sure to visit Belleayre's website for class and specialty workshop listings; call now to make reservations because registration is limited. Eco-Adventures are scheduled on weekends throughout the summer, offering local nature activities free of charge to all guests such as making walking sticks, informative talks about nature, the Junior Naturalist Program for Kids and more. Be sure to visit http://www.belleayre.com/ for programming details on activities to take place this summer at the Belleayre Beach.


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These beauties are for Anne Wheaton and those others that actually order tea with, "Tea, Earl Grey, hot," in the manner of a certain Captain, and just receive a blank stare. I don't ever order tea when I go out, but if I did, that is how I would do it. How sad that anyone might not get the reference.
Speaking of the above reference, did anyone else know besides the millions of people that follow certain other people on twitter (@wilw, @levarburton, @jonathansfrakes, @brentspiner) that the entire cast of Star Trek: The Next Generation just reunited at the Calgary Comic & Entertainment Expo held less than 3 weeks ago? Now, sure, it was a big theatre, but as a huge Next Generation fan, why the heck wasn't this thing televised or something? Of course you can pretty much watch the whole thing online here or here and OK lots of other places but it would've been awesome to have seen it live. I also really like this recap and this is pretty funny (make sure you scroll all the way down).
I showed a picture from the reunion to my oldest daughter (I think it was this) and she didn't know who the people were. *sigh* I think now is the time to begin to school her with episodes from Netflix. I remember watching the series with my mom, her favorite was The Offspring, and now I can do that with my daughter. I totally remember buying her that episode from our local Suncoast for a birthday or holiday or something (geez, I'm old).
So speaking of moms and tea, I think this cupcake would be really great for a Mother's Day Tea! If I had to do it over again, I would make the flavor just a bit milder by using plain milk or only putting one bag worth of tea leaves in the batter instead of two but really it is to your taste. While I was eating the batter (yes, eating the batter), having used the tea steeped milk and two bags worth of tea, I thought the batter was AWESOME but after baking, I think going just a bit milder may have been better.
Um, if you need another GeekyLink after the above post, I want to be your best friend.
Earl Grey Cupcakes with Lemon Scented Whipped Cream
barely adapted from Christine Wei
1/2 cup unsalted butter, softened
1 cup granulated sugar
2 eggs
1 1/2 all purpose flour
2 1/4 teaspoons baking powder
1 teaspoon salt
1/2 cup milk
2 bags of Earl Grey tea to steep in milk
2 bags of Earl Grey tea for the batter
Make your lemon sugar (see below) for the whipped cream.
Preheat your oven to 350°. Line 1 cupcake pan with liners.
In a small saucepan, heat your milk over low heat to just barely boiling and steep two bags of tea. Once the milk gets to barely boiling shut off the heat and continue to steep for five minutes. Stir occasionally during the five minutes to prevent filming. Set aside to cool completely. (If you want a milder flavor you can skip the steeping and just use plain milk.)
In the bowl of a stand mixer, place your butter and sugar and cream until light and fluffy. Add your eggs, one at a time, making sure the egg is fully incorporated after each addition.
If your tea leaves are finely ground, you won't need to do this but if not, place your tea leaves in a spice grinder until it becomes a fine powder. I just used Trader Joe's bagged Earl Grey and I did put it through my grinder but it would've been just fine if I didn't. Then in a small bowl, place the tea, flour, baking powder, and salt and whisk together.
Beat half of the dry mixture into the butter mixture until well blended. Add the milk, making sure it is cool, and the remaining dry mixture until just combined.
Fill your prepared cupcake pan evenly with batter. I used my ice cream scoop. Bake for 18-20 minutes. Cool completely
This is supposed to make 12 cupcakes but I came up with 13.
Lemon Scented Whipped Cream
1/4 cup granulated sugar
2 teaspoons lemon zest
2 cups whipping cream
In a small bowl, place your sugar and your lemon zest. Using the back of a metal spoon, crush the lemon zest into the sugar until the zest is well incorporated and the sugar is completely coated. Set aside for about an hour. If setting aside for longer, seal your mixture in an airtight container.
Place the lemon sugar and whipping cream into your mixing bowl and stir until well incorporated. Chill the mixture and your whisk or beaters for 3o minutes.
Whip your cream and sugar mixture until stiff peaks form. If you find some of the zest has accumulated on your beater, you can either scrape it off and leave it out or incorporate it back in for looks (the oils in the zest already got into your sugar so it doesn't need to be there unless you think it looks pretty).
Pipe whipped cream generously onto cupcakes and enjoy!


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Just a year after California voters approved a multi-billion dollar water bond, another may be on the way. Governor Jerry Brown's former top water official is pushing another initiative to upgrade the state's water system.
Jerry Meral, director of the Natural Heritage Institute's water program, says more is needed to ensure an adequate water supply.
"If the state wanted to, it could spend tens of billions of dollars, and probably should eventually, because this is a dry state. It's probably going to get drier because of climate change," Meral says. "We've got to do it one step at a time, and this would just be the next step."
Meral is most well-known for a controversial plan to build water tunnels under the Sacramento-San Joaquin Delta, but he is also one of the state's most influential environmentalists and an experienced author of initiatives.
A draft proposal Meral sent to environmental groups and state water officials does not contain a dollar figure, but Meral says it won't exceed $5 billion. The draft would distribute unspecified amounts to conservation, water reuse and recycling projects, desalination and existing infrastructure improvements.
Neither Brown nor any major environmental group has taken a position on the proposal.


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The 2006 employee benefits survey, released Friday, indicated that employees' satisfaction with benefits has increased overall since 2004, when the first such questionnaire was distributed.
The latest survey was administered to a random sample of 2,000 federal employees in August 2006, and sought to assess attitudes about the importance, adequacy, value and competitiveness of federal benefit programs. The target population included almost equal numbers of employees with three or more years of federal service and new hires who had less than three years of service. Of the 2,000 canvassed, 850 participated.
Respondents answered a 59-item questionnaire regarding the government's 10 benefit programs, including its 401(k)-style Thrift Savings Plan, employee health benefits, retiree health benefits, retirement annuities, life insurance, long-term care insurance and flexible spending accounts.
The portion of respondents who rated benefits as important increased by an average of 3 percentage points since 2004 across all programs. Those who said benefits are adequate increased by 4 percentage points; the portion grading benefits as valuable increased by 5 percentage points; and the group that said benefits are competitive with the private sector increased by 7 percentage points.
"This survey reinforces the importance of providing quality benefits to employees to ensure the federal government can continue to attract an effective civilian workforce," said OPM Director Linda Springer.
The TSP, employee health benefits, retiree health benefits and retirement annuities consistently received the highest ratings in importance and value. Additional programs that are not available to all employees -- telework, child care subsidies and health and wellness -- received lower ratings for importance and value.
"Just as OPM believed it was important to launch a new dental and vision benefits option last year to meet employees' needs, we are committed to continuing to search for ways to help the federal workforce better manage their overall health care, plan for their financial futures and assist in other areas," Springer said.
The benefits survey was similar to portions of OPM's federal workforce survey, designed to gauge employees' perceptions of their jobs and views on management challenges. That broader survey also measured employees' satisfaction with pay and benefit programs, and found the government's time-off policies among the best-liked.


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By integrating a novel patient-observer technology into a redesigned clinical workflow, the neuroscience unit at Mission Hospital (Asheville, North Carolina) achieved zero unassisted inpatient falls and zero injuries during a 3-month pilot period in 2015. Original neuroscience-unit fall rates during a 12-month baseline period from August 2014 to July 2015 were 5.74 total falls, 4.77 unassisted falls, and 0.91 injuries per 1,000 patient-days of care.
Key Takeaways
A busy neuroscience unit can successfully redesign its processes to adopt innovative fall-reduction technology.
Review your institution's multicomponent fall-prevention program and monthly falls data to identify opportunities for improvement.
Use a multidisciplinary team to come up with creative ways to reduce inpatient falls; involve that team in the implementation phase.
Ensure that technology solutions and redesigned clinical workflows complement each other.
Identify metrics of success, track them continuously, and analyze them at regular intervals.
The Challenge
Of the hundreds of thousands of patients who fall in U.S. hospitals each year, 30% to 50% are injured in the fall. Such falls frequently prolong or complicate hospital stays, adding 6.3 days to the typical stay in one study. A single patient fall with injury costs an average of nearly $14,000. A systemic review of the inpatient fall-prevention literature concluded that inpatient multicomponent programs reduce falls effectively, but with no clear evidence about which program components work best.
At Mission Health, we have long adhered to standard fall-prevention interventions: bed locked in low position with rails up; call light, call bell, assistive devices, and personal items within the patient's reach; nonslip patient footwear; clutter-free room; appropriate use of sensory aids; dry floor and adequate lighting; hourly clinician rounds; and patient and family education. We have also used the patient's individual fall risk to tailor interventions, such as bed and chair alarms, yellow identification armbands, and alert signage outside the patient's room. Despite our multicomponent fall-prevention program, compassionate care staff, and strong culture of safety, falls on the neuroscience unit still occurred at an overall rate of 5.74 per 1,000 patient-days of care. We believed this rate could be significantly reduced.
The Goal
Mission Health collaborated with Cerner Corporation to design, develop, and trial-test a scalable strategy for reducing falls on the hospital's 34-bed neuroscience unit. The approach, jointly funded by Mission Health and Cerner, emphasized new technology and redesigned workflows as an addition to the standard fall-prevention program. The goal was to conduct a 3-month pilot and evaluate the impact of a "virtual sitter" system (described below) as an alternative to using qualified staff sitters in patients' rooms. Impact was measured by comparing the two approaches in terms of fall rates, injury rates, and patient-to-sitter ratio. Both groups received the standard fall-prevention interventions listed above.
The Execution
"Virtual sitter" technology. In October 2014, Cerner Corporation first introduced the Mission Health Center for Innovation to Microsoft® Kinect® technology, which uses a depth sensor to visualize full-body 3-D movement within a 20-foot range. The system's infrared camera, acting as a virtual sitter, can monitor a patient's movements under any ambient light. Thanks to open-software programming, a unique application can be created to define and draw virtual zones, trip wires, and other trigger points around a patient within a field of view. A continuously live video feed is sent across a secure wireless network to a high-definition monitor. Additional features include two-way audio, voice recognition, patient-privacy modes, and customizable alerting. When clinical leaders and bedside staff were shown a demonstration with mock patients, the nursing unit manager for neurosciences immediately recognized that this system might reduce the fall rate for high-risk patients. He volunteered to be the clinical sponsor for a pilot project.
Nursing workflow. The neuroscience unit had the highest historical fall rate at Mission Hospital (excluding behavioral health units). Clinical leaders, supported by the neuroscience unit director and nursing manager, assembled a multidisciplinary project team focused on adopting the "virtual sitter" technology and redesigning processes to reduce fall rates. Almost all patients admitted to the neuroscience unit are at risk for falls, according to the Morse Fall Scale (MFS).
Given that we had only six "virtual sitter" cameras for the pilot, a team of registered nurses from the neuroscience unit used the MFS criteria and clinical expertise to develop an algorithm to assist nursing staff in identifying the highest-risk patients for participation in the pilot. If a patient met the algorithm's criteria for high risk, the nurse would educate that patient and/or family member about the virtual sitter system, enter a nursing order, and register the patient with the monitor technician (stationed at a central location on the unit). A wireless camera was placed on a wall mount and plugged into an electrical outlet in the patient's room. Within 1 minute, the monitor technician had a full view of the room, could introduce himself or herself via two-way audio, and then briefly explain the "virtual sitter" monitoring system to the patient and family. The algorithm's effectiveness in identifying patients at highest risk for falls has not been fully validated.
Technician workflow. A select few certified nursing assistants (CNAs), serving as monitor technicians, were trained on the system's software to ensure that monitored patients' rooms were properly configured. The monitor technician remotely draws virtual zones and virtual trip wires around the patient's bed or chair, and visual and auditory alerts are set to detect when a patient moves across the virtual boundaries (see video). First, a red box outlines the patient's video display window. Then an easily interpretable audible alert delivers the appropriate message, such as "patient is getting out of bed." The highly customizable, user-friendly interface ensures that the Kinect® sensor detects risky patient behaviors while minimizing alert fatigue.
Clinical pilot phase. After nursing-staff champions and monitor technicians on the neuroscience unit became comfortable with the new workflows and technology, a 3-month, six-camera "virtual sitter" pilot was launched in August 2015. The aforementioned algorithm identified patients at highest risk for falls, the ideal candidates for the new system. Patients at risk for suicide, homicide, drug overdose, or under legal restriction required an in-person (not a virtual) sitter, as per hospital policy. In all, 15% of patients in the neuroscience unit were enrolled in the 3-month pilot.
When a patient's movements generated a virtual sitter alert, the monitor technician intervened using the following escalation pathway:
- Use the two-way audio interface to interact with the patient. Either direct the patient to remain in the bed or chair, or assess the need for further intervention.
- Contact the patient's registered nurse or CNA depending on the patient's need.
- Contact the unit supervisor for emergency situations.
Monitor technicians used VoIP (Voice over Internet Protocol) phones to communicate with the care team when their involvement was required. Each technician intervention was recorded on a log sheet to track their number and effectiveness. The pilot project team met weekly to review outcomes and identify opportunities for improvement.
The Metrics
The 98 patients monitored with the virtual sitter (during 348 patient-days of care) experienced zero unassisted falls and zero injuries during the 3-month period from August through October 2015. All other patients on the neuroscience unit had an unassisted fall rate (per 1,000 patient-days of care) of 4.06 and an injury rate of 2.45 during the same period. Analysis showed that verbal redirection alone (accounting for 50% of all virtual sitter interventions during the pilot) was highly effective in keeping the patient in his or her bed or chair. This discovery was significant because the verbal redirection not only averted patient falls, but it also prevented nurses from being interrupted from other tasks.
By the end of the pilot, there were zero falls and zero injuries for the patients monitored with the "virtual sitter." These highly encouraging results prompted the hospital's leaders to support the continued use and expansion of the "virtual sitter" technology and redesigned workflows. Indeed, the 3-month pilot (in patients at highest fall risk) was allowed to continue after the formal pilot ended. The figure below compares rates of falls and injuries for the entire neuroscience unit during the 12 months before and after the "virtual sitter" program was instituted. Although only about 15% of patients were enrolled in the "virtual sitter" program during the second 12 months, the overall annual rate of falls and injuries for the unit declined significantly — in effect, an intervention for a small subset of patients was so powerful that it had a clear impact on the unit's overall performance.
Given that Mission Health's "virtual sitter" project is in its early stages (and not yet at full scale), we have estimated our expected financial returns. Before the virtual sitter pilot, the annual number of hours for non-mandatory bedside staff sitters (1 sitter per patient) was approximately 47,000 (cost, ~$680,000). Extrapolating from our experience with virtual sitters thus far, we expect to reduce annual bedside-sitter hours by 42% — to roughly 27,300 — during the next 2 years (a minimum savings of $286,230). If we grow the patient-to-virtual sitter ratio to 12:1, the average cost is expected to decline from $350 (using 1 in-room sitter for each patient) to $29 per patient per inpatient day (using virtual sitters). Given the estimated non-reimbursable cost of $14,000 per fall with significant injury, Mission Hospital has the potential to reduce its fall-related costs by more than $250,000.
Lessons Learned
The technology for motion detection and alerting functioned as designed and as expected during the pilot period. Nonetheless, we see opportunity for improvement.
For example, although monitor technicians successfully used VoIP phones to contact the care team, a faster, scalable, more reliable, less labor-intensive alternative is desirable. We will now explore using a platform that automatically communicates rapidly and reliably with the right care team member at the right time for the right intervention.
We also would like to develop capabilities that monitor patients in multiple units, on multiple floors, across multiple hospitals from a single location. The pilot used a 6:1 patient-to-monitor technician ratio, but the technology's alerting capabilities and our experience suggests that ratio can increase substantially, perhaps to 12:1.
Finally, we are exploring opportunities to use the virtual sitter system in other units at the hospital and, subsequently, across all Mission Health hospitals, with an eye toward its becoming a standard component of all fall-prevention programs. Potential additional uses include patient elopement, virtual visits, nurse documentation through voice recognition, and others.
Acknowledgments: We thank Josh Lewis, RN; Tony Guidone, RN; Ellen Blackmon, RN; Jessica Martin, RN; Noelle Shepherd, CNA; Stephanie Burnette, RN; Rhonda Robinson, MSN; Chad LaRowe; Michael Kusens; the entire Mission Neuroscience unit care team and clinical support staff; and Cerner.
This case study originally appeared in NEJM Catalyst on January 19, 2017.


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A cool and healthy option for our youth
The rink, scheduled to be 185 feet long and 85 feet wide, will be the only inline rink of its kind in the tri-county area. While much of the time it will be available for kids to skate free of charge, the possibilities are many as the parks and recreation department eyes leagues and tournaments for inline hockey.
An inline skating rink wasn't part of the city's recreation plan, but it should provide a nice boost to the city's offerings. And better yet, officials say building this rink may help the city secure grant money for other parks and recreation improvements. That certainly would be an added bonus for this new endeavor.
While some may bristle a bit at the idea of spending money to build an inline skate park, we think it's a positive and proactive move on the part of the city. The rink will cost just under $150,000 to construct, with $50,000 coming from parks and recreation and the remainder coming from a healthy city equipment fund. We've already mentioned the possibility the rink could lure grant dollars for further improvements, not to mention visitors. In the end, an inline skating rink ultimately offers our young people something "cool to do" that also passes the parent test. And that may be the very best benefit of all.


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Resources for KS2 Primary Schools in Reading and Düsseldorf
In 2017, to mark the 70th anniversary of the founding of the Reading Düsseldorf Association, we produced a 10 page education resource for primary schools (Key Stage 2 level). This is suitable for primary schools in both Düsseldorf and Reading.
To download the resources please click on the materials below:
Primary Activity pack (size 2656kB, PDF)
Primary Activity pack answer sheet (size 550kB Word)
Primary Activity pack (size 2496kB, PDF, Deutsche version)
Primary Activity Loesungen (size 526kB, Word, Deutsche version)
Activity packs are PDFs, answer sheets are locked Word documents.
To view PDFs you may need to download Adobe Reader (get.adobe.com/uk/reader/)