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Combination of different agents is widely used in clinic to combat complex diseases with improved therapy and reduced side effects. However, the identification of effective drug combinations remains a challenging task due to the huge number of possible combinations among candidate drugs that makes it impractical to screen putative combinations.
In this work, we construct a 'drug cocktail network' using all the known effective drug combinations extracted from the Drug Combination Database (DCDB), and propose a network-based approach to investigate drug combinations. Our results show that the agents in an effective combination tend to have more similar therapeutic effects and share more interaction partners. Based on our observations, we further develop a statistical approach termed as DCPred (
- Pred
The drug cocktail network constructed in this work provides useful insights into the underlying rules of effective drug combinations and offer important clues to accelerate the future discovery of new drug combinations.
Drug combination is the combination of different agents that can achieve better efficacy with less side effects compared to its single components. Recently, it is becoming a popular and promising strategy to new drug discovery, especially for treating complex diseases, e.g. cancer [1-3]. For example, Moduretic is the combination of Amiloride and Hydrochlorothiazide, which is an approved combination used to treat patients with hypertension [4,5]. Chan et al. identified a combination drug, namely Tri-Luma, for combating melasma (dark skin patches) of the face based on efficacy and safety experiments [6]. Agrawal et al. found two effective combinatorial drug regimens to treat Huntington disease based on prescreening in Drosophila [7]. In addition, through the synergistic antiangiogenic effects, very low-dose combinatorial use of vinblastine (VBL) and rapamycin (RAP) was demonstrated to inhibit the proliferation of the endothelial cells much more effectively than single drug treatment both in vitro and in vivo [8]. Recently, Lehar et al. found that synergistic drug combinations may have less side effects, because synergistic drug combinations are generally more selective to particular cellular contexts than single agents, and the dosage of each compound in combination will be reduced comparatively [9]. Despite of the extensive efforts that have been made to discover new drug combinations in the past few decades, the majority of effective combinatorial drugs used in clinic were discovered through experiences, which generally require labor-intensive and time-consuming "brute force" screening of all possible combinations among the approved individual drugs [10]. In a drug combination, a drug may promote or suppress the effect of another one. For instance, cyclosporine increases the effect of sirolimus, while bupropion decreases the effect of cyclosporine. As a result, two drugs may have a totally new effect that is different from the ones of either individual drugs [11,12]. Accordingly, the presence of potential drug-drug interactions (DDIs) and the possibility of pharmacokinetic interventions between the drugs could confound the identification of effective drug combinations [13]. Furthermore, the number of possible combinations will increase exponentially with the increasing availability of single drugs. For example, in the case of four drugs, there will be six possible combinations. This number would be enormous considering the fact that there are thousands of approved drugs. Due to the huge search space of possible combinations between known drugs, the identification of optimal and effective drug combinations is a non-trivial and challenging task.
Therefore, it is necessary to develop effective in silico methods that are capable of discovering new drug combinations prior to combination synthesis and practical test in the lab. Owing to the completion of human genome sequencing projects and the advancement of molecular medicine, extensive system biology efforts have been made to discover new combinations based on molecular interaction networks [14,15] in the past few years [16-19]. Nevertheless, there is still a long way to go before we reach the stage of devising generally applicable and effective prediction models. Recently, there have been considerable progresses in developing new approaches for identifying drug-drug interactions and even drug combinations [13]. In this context, Geva-Zatorsky et al. have recently found that the protein dynamics in response to drug combination can be accurately described by a linear superposition of the dynamics under the corresponding individual drugs [16]. Their study indicated that protein dynamics of three- and four-drug combinations can be predicted based on the drug combination pairs, thereby providing a useful way for reducing the search space of possible drug combinations. Calzolari et al. devised an efficient search algorithm originated from information theory for optimization of drug combinations based on the sequential decoding algorithms [17]. More recently, researchers have also developed computational frameworks for predicting drug combinations and synergistic effects based on high-throughput data [18-20].
In this work, we study the drug combinations in terms of their therapeutic similarity and the network topology of a drug cocktail network constructed from the effective drug combinations deposited in the Drug Combination Database (DCDB) [21]. We find that the drugs in an effective combination tend to have more similar therapeutic effects and share more interaction partners in the context of drug cocktail network. We further develop a statistical approach called DCPred to predict possible drug combinations and validate this approach based on a benchmark dataset with all the known effective drug combinations. As a result, DCPred achieves the overall best AUC (Area Under the receiver operating characteristic Curve) score of 0.92, demonstrating the predictive capability of the proposed approach and its potential value in identifying new possible drug combinations.
Results and discussion
The drug cocktail network
In this study, we extracted 239 known effective pairwise drug combinations from DCDB [21]. The information of ATC code for each drug was obtained from DrugBank [22]. Based on these datasets, we constructed a drug cocktail network with 215 nodes and 239 edges (see Figure 1 for the visualization of this network), where nodes represent the drugs and an edge is connected if two drugs are found in an effective drug combination. Building up this network can thus give the readers a visual impression of the relationships between drugs that can form effective combinations. Moreover, the network theory can be utilized to explore possible combinatorial mechanisms between drugs. In Figure 1, the size of each node approximates its degree, and the width of each edge approximates the therapeutic similarity (TS) (as defined in Equation 3) between the two drugs linked by the edge, while the grey edges indicate that the two drugs linked by the edge have totally different therapeutical effects. In addition, we found 102 drugs that have at least two neighbors in the drug cocktail network, which we termed as "star drugs" hereafter and 91 of which have target protein annotations in DrugBank.
Figure 1. The drug cocktail network. A node represents a drug and an edge denotes an effective combination consisting of the two drugs linked by the edge. The hub drugs that have more than 6 neighbors are colored in red. The size of each node approximates its degree, the width of each edge approximates the therapeutic similarity (see equation 3) between the two drugs linked by the edge, and a grey edge means that the two drugs linked by that edge have completely different therapeutic effects. The numbers in panel 1-6 represent the top six largest child networks from the drug cocktail network.
Since most of biological networks are scale-free networks [23], we analyzed the topology of the drug cocktail network in order to find out whether it is also a scale-free network. The degree distribution of the drug cocktail network is shown in Figure 2. It is evident that the degree distribution follows a power law distribution, suggesting that it is indeed a scale-free network. That is, the fraction P(x) of nodes in the drug cocktail network having x connections to other nodes can be described as:
Figure 2. The degree distribution of the drug cocktail network. The x-axis represents the common logarithm of the value of degree k, while the y-axis represents the common logarithm of the fraction of drugs that have the degree of k.
where c = 2.1 and α = 1.9 in this case.
As the drug cocktail network shown in Figure 1 is not fully connected, the top 6 largest subnetworks were chosen for further analysis. We considered the drug cocktail network as the union of these 6 subnetworks hereafter unless stated specifically. In particular, each subnetwork was found to be enriched for one or several therapeutic classes according to the ATC classification system, as shown in Table 1. In other words, the drugs having similar therapeutic effects tend to be clustered together in the drug cocktail network.
Table 1. The enriched ATC codes for child networks
To test our hypothesis that the drugs in one combination tend to have similar therapeutic effects, the drug cocktail network was compared against random combination networks. For this purpose, a therapeutic similarity (TS) score was calculated for each drug pair, and the average of all TS scores was used as the TS score for the whole drug cocktail network. The random combination networks were generated by randomly shuffling the edges while still preserving the degree for each node [24] in the drug cocktail network. This procedure was repeated for 1,000 times. To examine the statistical significance of the difference between the drug cocktail network and random combination networks, one P-value was calculated as the ratio that the TSs of random combination networks are larger than that of the drug cocktail network during the 1000 randomizations. The results are shown in Table 2 at different ATC code levels ranging from 1 to 4. The calculated P-values of the drug cocktail network across ATC code levels 1-4 are all equal to 0, strongly suggesting that the real drug combinations significantly differ from the random combination networks. Note that the 5th ATC code level was not considered here, as there is only one drug combination having identical ATC codes for all the five levels in the drug cocktail network. This means that the 5th ATC code level is not suitable for performing statistical analysis and thus it is not included in the analysis.
Table 2. The comparisons between drug cocktail network and random networks
Furthermore, we studied the therapeutic effects for the "star drugs" and their neighbors in the drug cocktail network in order to reveal whether the star drugs have therapeutic similarities to all their neighbors. Figure 3 shows the distribution of the TS scores for star drugs and their neighbors. For the effective combination pairs involving star drugs, 82% have therapeutic similarity, and most of the star drugs have similar therapeutic effects as the majority of their neighbors. In contrast, 78% of the combination pairs in the random network do not have any therapeutic similarity. These results suggest that one star drug tends to be used in combination with drugs that have similar therapeutic effects as the star drug.
Figure 3. The distribution of the TS scores between star drugs and their neighbors. Blue and red lines represent the drug cocktail network and random network, respectively.
Moreover, we also investigated the distribution of neighbor drug pairs of star drugs (Figure 4A and 4B), attempting to answer whether or not the drug pairs that share a star drug have therapeutic similarity. To address this, we divided the neighbor drug pairs of a star drug into two groups, according to whether they have similar ATC codes, or whether they are approved effective combinations. We then calculated the percentage of effective combinations among drug pairs that share a star drug and have a TS score equal to or larger than a certain threshold (Figure 4C). From Figure 4C, we can see that the more similar therapeutic effects (as reflected by the TS score) two drugs have, the more likely they are effective combinations. Another important observation is that the combinations between drugs sharing similar therapeutic effects and star drugs are more likely effective combinations.
Figure 4. Star drugs and their neighbors. (A) The distribution of neighbor drug pairs of star drugs. The neighbor pairs of star drugs can be classified into two groups, according to whether they have similar ATC codes, or whether they are used as effective combinations. (B) Schematic view of the relationship between two neighbors d1 and d2 of a star drug. (C) The percentage of effective combinations within neighbor drug pairs with TS equal to or larger than a certain threshold. Blue and red lines represent the drug cocktail network and the average of 1000 randomly generated combination networks, respectively.
In various networks, the hub nodes are generally considered to play important roles [25]. Therefore, we next studied the 14 hub drugs in the drug cocktail network, all of which have more than 6 neighbor drugs. The largest two hub drugs are DB00999 (Hydrochlorothiazide) and DB00072 (Trastuzumab). Hydrochlorothiazide is used to treat high blood pressure and edema [26,27]. According to the annotations in DrugBank and DCDB, we found that all the 18 drug neighbors of hydrochlorothiazide can be used to cure hypertension while all the drug combinations involving hydrochlorothiazide have been used to treat hypertension. Among these 18 combinations, 11 combinatorial drugs target different but related pathways while the other 7 ones target unrelated pathways (Additional file 1). In the case of Trastuzumab used to treat HER2-positive metatsatic breast cancer [28,29], 5 of its 10 neighbor drugs are used to treat breast cancer, while the other 5 have pesticide effects on neoplasm or other cancers. All the 10 drug combinations are used to treat breast cancer except the one used for treating gastric cancer. Additionally, 8 drug combinations target related pathways, while the other two target different unrelated pathways or cross-talking pathways (Additional file 2). Finally, these results, together with the consistent findings shown in Figure 3, strongly indicate that star drugs tend to have similar therapeutic characteristics as their neighbors.
Additional file 1. The annotation of the neighbor drugs of DB00999 (Hydrochlorothiazide).
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Additional file 2. The annotation of the neighbor drugs of DB00072 (Trastuzumab).
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In addition, we investigated the proteins targeted by the 13 hub drugs in the drug cocktail network that have target information. By mapping all proteins targeted by the drugs in the drug cocktail network to the human protein-protein interaction network retrieved from STRING database [30], we found that, in terms of the shortest distance between target proteins, hub drugs tend to have a closer relationship with their combination partners than the drugs having similar ATC codes (see Figure 5A). Furthermore, we analyzed the cellular localizations of these target proteins of the 13 hub drugs(see Figure 5B). More than 70% of the target proteins of the hub drugs are membrane proteins, which is reasonable considering that membrane proteins are widely involved in various biological processes and represent the largest class of drug targets.
Figure 5. Target proteins of hub drugs. (A) The blue line represents the shortest distances between the targets of hub drugs and the targets of their combination partners, while the red line represents the shortest distances between the targets of hub drugs and the targets of drugs that are therapeutically similar to hub drugs. (B) The distribution of cellular localizations of the target proteins of hub drugs.
Implication of drug cocktail network for possible drug combinations
As shown in Figure 3, 82% of the combinations between star drugs and their neighbors have therapeutic similarity, and most of the star drugs have therapeutic similarity to the majority of their neighbors in the drug cocktail network. Additionally, most of the effective combinations are observed to be located in the vicinity of drug pairs with similar ATC codes. Hence, it is possible to predict drug combinations from the set of drug pairs with similar ATC codes. Nonetheless, we found that there are only 74 known effective combinations in all of the 1181 possible combinations with similar ATC codes. Since the number of effective drug combinations is considerably smaller than that of random combinations between drugs having similar ATC codes, it is a challenging but crucial task to discover the effective combinations from the pool with a vast number of random combinations.
In Figure 4B and 4C, we can see that if two drugs with similar ATC codes have a common neighbor in the drug cocktail network, they are more likely to be combined together. Therefore, we assume that the two drugs having similar ATC codes and sharing a significantly larger number of common partners in the drug cocktail network are more likely to be combined effectively. Based on this assumption, we further developed a new statistical approach called DCPred to test this hypothesis and applied it to predict and rank all the possible drug combinations (See Materials and methods for more details). In particular, three different versions of DCPred were considered in this work, including DCPred1 considering TS only, DCPred2 considering TS and drugs with at least 2 neighbors, and DCPred3 considering TS and drugs with at least 3 neighbors. In the case of DCPred2 and DCPred3, all possible drug combinations were ranked in ascending order according to the p-value by equation (4), and the top ones were considered as putative effective drug combinations. While in the case of DCPred1, all possible drug combinations were ranked in descending order according to the TS value by equation (3), and the top ones were considered as putative effective drug combinations. The ranking list of drug combinations can be found in the additional files (Additional file 3 and 4). We found that two drugs with more common neighbors generally have higher rankings. Using the set of 74 effective combinations as the gold standard while the 1107 random ones as negative set (Additional file 3), we evaluated our approach in identifying new drug combinations. Figure 6 shows the ROC curves [31] obtained by different methods, where the drug pairs ranked above a given threshold were predicted as effective drug combinations (positives), while the rest were regarded as negatives. We then calculated the area under the ROC curves (AUC) [32] for these different DCPred models. As a result, DCPred2 achieved an AUC score of 0.88 (the green curve in Figure 6), in comparison with the AUC of 0.75 for the TS-based method (DCPred1) (the red curve in Figure 6). To comprehensively evaluate the predictive power of the three models, we also calculated three other performance indexes: Sensitivity, Specificity and Accuracy at varying thresholds for DCPred1, DCPred2 and DCPred3 models (See the Additional file 5, 6 and 7, respectively).
Additional file 3. The ranking of 1181 possible combinations by the DCPred2 model.
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Additional file 4. The ranking of 419 possible combinations by the DCPred3 model.
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Figure 6. The ROC curves of different DCPred models. DCPred1 uses TS only, DCPred2 uses TS and drugs with at least 2 neighbors, while DCPred3 uses TS and drugs with at least 3 neighbors, respectively.
Additional file 5. Prediction performance of the DCPred1 model at varying thresholds, as measured by Sensitivity, Specificity and Accuracy.
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Additional file 6. Prediction performance of the DCPred2 model at varying thresholds, as measured by Sensitivity, Specificity and Accuracy.
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Additional file 7. Prediction performance of the DCPred3 model at varying thresholds, as measured by Sensitivity, Specificity and Accuracy.
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Of the top 35 ranked drug combinations inferred by our models, 63% of them (22/35) are known effective drug combinations according to DCDB, and 37% (13/35) do not have any annotations in DCDB (Table 3). Nevertheless, 4 out of these 13 drug combinations were reported in the literature, i.e. the 13th, 22th, 34th and 35th in the ranking list (Table 3). The 34th ranked one is a combination of irinotecan and capecitabine, known as XELIRI, and used to treat metastatic colorectal cancer [33]. Alfonso et al. demonstrated that XELIRI is effective and safe as the first-line chemotherapy for treating advanced colorectal cancer or metastatic colorectal cancer [34]. The 13th ranked one is the combination of docetaxel and gemcitabine, the former interferes with the normal function of microtubule growth and destroys the cell's ability to use its cytoskeleton in a flexible manner, while the latter inhibits thymidylate synthetase leading to inhibition of DNA synthesis and cell death [35,36]. Levy et al. found that gemcitabine-docetaxel combination has a favorable risk-benefit profile and is an important new treatment option for women with metastatic breast cancer [37]. The 22th one is the combination of sorafenib and bevacizumab. The former interacts with multiple intracellular (CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT-3, VEGFR-2, VEGFR-3, and PDGFR-ß) to reduce blood flow to the tumor for the treatment of patients with advanced renal cell carcinoma [38], while the latter binds VEGF and prevents the interaction of VEGF to its receptors (Flt-1 and KDR) on the surface of endothelial cells [39]. Consequently, this prevents blood vessel proliferation and tumor metastasis for metastatic colorectal cancer and HER2-negative metastatic breast cancer. Azad et al. demonstrated that complementary inhibition of VEGF signaling has synergistic therapeutic effects, and this combination therapy has promising clinical activity over ovarian cancer [40]. The 35th one is the combination of thalidomide and lenalidomide. Thalidomide has been successfully introduced to treat multiple myeloma and its analogue, lenalidomide, is also effective in relapsed refractory myeloma [41]. The Thalidomide-lenalidomide combination can induce tumour cell apoptosis directly or indirectly by altering bone marrow microenvironment, and can be used in combination to treat multiple myeloma [42]. Both drugs bind to a common target PTGS2, which may play a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity [43]. Thalidomide and lenalidomide have been shown to significantly improve the overall and disease-free survival. Combination of these two drugs has recently emerged as a promising combination strategy to improve the patient outcome and drug toxicity, especially in the treatment of multiple myeloma (MM) and hematologic cancers [44].
Table 3. The novel predictions of DCPred2
If we only considered the combinations whose drug components have at least 3 neighbors, termed as DCPred3 (the blue curve in Figure 6), we predicted 40 combinations and 379 negative ones (Additional file 4). DCPred3 achieves an AUC score of 0.92. Compared with the aforementioned two models DCPred1 and DCPred2, based on the information of at least 3 neighor drugs, DCPred3 leads to the overall best performance. In this work, we considered the results by DCPred2 as the final results because only few drugs have more than two neighbors in the drug cocktail network. We hope that the DCPred models developed in this study can be used to facilitate the in silico identification of effective drug combinations and speed up the future discovery process.
Drug combination is a promising strategy for combating complex disease, but our complete understanding of the underlying mechanisms of drug combination is largely lacking at present. It is therefore imperative to develop efficient computational methods to infer effective drug combinations in order to reduce the labor-intensive, time consuming trial-and-error experiments. In this article, we extracted all the known effective drug combinations from DCDB and constructed a drug cocktail network, which includes 215 drugs and 239 effective drug combinations. Based on this cocktail network, we observed that the star drugs tend to have therapeutic similarity with their drug neighbors, and two drugs having similar therapy and sharing neighbors tend to be employed in drug combination. Our analysis also revealed that: 1) hub drugs usually have similar and even the same therapeutic effects as their neighbors; 2) target proteins of the hub drugs are often membrane or membrane-associated proteins; 3) the components in effective drug combinations usually have more similar therapeutic effects, making the drug cocktail network significantly different from the random combination networks.
From the above observations, we consequently developed a new statistical approach to infer and rank possible effective drug combinations by taking into account drugs with at least two or three drug neighbors. As a result, our DCPred2 and DCPred3 models achieved the AUC scores of 0.88 and 0.92, respectively, demonstrating a good performance. We further applied these models to rank all the possible drug combinations and found that the top ranked combinations are more likely to be effective combinations, according to the cross-reference to the literature or the similarity of their ATC codes. In particular, four combinations in the top 35 rankings have been verified as effective combinations by the literature search. We also show that there is a better chance for another 3 combinations to be effective combinations in terms of the pharmacological similarity. Our results in this study provide useful insights into the underlying mechanisms of effective drug combinations and hence important clues for efficiently reducing the search space of possible combinations within the approved drugs. Our approach may be further useful for developing more accurate models. The DCPred models are anticipated to be applied to screen more effective drug combinations with clinical importance.
Furthermore, the concentration of each drug in a combination is a crucial factor in the study of drug combination. However, it is currently difficult to utilize the dosage information of drugs without the knowledge of their quantitative dose-response profiles (e.g. drug induced gene/protein expression data) under different drug concentrations, due to the limited availability of such data. We will investigate drug combinations from this perspective in the future, when more data regarding drug concentrations become available.
Data sources
The annotations of drug combinations were retrieved from a newly released Drug Combination Database (DCDB) [21]. This is a major resource for collecting effective drug combinations from the literature. The target protein information, the Anatomical Therapeutic Chemical (ATC) code annotation of the drugs and protein subcellular localizations, were extracted from DrugBank [22]. Drug combinations that do not have ATC codes for the corresponding drug components and combinations with none or unclear efficacy were discarded. Finally, 194 effective drug combinations were obtained, including 76 approved combinations, 64 clinical combinations and 54 preclinical combinations. We then split the combinations with more than two drug components into combination pairs, resulting in 239 drug combination pairs. These drug combinations were used to construct a drug cocktail network (Figure 1), where the nodes represent drugs and the edges represent combinations, respectively. In the drug cocktail network, the size of each node denotes its degree and the width of each edge denotes the therapeutic similarity (TS) between the two drugs linked by the edge. The gray edge means that there is no therapeutic similarity between the two drugs.
Human protein-protein interactions (PPIs) with high confidence from STRING [30] were used to annotate this drug cocktail network, which includes 169,603 interactions between 11,289 proteins after removing pairs with low scores ( < 700).
Drug therapeutic similarity
The Anatomical Therapeutic Chemical (ATC) Classification System, which includes 5 different hierarchical levels, was used to classify drugs into different groups according to the organ they acted on and the therapeutic chemical characteristics. The k-th level drug therapeutic similarity (Sk) between two drugs is defined using the ATC codes of these two drugs:
where ATCk(d) denotes all the ATC codes at the k-th level of drug d. Note that a drug has five levels of ATC codes. A score, TS, is used to define the therapeutic similarity between two drugs:
where n ranges from 1 to 5. In this study, n = 3 is adopted considering that only a few drugs have the same ATC codes at the 5th level.
Drug combination prediction
We assume that two drugs are more likely to be combined if they share a large number of common drugs in the drug cocktail network. For example, if two drugs d1 and d2 with respective n1 and n2 partners have m in common in the drug cocktail network, there will be three groups in the neighborhood of the two drugs, i.e. (1) m drugs that are the neighbors of both drug d1 and d2; (2) n1 - m partners that are the neighbors of drug d1 only; and (3) n2 - m partners are the neighbors of drug d2 only [45]. Suppose that there are totally N drugs in the drug combination network, then a p-value between d1 and d2 can be calculated using the following equation:
If two drugs share more common drugs compared with all of their neighbors, the p-value computed by equation (4) will be closer to 0, which means they are more likely to be combined. We use the equation (4) to compute the p-values for all possible combinations and then rank the values in ascending order. As drug pairs with lower p-values are more likely to be combined, the prediction of effective drug combinations can be made given a certain p-value threshold. We term this framework that explores the drug cocktail network and predicts possible drug combination as DCPred (Drug Combination Predictor) and assess its performance for inferring effective drug combinations based on the curated drug combinations dataset.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
KJX implemented the computational method, carried out data analysis, and drafted the manuscript under the direction of XMZ and JS. JS and XMZ guided and coordinated the project, and improved the presentation of the manuscript by copy-editing and fixing language issues. All authors read, revised and approved the final manuscript.
XMZ was partly supported by the Innovation Program of Shanghai Municipal Education Commission (10YZ01), Shanghai Rising-Star Program (10QA1402700), and National Natural Science Foundation of China (61103075, 91130032). JS was supported by the National Health and Medical Research Council of Australia (NHMRC) Peter Doherty Fellowship and the Hundred Talents Program of the Chinese Academy of Sciences (CAS). KJX was supported by the Innovation Program of Shanghai University (SHUCX112015).
This article has been published as part of BMC Systems Biology Volume 6 Supplement 1, 2012: Selected articles from The 5th IEEE International Conference on Systems Biology (ISB 2011). The full contents of the supplement are available online at http://www.biomedcentral.com/bmcsystbiol/supplements/6/S1.
Argiris A, Wang CX, Whalen SG, DiGiovanna MP: Synergistic interactions between tamoxifen and trastuzumab (Herceptin).
Clinical Cancer Research 2004, 10:1409-1420. PubMed Abstract | Publisher Full Text
Osborne CK, Schiff R: Growth factor receptor cross-talk with estrogen receptor as a mechanism for tamoxifen resistance in breast cancer.
Breast 2003, 12:362-367. PubMed Abstract | Publisher Full Text
Marsh JC, Bertino JR, Katz KH, Davis CA, Durivage HJ, Rome LS, Richards F, Capizzi RL, Farber LR, Pasquale DN, et al.: The influence of drug interval on the effect of methotrexate and fluorouracil in the treatment of advanced colorectal cancer.
J Clin Oncol 1991, 9:371-380. PubMed Abstract | Publisher Full Text
Wilson DR, Honrath U, Sonnenberg H: Interaction of amiloride and hydrochlorothiazide with atrial natriuretic factor in the medullary collecting duct.
Can J Physiol Pharmacol 1988, 66:648-654. PubMed Abstract | Publisher Full Text
Frank J: Managing hypertension using combination therapy.
American Family Physician 2008, 77:1279-1286. PubMed Abstract | Publisher Full Text
Chan R, Park KC, Lee MH, Lee ES, Chang SE, Leow YH, Tay YK, Legarda-Montinola F, Tsai RY, Tsai TH, et al.: A randomized controlled trial of the efficacy and safety of a fixed triple combination (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) compared with hydroquinone 4% cream in Asian patients with moderate to severe melasma.
Br J Dermatol 2008, 159:697-703. PubMed Abstract | Publisher Full Text
Agrawal N, Pallos J, Slepko N, Apostol BL, Bodai L, Chang LW, Chiang AS, Thompson LM, Marsh JL: Identification of combinatorial drug regimens for treatment of Huntington's disease using Drosophila.
Proceedings of the National Academy of Sciences of the United States of America 2005, 102:3777-3781. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Campostrini N, Marimpietri D, Totolo A, Mancone C, Fimia GM, Ponzoni M, Righetti PG: Proteomic analysis of anti-angiogenic effects by a combined treatment with vinblastine and rapamycin in an endothelial cell line.
Proteomics 2006, 6:4420-4431. PubMed Abstract | Publisher Full Text
Lehar J, Krueger AS, Avery W, Heilbut AM, Johansen LM, Price ER, Rickles RJ, Short GF, Staunton JE, Jin X, et al.: Synergistic drug combinations tend to improve therapeutically relevant selectivity.
Nature Biotechnology 2009, 27:659-666. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Zimmermann GR, Lehar J, Keith CT: Multi-target therapeutics: when the whole is greater than the sum of the parts.
Drug Discovery Today 2007, 12:34-42. PubMed Abstract | Publisher Full Text
Pennati M, Campbell AJ, Curto M, Binda M, Cheng YZ, Wang LZ, Curtin N, Golding BT, Griffin RJ, Hardcastle IR, et al.: Potentiation of paclitaxel-induced apoptosis by the novel cyclin-dependent kinase inhibitor NU6140: a possible role for survivin down-regulation.
Molecular Cancer Therapeutics 2005, 4:1328-1337. PubMed Abstract | Publisher Full Text
Lewis BR, Aoun SL, Bernstein GA, Crow SJ: Pharmacokinetic interactions between cyclosporine and bupropion or methylphenidate.
Journal of Child and Adolescent Psychopharmacology 2001, 11:193-198. PubMed Abstract | Publisher Full Text
Tari L, Anwar S, Liang S, Cai J, Baral C: Discovering drug-drug interactions: a text-mining and reasoning approach based on properties of drug metabolism.
Bioinformatics 2010, 26:i547-553. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Zhao XM, Wang RS, Chen L, Aihara K: Uncovering signal transduction networks from high-throughput data by integer linear programming.
Nucleic Acids Res 2008, 36:e48. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Zhao XM, Wang RS, Chen L, Aihara K: Automatic modeling of signaling pathways by network flow model.
J Bioinform Comput Biol 2009, 7:309-322. PubMed Abstract | Publisher Full Text
Geva-Zatorsky N, Dekel E, Cohen AA, Danon T, Cohen L, Alon U: Protein Dynamics in Drug Combinations: a Linear Superposition of Individual-Drug Responses.
Cell 2010, 140:643-651. PubMed Abstract | Publisher Full Text
Calzolari D, Bruschi S, Coquin L, Schofield J, Feala JD, Reed JC, McCulloch AD, Paternostro G: Search Algorithms as a Framework for the Optimization of Drug Combinations.
Plos Computational Biology 2008, 4:e1000249. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Jin G, Zhao H, Zhou X, Wong ST: An enhanced Petri-net model to predict synergistic effects of pairwise drug combinations from gene microarray data.
Bioinformatics 2011, 27:i310-i316. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Wu Z, Zhao XM, Chen L: A systems biology approach to identify effective cocktail drugs.
BMC Syst Biol 2010, 4(Suppl 2):S7. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
Zhao XM, Iskar M, Zeller G, Kuhn M, Noort V, Bork P: Prediction of drug combinations by integrating molecular and pharmacological data.
Plos Computational Biology 2011, 7:e1002323. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Liu YB, Hu B, Fu CX, Chen X: DCDB: Drug combination database.
Bioinformatics 2010, 26:587-588. PubMed Abstract | Publisher Full Text
Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets.
Nucleic Acids Research 2008, 36:D901-D906. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Newman MEJ: The structure and function of complex networks.
Siam Review 2003, 45:167-256. Publisher Full Text
Maslov S, Sneppen K: Specificity and stability in topology of protein networks.
Science 2002, 296:910-913. PubMed Abstract | Publisher Full Text
Barabasi AL, Oltvai ZN: Network biology: understanding the cell's functional organization.
Nature Reviews Genetics 2004, 5:101-113. PubMed Abstract | Publisher Full Text
MacKay JH, Arcuri KE, Goldberg AI, Snapinn SM, Sweet CS: Losartan and low-dose hydrochlorothiazide in patients with essential hypertension - A double-blind, placebo-controlled trial of concomitant administration compared with individual components.
Archives of Internal Medicine 1996, 156:278-285. PubMed Abstract | Publisher Full Text
Salmela PI, Juustila H, Kinnunen O, Koistinen P: Comparison of low doses of hydrochlorothiazide plus amiloride and hydrochlorothiazide alone in hypertension in elderly patients.
Ann Clin Res 1986, 18:88-92. PubMed Abstract
Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, et al.: Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer.
New England Journal of Medicine 2005, 353:1673-1684. PubMed Abstract | Publisher Full Text
Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, et al.: Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.
New England Journal of Medicine 2005, 353:1659-1672. PubMed Abstract | Publisher Full Text
Jensen LJ, Kuhn M, Stark M, Chaffron S, Creevey C, Muller J, Doerks T, Julien P, Roth A, Simonovic M, et al.: STRING 8-a global view on proteins and their functional interactions in 630 organisms.
Nucleic Acids Research 2009, 37:D412-D416. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Hand D: Measuring classifier performance: a coherent alternative to the area under the ROC curve.
Machine Learning 2009, 77:103-123. Publisher Full Text
Fawcett T: An introduction to ROC analysis.
Pattern Recognition Letters 2006, 27:861-874. Publisher Full Text
Delord JP, Pierga JY, Dieras V, Bertheault-Cvitkovic F, Turpin FL, Lokiec F, Lochon I, Chatelut E, Canal P, Guimbaud R, et al.: A phase I clinical and pharmacokinetic study of capecitabine (Xeloda[reg]) and irinotecan combination therapy (XELIRI) in patients with metastatic gastrointestinal tumours.
Br J Cancer 2005, 92:820-826. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Garcia-Alfonso P, Munoz-Martin A, Mendez-Urena M, Quiben-Pereira R, Gonzalez-Flores E, Perez-Manga G: Capecitabine in combination with irinotecan (XELIRI), administered as a 2-weekly schedule, as first-line chemotherapy for patients with metastatic colorectal cancer: a phase II study of the Spanish GOTI group.
Br J Cancer 2009, 101:1039-1043. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Dent S, Messersmith H, Trudeau M: Gemcitabine in the management of metastatic breast cancer: a systematic review.
Breast Cancer Research and Treatment 2008, 108:319-331. PubMed Abstract | Publisher Full Text
Chang J, Makris A, Gutierrez M, Hilsenbeck S, Hackett J, Jeong J, Liu M-L, Baker J, Clark-Langone K, Baehner F, et al.: Gene expression patterns in formalin-fixed, paraffin-embedded core biopsies predict docetaxel chemosensitivity in breast cancer patients.
Breast Cancer Research and Treatment 2008, 108:233-240. PubMed Abstract | Publisher Full Text
Levy C, Fumoleau P: Gemcitabine plus docetaxel: a new treatment option for anthracycline pretreated metastatic breast cancer patients?
Cancer Treatment Reviews 2005, 31:S17-S22. PubMed Abstract | Publisher Full Text
Wilhelm SM, Adnane L, Newell P, Villanueva A, Llovet JM, Lynch M: Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.
Molecular Cancer Therapeutics 2008, 7:3129-3140. PubMed Abstract | Publisher Full Text
Los M, Roodhart JML, Voest EE: Target practice: Lessons from phase III trials with bevacizumab and vatalanib in the treatment of advanced colorectal cancer.
Oncologist 2007, 12:443-450. PubMed Abstract | Publisher Full Text
Azad NS, Posadas EM, Kwitkowski VE, Steinberg SM, Jain L, Annunziata CM, Minasian L, Sarosy G, Kotz HL, Premkumar A, et al.: Combination targeted therapy with sorafenib and bevacizumab results in enhanced toxicity and antitumor activity.
Journal of Clinical Oncology 2008, 26:3709-3714. PubMed Abstract | Publisher Full Text
Kumar S, Rajkumar SV: Thalidomide and lenalidomide in the treatment of multiple myeloma.
European Journal of Cancer 2006, 42:1612-1622. PubMed Abstract | Publisher Full Text
Anderson KC: Lenalidomide and thalidomide: Mechanisms of action - Similarities and differences.
Seminars in Hematology 2005, 42:S3-S8. PubMed Abstract | Publisher Full Text
Horrobin DF: A low toxicity maintenance regime, using eicosapentaenoic acid and readily available drugs, for mantle cell lymphoma and other malignancies with excess cyclin D1 levels.
Medical Hypotheses 2003, 60:615-623. PubMed Abstract | Publisher Full Text
Vallet S, Palumbo A, Raje N, Boccadoro M, Anderson KC: Thalidomide and lenalidomide: Mechanism-based potential drug combinations.
Leuk Lymphoma 2008, 49:1238-1245. PubMed Abstract | Publisher Full Text
Samanta MP, Liang S: Predicting protein functions from redundancies in large-scale protein interaction networks.
Proceedings of the National Academy of Sciences of the United States of America 2003, 100:12579-12583. PubMed Abstract | Publisher Full Text | PubMed Central Full Text


text:
|Design, purification and characterization of a soluble variant of the integral membrane protein MotB for structural studies.
MedLine Citation:
|PMID: 23193105 Owner: NLM Status: MEDLINE
|The bacterial flagellar motor is an intricate nanomachine powered by a transmembrane electrochemical gradient. Rotation is driven by the cumulative action of several peptidoglycan-anchored stator complexes on the rotor. In proton-motive force-driven motors, the stator complex is composed of a motility protein B (MotB) dimer surrounded by four copies of MotA, where both MotA and MotB are integral membrane proteins. The lack of full-length MotA and MotB structures hinders understanding of the mechanism of torque generation. Given the low levels of expression and low stability of detergent-solubilized MotB, a soluble chimaeric variant was engineered, where the two transmembrane helices of the MotB dimer were replaced by a leucine zipper. The biochemical and biophysical analysis of the resultant protein showed that it was properly folded, stable, behaved as a monodisperse dimer at low pH, had molecular dimensions close to those expected for native MotB and yielded reproducible crystals. The chimaeric protein is, therefore, a good candidate for structural studies. This 'solubilization by design' approach may be generally applicable to the production of soluble forms of other dimeric, trimeric and tetrameric single-span membrane proteins for functional and structural studies.
|Daniel A Andrews; Meng Xie; Victoria Hughes; Matthew C Wilce; Anna Roujeinikova
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Publication Detail:
|Type: Journal Article; Research Support, Non-U.S. Gov't
Journal Detail:
|Title: Journal of the Royal Society, Interface / the Royal Society Volume: 10 ISSN: 1742-5662 ISO Abbreviation: J R Soc Interface Publication Date: 2013 Feb
Date Detail:
|Created Date: 2012-11-29 Completed Date: 2013-05-01 Revised Date: 2014-02-14
Medline Journal Info:
|Nlm Unique ID: 101217269 Medline TA: J R Soc Interface Country: England
Other Details:
|Languages: eng Pagination: 20120717 Citation Subset: IM
Export Citation:
|APA/MLA Format Download EndNote Download BibTex
|MeSH Terms
Amino Acid Sequence
Bacterial Proteins / chemistry*, isolation & purification
Chromatography, Gel
Circular Dichroism
DNA Primers / genetics
Models, Molecular*
Molecular Motor Proteins / chemistry*, isolation & purification
Molecular Sequence Data
Protein Conformation*
Protein Engineering / methods*
Recombinant Proteins / chemistry*, isolation & purification
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Reg. No./Substance:
|0/Bacterial Proteins; 0/DNA Primers; 0/Molecular Motor Proteins; 0/MotB protein, Bacteria; 0/Recombinant Proteins
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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Drupal 7.X for Content Managers
Written in layman terms, this manual is intended for content managers, editors and maintainers of websites based on Drupal 7.X.
It contains step-by-step descriptions and screenshots for such processes as adding new content, updating and deleting content, uploading images, understanding taxonomy (categories) and setting basic site information. You can easily navigate in the book with the cross-links.
It also offers some useful tips and troubleshooting suggestions to help you maintain and promote your site.
This basic but packed 18-pages tutorial is based on needs and demands of real "non-geeky" folk working with Drupal sites. The eBook will let you or your customers or employees to understand Drupal content management in very short time.
Format: PDF e-book.


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Moving past gender barriers to negotiate a raise
Mar 28, 2014
Discrimination persists in the workplace and can emerge when women act as their own advocates to seek a raise, experts say.
The price of happiness in the workplace
Mar 9, 2012
Commentator Teresa Amabile on the misconceived correlation between paychecks and joy.
8 ways to get what you want from your boss
Oct 1, 2010
This weekend on Marketplace Money, Alison Green of the blog Ask a Manager talks with host Tess Vigeland about how to ask for a raise, even in a r...


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|Home Movies Music Celebs Gallery Down South Videos Downloads eCards Search RSS
|Scoop Home Bollywood Music Down South Fashion Interviews News & Happenings Hollywood
Corporate : Review
08th July 2006 22.00 IST
By Aparajita Ghosh
After exposing the underbelly of the glitterati in Page 3 , filmmaker Madhur Bhandarkar now steps into the boardroom.
In his latest film Corporate , Bhandarkar takes a dig at the corporate world and exposes the depravity that has become an intrinsic part of the business culture in the times of cutthroat competition.
'Corporate' stars Bipasha Basu , Kay Kay Menon , Rajat Kapoor , Raj Babbar , Minissha Lamba , Sammir Dattani , Harsh Chaya and Lillete Dubey.
Through a simplistically told story of rivalry between two business houses, Bhandarkar brings to light the covert business tactics and the underhand ploys that are played in the game of one-upmanship between two industrialists. In the thick of this corporate tussle, Bhandarkar places the central character of his story - a smart and ambitious executive, played by Bipasha Basu.
The film has Rajat Kapoor and Raj Babbar playing two bitter rivals. Vinay Sehgal (Rajat Kapoor) and Dharmesh Marwah (Raj Babbar) are the MDs of their respective companies, Sehgal Group of Industries and Marwah International Private Limited.
While Sehgal is a stylish and modern entrepreneur, Marwah is a traditional, superstitious businessman who takes advices from his spiritual guru and wears gemstones to bring him good luck in business.
Nishigandha (Bipasha Basu) is a top executive working for Vinay Sehgal. She is clever, sly and often uses manipulation and deceit to get the work done.
Sehgal's brother-in-law Ritesh (Kay Kay Menon) joins the company. Ritesh and Nishi are more than colleagues. They share love for each other.
Things gather pace after Nishi manages to steal a business plan from Sehgal's rival Marwah. The plan is about a cola brand that Marwah plans to launch. To kill the competition at its very root, Sehgal launches a similar product before Marwah. But Marwah won't take it lying low. He will hit back at Sehgal.
In the process, Nishi's conscience is shaken as she sees basic moralities and ethics abandoned in the race for profits and one-upmanship. She also ends up paying a huge price for her ambition.
'Corporate' showcases the acting talent of Bipasha Basu. The actress, usually seen as a glamorous siren, has shed her typical image and given a performance full of subtle nuances. She brings in her character a right mix of toughness and vulnerability, cunningness and repentance.
Rajat Kapoor and Kay Kay Menon are two other actors who stand out. Rajat fits the role of a shrewd and guileful businessman to t. Kay Kay Menon speaks through his facial expressions. On the other hand, Raj Babbar underplays his character commendably. He convincingly plays the traditional, emotional businessman who, however, is not without moral corruption.
Minissha Lamba and Sammir Dattani have very brief roles in the film.
The first half of 'Corporate' is a bit of a drag, with all the business parlance and corporate lingo. The movie picks tempo after the interval and the story sort of reaches a crescendo with a moral lesson that perhaps one shouldn't get involved in one's job too seriously.
Although 'Corporate' is a well intended movie that deals with a subject that hasn't often been told in Hindi films, but the movie eventually talks about the same business tactics and manipulations that even a layman might be aware of. And in doing so, the film actually reeks a bit of cynicism. The truth remains that there is more to the corporate world than just deceitful dealings and betrayals. At the end of the day, the film will have you believe that many of the executives in their well-preened suits and ties are morally bankrupt within.
If only this cynicism and angst can be compromised with, 'Corporate' emerges as a good movie that ought to be seen once.
Page 3
Madhur Bhandarkar
Bipasha Basu
Kay Kay Menon
Rajat Kapoor
Raj Babbar
Minissha Lamba
Sammir Dattani
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"Only the 2nd time in 40 years"
I have read &/or listened to more that 5000 books over the last 40 years. In all that time and with all those opportunities I have not finished only one title - until this book. For only the 2nd time in 40 years I did not finish a book that I had started. Believe me when I declare that I have had the urge to quit several other times, but managed to perservere. However, I just could not justify wasting any more time on a volume that provided no enjoyment or satisfaction. Actually, I did get some satisfaction by stopping the audio player. The producer's hype was terrific. The presenter did a very good job. The subject matter was geared to an intelligent 12 year old and left me cold. I wasted a credit and wish that there was some way to return it to Audible like an inedible meal at a restaurant.
"Vivat Bobo! Vivat Eszterhazy!"
Somewhere in the top 25
The raid on the Brigand's compound.
More variation in tempo and more lingering on some of the memorable lines.
I'm VERY familiar with this book. I've owned it for three decades and am delighted to find it on Audible.
Grandma bibliophile! Audible books make reading with an active life possible.
"Whimsical read."
These stories may have been better for me in written form. I'm not sure if it was the narrator the story or what, but I lost track of the plot frequently and had to back up. I am easily distracted, but not usually during a good book. I almost gave 3 stars, but what I did hear I enjoyed so I decided not to rate the book on my ability to pay attention. I think that is because it wasn't so much one of my preferred types of books. Parts of it were just funny, but that isn't usually enough to keep me enthralled.


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Anecdote - Making Strategy Stick
By Years
I read a really interesting interview this morning with Jason Fried, founder and CEO of 37signals, a software company based in Chicago.
37signals are renowned for being real innovators in the way they run their business. For example they shortened their workweek from 5 to 4 days for all their people during summer.
What caught my attention in the interview was his comments about what actually matters for a business.
He argues that instead of the business worlds and medias fascination with how much money a company is making or how many employees they had, they instead should be focussing on four things – the things that really matter.
Fried says what really matters is:
What a fantastic criteria to measure the success of your business.
About Kevin Bishop
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Posts tagged with Affordable Housing
Lawrence lands on more national lists; a bike repair station at City Hall; details on city's latest affordable housing project
I am woefully behind on telling you how much other people like us. In short: Quite a lot. That's my way of saying that Lawrence and some Lawrence businesses have landed on more national lists.
We'll start in the world of restaurants. The travel website The Culture Trip has put together a list of the "10 Best Restaurants in Kansas." Downtown Lawrence is home to four of the 10. This is a sign of one of two things: 1. Downtown Lawrence truly is the culinary capital of Kansas. 2. A Culture Trip editor had one too many Ad Astra Ales at Free State and never made it to any other city. (Raise your hand if that has happened to you.)
Regardless, Free State Brewery is on the list. The article also touts The Burger Stand, 715 Restaurant and Merchants Pub and Plate. Restaurants in Manhattan, Council Grove, Wichita, and Kansas City all made the list as well. The one that sounded the most interesting, though, was in Assaria, a town of about 400 people in Saline County. The Renaissance Cafe operates in the former Assaria High School. According to the article, tables are arranged on the old gym floor, and stocked bookshelves are a fixture of the restaurant. Hopefully, it still has a place to hang up heavily adorned letter jackets because this sounds like a place I need to visit.
In terms of Lawrence's other ranking, the website CollegeRanker has Lawrence ranked as No. 2 on its 50 Best College Towns to Live in Forever. I suspect this also has something to do with Free State beer, although the article doesn't own up to it. Instead, it lists Lawrence's thriving music scene, and mentioned a 2007 ranking that listed The Replay Lounge as one of the top 25 bars in America. When you are talking about forever, it is very important to have a good bar nearby.
Manhattan also made the list at No. 26. I'm not really sure what criteria was used to rank these towns, but Lawrence finished one spot ahead of Ft. Collins, Colo., and one spot behind our arch rival . . . St. Augustine, Fla., home to Flagler College.
In other news and notes around town:
• If I were creating a list of the best places to get a flat tire on your bike in Lawrence (I know, there's already an online list for that, but play along), Lawrence City Hall would be near the top of it. Why? Because the city has recently installed a bicycle repair station outside the east entrance.
In case you think I'm jesting, here's a picture.
The repair station has several hand tools secured via cables. Tightening a loose nut or making chain repairs, brake adjustments and that sort of thing can be done at the bike station. It also has an air pump, and despite it being located at City Hall, it does not dispense hot air. (Calm down, people. It's all right. I'm sure politicians make good-natured jokes about journalists from time to time.)
The bike repair station is actually something to keep an eye on. There has been a lot of talk about making Lawrence more pedestrian and bicycle friendly. This bike station is meant as a pilot project. City staff members will monitor use and feedback from the bicycle community. If bikers find it useful, there may be others installed along frequent bike routes and trails.
• Another big topic in the city is affordable housing and attracting retirees. Commissioners at their meeting Tuesday night provided a boost to both efforts. As we reported, the city provided about $100,000 in incentives via fee rebates and some in-kind infrastructure work for Tenants to Homeowners' Cedarwood Senior Cottages project at 2525 Cedarwood Ave. in south Lawrence.
Now that the project has the key city approval, Rebecca Buford, executive director of the not-for-profit Tenants to Homeowners, said she hopes the 14-unit townhome project will be ready for tenants this time next year. Dirt work already has begun on the site, which is behind the United Way building.
Buford also gave me some details about rent rates. Nine units will serve low-income seniors, and they'll rent from $527 to $687 per month, depending on whether it is a one-bedroom or two-bedroom unit. Five units will be reserved for low-to-moderate income seniors, and they'll rent for about $795 per month.
Buford estimates that the units — which have garages, front and back porches, fiber optic wiring, a community center and shared gardens — will rent for about $200 to $300 less than standard market rates in Lawrence.
Seniors will have to meet income guidelines to qualify. Buford said her organization is putting together an information packet for prospective tenants, but already she has a list of more than 50 people who are interested. If you want to be added to the list, call the Tenants to Homeowners office at 842-5494.
Buford said she hopes the Cedarwood Project will serve as template for Tenants to Homeowners to build other such senior, affordable housing in other neighborhoods.
"The demand for this type of housing is very strong," Buford said.
Topeka-based financial services company moving headquarters to west Lawrence; city moving ahead with ice rink; new affordable housing coalition forms
I've gotten word that a Topeka-based financial services company is moving its corporate offices and about 35 well-paying jobs to Lawrence.
Personalized Brokerage Services is moving into about 8,000 square feet of space at the Wakarusa Corporate Centre near 18th and Wakarusa Drive in west Lawrence. Renovation of the space is nearly complete, and the company is expected to move in next week, said Randy Goldsmith, the commercial real estate agent with CB Richard Ellis who brokered the deal on behalf of the Corporate Centre's ownership group.
Personalized Brokerage Services — or PBS as it frequently brands itself — is part of Allianz Life Insurance Company of North America, which in turn is part of Allianz SE, which operates the PIMCO fund and other large financial institutions.
PBS is a company that provides a host of business services to independent financial services companies. According to online job listings for PBS, the company offers advertising, public relations, media planning, interactive design, lead generation, strategic planning and several other services to independent brokers and others in the financial services industry.
It looks like the company has been in business for about 25 years. I've got a call into the company to try to find out more information about the pending move.
Goldsmith said the company began looking at moving to Lawrence because it had several employees who lived in Lawrence and Kansas City. In Topeka, the company was based in an office park near Wanamaker Road and Interstate 70.
"It will be a good company for Lawrence," Goldsmith said. "There is no doubt about that."
The deal also is another sign of renewed momentum for the Wakarusa Corporate Center. If you remember more than a decade ago, the Wakarusa Corporate Centre was planned to be about a 300,000 square-foot office development with four buildings on a campus-like setting. Only the first building was ever constructed, and office demand in Lawrence ended up being weaker than expected. But in recent years, the building has been successful in attracting some larger companies, particularly some companies looking to move from Topeka to Lawrence.
The Corporate Centre's other large tenant is Great American Insurance, a crop insurance company that moved about 60 employees from Topeka to Lawrence in 2007. That deal was brokered by Lawrence businessman Greg DiVilibiss, who was a leader of the former ownership group that developed the center and still owns much of the vacant ground around the office building.
Goldsmith said the building is now 88 percent leased, and he's in discussions on some other deals to fill the remaining space.
In other news and notes from around town:
• As I mentioned, PBS is part of the insurance behemoth Allianz, and it is looking more likely that I'm going to need to update my insurance policies. Why? Two words: Ice skates.
The idea of a seasonal, outdoor ice skating rink in downtown Lawrence is moving closer to reality. Officials with Lawrence Parks and Recreation have told me they have won approval from the board of the Lawrence Public Library to proceed with plans for a seasonal rink that would operate in the plaza area between the expanded library and the new city-owned parking garage.
Now, parks and recreation leaders just need to get city commissioners to approve what is expected to be up to $130,000 in expenditures to purchase the necessary equipment for the rink. We first reported on the idea in December, and noted that it had some good support from City Manager David Corliss, who is interested in finding ways to draw more people to downtown during the winter shopping season.
But we subsequently reported that library leaders had some concerns. Recently, though, architects have completed conceptual plans for the plaza area between the library and the parking garage, and were able to show how the ice rink could fit into the space and still leave lots of rooms for other uses in the area.
Ernie Shaw, the city's director of parks and recreation, said current plans are for the ice rink to be in place from about Thanksgiving to New Year's. The city hopes to find a corporate sponsor for the rink, and also would charge an admission fee to skaters. The department is planning to hold down operating costs by using artificial ice, which cuts down on the energy bills needed for refrigeration of a traditional rink.
Shaw said Gladstone, Mo. operates a community rink with artificial ice, and reviews of the surface have been good there and elsewhere that it is used.
The Lawrence rink, which is proposed to be 60 feet by 80 feet, would be on one of three large terraces planned for the plaza area. The rink would be on the terrace closest to Vermont Street, and would be in front of a large bank of windows in the library.
"If they wanted, parents could sit in the library and look out over the ice rink while their kids skated," Shaw said.
As for the plaza area, Shaw said he thinks there is a lot of potential for unique events.The plaza area could easily accommodate more than 200 people, Shaw said. The system of three terraces will create a kind of a natural amphitheater to host performances. Shaw said architects are designing the area with plenty of electrical connections to accommodate the needs of bands and other performers. The adjacent parking garage also was built with public restrooms designed to serve events taking place at the plaza.
"The area is not going to accommodate concerts of 10,000 people or anything like that, but it is going to be a nice area for a variety of events," Shaw said.
Shaw said the Lawrence Public Library always will have first opportunity to book events for the plaza area, but he said the parks and recreation department will maintain the area and will operate a booking system for the plaza.
Shaw said he hopes to have information to present to city commissioners about the ice rink within the next one to two months. He said the department's goal is to have the rink in place for the 2014 holiday season.
• If you are interested in the issue of affordable housing in Lawrence, there's an event this evening (Wednesday, May 14) that may interest you. A new group called the Lawrence Affordable Housing Coalition is meeting at 7 p.m. in the conference room of the Sandbar Subs/Peoples bank building at Eighth and New Hampshire streets.
The group is being led by Robert Baker of Lawrence's Tenants to Homeowners, and Leslie Soden, a former Lawrence City Commission candidate and East Lawrence neighborhood leader.
The idea of a lack of affordable housing in Lawrence was an issue you heard a lot about in the late 1990s and early 2000s. In recent years, the issue hasn't gotten as much discussion, but Soden told me it deserves more attention.
The coalition took note of a recent Journal-World article that reported federal figures found Lawrence to be the most expensive city in the state to live, because of its high housing prices and relatively low incomes. The coalition also has been doing its own research. It estimates Lawrence renters in an average two-bedroom apartment would need to have jobs that pay at least $16.54 per hour in order to avoid spending more than 30 percent of their monthly incomes on housing.
Some cities — see a recent plan by New York City – have been using new government regulations to encourage more affordable housing. Soden said she doesn't have any specific solutions she is pushing for as part of the coalition's work. Instead, she said the first few meetings of the group will be designed to set some goals and figure out a more specific mission for the new organization.
More LJWorld City Coverage
Signs indicate Freebirds Burrito has closed downtown Lawrence location; new plan emerges for affordable housing near 23rd and O'Connell
The free bird has perhaps decided to fly away. There's a new sign hanging from the window of the Freebirds World Burrito in downtown Lawrence that indicates the restaurant has closed.
The sign came to my attention yesterday, and I've been trying to get in touch with the restaurant's spokeswoman ever since, but with no luck. The sign apologizes for the inconvenience and reads, "Freebirds has closed indefinitely in Lawrence. Please come visit our other locations in Kansas City."
Make of that what you will. That's the thing about indefinitely. It is just not definite enough for my tastes. But assuming that the restaurant's run in Lawrence is over, it is a bit of an unexpected departure. The restaurant — which served a variety of burritos, tacos, adult beverages and the like — opened its doors in late January of 2013.
Freebirds went into a big space — the former Maurices clothing store — that had sat vacant for a long time after the clothing retailer moved to South Iowa Street. It sure looked like Freebirds spent some good money to renovate about two-thirds of the space. The other third was put up for lease, but a tenant hasn't yet been found. If Freebirds is done, then downtown Lawrence once again has one of its larger Massachusetts Street storefronts sitting vacant.
It will be interesting to watch. The space sat vacant for about three years after Maurices left downtown Lawrence in 2009. The economy was much different back then, so who knows what the prospects for the building may be now. Although I haven't heard any rumblings, I suppose it is possible Freebirds is leaving because someone has expressed interest in the entire Maurices space.
I'll keep my ears open for news on the space. In the meantime, it is probably best that we all remember the words of a famous poet — who we have forgotten the name of — who wrote: Set the bird free. If it is true love, it shall return. Or something like that.
For those of you who loved Freebirds, I'm not sure where that leaves you. I guess, watch the sky for a bird with an overstuffed burrito hanging from its beak.
In other news and notes from around town:
• The idea of Lawrence becoming home to senior citizens and retirees continues to be a strong one. An Olathe senior housing company has confirmed it is trying to put together a deal for a 90-unit senior living community near 25th Terrace and O'Connell Road in southeast Lawrence.
The proposed developer is Wheatland Investments, which has about 500 apartment units across the region, according to a letter from its managers, David and Suzanne Rhodes.
The project isn't a done deal, however. In addition to needing the necessary city approvals, it also is competing for affordable housing tax credits from the state. Without those tax credits, I would guess the project may have to go back to the drawing board. The credits would make the apartments rent controlled, and would mean that tenants would have to meet some income guidelines.
The credits also can be used to provide housing for low income individuals, but, according to the letter, Wheatland is interested in making the project exclusively for senior citizens 55-years and older. The concept plan calls for 15 buildings, each housing six garden/ranch style apartments. The project would be spread out over nine acres near the intersection.
Lawrence city commissioners at their meeting tonight will receive a request from the developers to issue Industrial Revenue Bonds, which would qualify the approximately $8 million project for a property tax abatement. But commissioners aren't being asked to approve the request tonight. Instead, they're being asked to send the request to city staff members for review and analysis.
The site is just south of of the proposed site for another affordable housing project. As we previously have reported, the Lawrence-Douglas County Housing Authority has been working on a partnership with a group led by Lawrence businessman Bill Newsome to develop an approximately $15 million affordable housing project for working families.
But Shannon Oury, executive director of the Lawrence-Douglas County Housing Authority, told me this morning that project has suffered a setback. Interest rates have risen, and that has created complications for the financing of the project.
"We're in a situation of reevaluating how we make that work," Oury said.
She said the group didn't have a timeline for determining when or if that project would move forward.
More LJWorld City Coverage
Tenants to Homeowners files plans for independent, senior living project in south Lawrence
If Lawrence really wants to become a destination for retirees, Rebecca Buford, executive director of Lawrence's Tenants to Homeowners, believes there is an issue community leaders might want to think about: an affordable place for retirees to live.
"If we really want seniors to come live here, we should think about this," Buford said. "We don't want them locking up all their money in housing. We want them to have money available to spend in Lawrence."
Buford and her not-for-profit agency have filed plans to build a 14-unit, rent-controlled, senior living housing development on property just behind the United Way building in south Lawrence.
Tenants to Homeowners has filed a request to rezone about 2 acres of vacant property at 2518 Ridge Court to RM-12 multi-family zoning. The property currently is zoned for RS-7 single family development.
Buford said concept plans call for the property to be developed with a mix of one-bedroom and two-bedroom townhouses that will be limited to seniors 55 and older.
Buford said a group of retirees or soon-to-be retirees approached Tenants to Homeowners about the project, saying that Lawrence needed more retirement housing that "felt like a neighborhood instead of a high-rise apartment complex."
Buford said current plans call for Tenants to Homeowners to rent the properties to seniors rather than sell the townhouses. Buford said feedback from several retirees indicated they would rather rent than own.
"Seniors don't want to lock all their equity up into their homes," Buford said. "They usually need access to their equity for health care and other expenses."
The units will rent for below-market rates, and seniors must meet certain income guidelines to qualify for a unit. Buford said the project will be geared at those seniors who make 80 percent or less of the area's median income. For a family size of two, that means an annual income of $45,350 or less.
The property currently is owned by Douglas County. It was part of the old Valley View Nursing Home that the county operated decades ago. Buford said plans call for the county to donate the property to Tenants to Homeowners, which will help the project offer below-market rates. Buford said she also is working to secure grants and other financing for the approximately $2 million project.
If the City Hall land use approvals come through in a timely fashion, Buford hopes to break ground next spring and be ready to open by late 2014.
Buford acknowledges the project may face opposition from a few neighbors, which is often the case when vacant ground in an established neighborhood is proposed to be developed. This one comes with the added hurdle that Tenants to Homeowners is asking for a zoning category that often is used to build apartments. But Buford said Tenants to Homeowners is committed to the idea of townhouse development rather than a traditional apartment complex. And she said the development will place restrictions on the land to ensure that it always remains limited to senior housing.
But this may be one project that hits City Hall with a lot of momentum. It is combining two trends that have been getting a lot of talk locally: affordable housing and attracting retirees. There was an entire joint city-county task force on attracting retirees to the city.
And this is the third affordable housing project to surface in recent months, joining the public-private proposal by the Lawrence-Douglas County Housing Authority at 23rd and O'Connell, and plans for a new four-story development near the Poehler Lofts building in East Lawrence. By the way, Buford confirmed to me that Tenants to Homeowners has agreed to be a partner in that project, which will feature 43 units in a newly-constructed building at the southeast corner of Ninth and Delaware streets.
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Amber Case is an entrepreneur and researcher helping Fortune 500 companies design, build, and think about connected devices. She is the co-founder and former CEO of Geoloqi, a location-based software company acquired by Esri in 2012. She spoke about the future of the interface for SXSW 2012's keynote address, and her TED talk, "We are all cyborgs now", has been viewed over a million times. Named one of National Geographic's Emerging Explorers, she's been listed among Inc Magazine's 30 under 30 and featured among Fast Company's Most Influential Women in Technology.
Case is the author of An Illustrated Dictionary of Cyborg Anthropology and Designing Calm Technology from O'Reilly Books (Fall 2015). She is a passionate advocate of privacy and the future of data ownership, and is interested in furthering the ideas of Calm Technology, wearable computing, and the future of the interface. Her previous work as Managing Director of Existence at Healthways involved predictive analysis and wellness. Amber lives and works in Portland, Oregon; you can follow her on Twitter @caseorganic and learn more at caseorganic.com.
Speaking and Consulting
Case is a welcomed speaker across many verticals. From colleges and universities to conferences and lunches, Case is just as comfortable speaking in front of large audiences as she is at smaller gatherings. To book Amber Case for a speaking engagement, contact Monica Davis at monica dot davis at caseorganic dot com. Note: Amber Case is currently booked until January 2016.
Book Amber Case for a Speaking Engagement.
Press Kit
Click for high resolution photos of Amber Case. All photos credit Daniel Root.
Calm Technology: Designing for the Next Generation of Devices
O'Reilly Books, Oct 2015
Available through O'Reilly's Prerelease program Summer 2015.
Follow @calmtech for updates.
Case's perspective on the Internet of Things totally re-wires our view of technology. Researchers at XEROX Parc were tackling the problems facing the Internet of Things back in the 70s, but now, too many people in tech are making the same mistakes, with executives intent on adding new features to their devices, because that's the model they're used to.
In the next 5-10 years, we're going to have a whole class of connected devices, but we're still focused on building technology that's complex and code heavy. We're already encountering this problem now, with heavy applications struggling to work on connected smartphones with minimal battery life and consumer attention. So we're going to see a return to lower level device languages — LEGO-type projects that reward interoperability, instead of the walled gardens we have now. Expect a massive sea change, because successful technology for the IoT era will become really simple, with minimal interfaces. The future of the Internet of Things will be driven by "Calm Technology" – elegant, humane, unobtrusive.
An Illustrated Dictionary of Cyborg Anthropology
CreateSpace, Jan 2014
with Maggie Wauklyn (Illustrator), Douglas Rushkoff (Introduction)
What does it mean to have an online persona? How is technology changing the way we work, live and play? How do our tools influence the way we interact with the world? Technology is intertwined with almost every aspect of our lives. Our cell phones, cars and laptops have turned us into cyborgs. Cyborg Anthropology is a way of exploring how we live as a connected species.
This book explores topics such as junk sleep, hyperlinked memories, panic architecture, the quantified self, and how humans are changing through the use of technology. This book is an appetizer for an emerging field of study, an inspirational starting point for designers, developers, researchers, students, and anyone who wishes to explore the symbiotic relationship between technology and culture.
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November 30, 2015
KNOXVILLE, Tenn. (WVLT) -- Publix Supermarkets opens its first store in Knoxville on Thursday.
The store, located in Northshore Town Center just off I-140 in West Knoxville, opens at 7 a.m. Thursday following a 6:45 a.m. ribbon cutting.
The store estimates it will employ around 200 people.
Publix was ranked by Fortune magazine as the 67th best company to work for in 2011.
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So what a year it has been! (I always intend to be better at posting but…..life?)
Anyway, our baby girl turned one in January!! I can't believe it has been a whole year already!! We are so blessed by this beautiful, crazy, light in our life. :)Her great grandma made the cake. She got her own cupcake though, no sense in was wasting an entire cake!! I think she enjoyed it though. ;)
So we had a wonderful time celebrating our little girl and were incredibly blessed by the friends and family that came to bless and celebrate her too.
So in other news, lets see….Nathan got a new position within Cerner that he is LOVING. I love seeing him really enjoy his work. :) I have been thinking of trying to make and sell tutus, like the one I made Bekah. We also have decided to tape verses to our mirror to help us with Bible memorization. We are really liking having them up as a reminder.
OHhhh….right. The big news. :)
Yeah….we are very excited to welcome a new Mayberry to our family sometime around Oct 1st. :) Bekah, in honor of the occasion has even learned a new word. "baby"


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The competition between the convenience of using tablet products and the versatility of laptop computers.
Currently on the market, there are many different kinds of tablets at various prices for users to choose from. Tablets will inevitably take the place of laptop computers in the near future. However, tablet devices can not replace the laptops. So what makes the better device for the everyday activities? This article will give you a comprehensive look at this issue.
A pro of using a laptop is its portability, you can use the full functionality of a desktop computer while sprawled on the sofa or in bed.
Most users feel laptop keyboard is easier to use than the touch pad, you can type quicker and more accurate. The average screen size of a laptop is around 13 inches, which is larger than the 10-inch tablet. When using your laptop, you will not have to worry too much about accidentally scratch or damage the screen because replacement is not a too difficult issue.
However, a minus point for the laptop is that it's quite heavy and bulky compared to the tablet. Some manufacturers overcome this disadvantage by reducing the size and weight of their laptop, but that means the cut in decent features needed.
Tablet is more portable than a laptop. They are small, lightweight and flat so users can comfortably hold and interact with them. Tablet is very handy for people who work in highly creative because you can draw or write directly on the screen by hand or pen at any time.
However, they are fragile. Along with that is the limited in functionality when comparing to the laptop. Another minus point is that tablet computers do not have CD drives, USB flash drive in addition to the limited memory. Many websites still do not have an optimized version for mobile devices so accessing the Internet is sometimes limited when using this device.
Laptop + Tablet?
Ultrabook or hybrid tablet is the perfect solution for this problem. With separate accessories such as keyboard or mouse, tablet devices become the perfect choice for those who want to replace the laptop.
HP Envy X2
Currently, there are many measurements that manufacturers made to neutralize the weaknesses and strengths of the two types of devices. For example, the introduction of the ASUS Transformer Book with the screen can be taken off so that you can use it as a laptop or a tablet. Another solution is to equip the tablet with a wireless keyboard and mouse for user "allergic" to the touch keyboard.
To conclude
In the race between the laptop and tablet, no one is the winner. Honestly, no one can answer the question which makes the better device rather than the users and their intended use.
If you need highly mobility, select a tablet. Also if the job requires full PC features, then laptop is the top choice.


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April showers bring May flowers, but here at Southwest Airlines, April showers bring… Urban Gardening!!
Last Earth Day, we posted about our Network Planning Department's efforts to create the SWA Community Garden. One year later, we are happy to say that the efforts have been "fruitful." Or… rather, "produce-tive."
Two years ago, the Garden's Master Green Thumbs, Jamie Ibarra and John Jamotta, began collecting compost for the Garden. They recruited Eurest, the company which operates Headquarters' eatery, "The Landing," to help. From that relationship, the garden has received a steady supply of organic compostable materials to create a rich soil in which the plants may thrive. Since then, the growing hasn't stopped.
Currently 14 volunteers regularly cultivate the Garden, which has now grown to include 2,500 square feet. This past season, the Team harvested potatoes, cantaloupe, watermelon, peppers, tomatoes, corn, pumpkins, squash, and cucumbers.
So, just where do the yields from the Garden go? In the past year alone, the Garden team took six trips to the local Dallas food bank. Each time, the group brought a donation of the crops grown in the Community Garden.
Another point of pride for the group is their commitment to organic and earth-friendly practices. In taking care of the plants, the team strives to be water-wise and conserves natural resources. To further learn about organic gardening, the team has developed a close relationship with the local Texas Agri-Life Extension office.
Keeping true to their theme to "Learn and Teach" about organic gardening and food harvest donations, the team always welcomes more help and is looking to expand the Garden. Since the Community Garden is a 100 percent volunteer-driven effort and operates entirely without money from Southwest Airlines, the Team deserves a huge round of applause for their commitment to the Community Garden!
If you have a Green Thumb and would like to share gardening tips, please post your comments below. DING! You are now free to be Green and have a Happy Earth Day!
Happy Earth Day: A Big Green Thumbs Up!
April showers bring May flowers, but here at Southwest Airlines, April showers bring… Urban Gardening!!


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By Darren Silverman, APO
IsoFilms options futuristic revenge tale "Carnival Horror" from writer Jared Cohn.
By Anonymous
Actor Jason Vail, who previously starred in the popular book trailer Abraham Lincoln: Vampire Hunter on Youtube plays a lead role in The Asylum's latest feature, "Abraham Lincoln Vs Zombies" playing opposite Bill Oberst Jr. as Honest Abe.
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Ultra-protective tidal volume: how low should we go?
1 Cardio-Pulmonary Department, Pulmonary Division, Hospital das Clínicas, University of São Paulo, Av. Dr. Arnaldo 455, sala 2144 (2nd floor), São Paulo, SP, Brazil. CEP: 01246-903
2 Research and Education Institute of Hospital Sírio Libanês in São Paulo, R Cel Nicolau dos Santos, 69, São Paulo, Brazil. CEP: 01308-60
Critical Care 2013, 17:127 doi:10.1186/cc12556
See related research by Retamal et al., http://ccforum.com/content/17/1/R16Published: 28 March 2013
Applying tidal volumes of less than 6 mL/kg might improve lung protection in patients with acute respiratory distress syndrome. In a recent article, Retamal and colleagues showed that such a reduction is feasible with conventional mechanical ventilation and leads to less tidal recruitment and overdistension without causing carbon dioxide retention or auto-positive end-expiratory pressure. However, whether the compensatory increase in the respiratory rate blunts the lung protection remains unestablished.


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UPMC shouldn't fear healthy competitionAugust 27, 2014 12:00 AM
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UPMC's latest financial statement makes a point to highlight growth in its own insurance plan membership as well as all its other corporate metrics ("Chief Financial Officer Says UPMC Is Holding Its Own," Aug. 21). Since it has accomplished this while competing with Highmark, UPMC concedes an essential point: Competition among health care providers and insurers is a good thing.
Now UPMC wants to get rid of its competition and is willing to throw the region into chaos, leaving patients and employers with little information and great uncertainty.
UPMC should look to its own quarterly report as a sign that competition will help both Pittsburghers and its own financial health.
Executive Director
Pittsburgh United
North Side