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Network structures and algorithms in Bioconductor.

UNLABELLED: In this paper, we review the central concepts and implementations of tools for working with network structures in Bioconductor. Interfaces to open source resources for visualization (AT&T Graphviz) and network algorithms (Boost) have been developed to support analysis of graphical structures in genomics and computational biology. AVAILABILITY: Packages graph, Rgraphviz, RBGL of Bioconductor (www.bioconductor.org).

Algorithms↗

Development and extensive sequencing of a broadly-consented Genome in a Bottle matched tumor-normal pair.

The Genome in a Bottle Consortium (GIAB), hosted by the National Institute of Standards and Technology (NIST), is developing new matched tumor-normal samples, the first to be explicitly consented for public dissemination of genomic data and cell lines. Here, we describe a comprehensive genomic dataset from the first individual, HG008, including DNA from an adherent, epithelial-like pancreatic ductal adenocarcinoma (PDAC) tumor cell line and matched normal cells from duodenal and pancreatic tissues. Data for the tumor-normal matched samples comes from seventeen distinct state-of-the-art whole genome measurement technologies, including high depth short and long-read bulk whole genome sequencing (WGS), single cell WGS, and Hi-C, and karyotyping. In future publications, these data will be used by the GIAB Consortium to develop matched tumor-normal benchmarks for somatic variant detection. We expect these data to facilitate innovation for whole genome measurement technologies, de novo assembly of tumor and normal genomes, and bioinformatic tools to identify small and structural somatic mutations. This first-of-its-kind broadly consented open-access resource will facilitate further understanding of sequencing methods used for cancer biology.

Journal Article↗

Exploring endothelial cell environments across organs in spatially resolved omics data.

Endothelial cells are ubiquitously present in the human body and line the luminal surface of blood and lymphatic vessels. The oxygen-dependence of cells impacts their proximity to blood vessels, and consequently, to endothelial cells depending on their functional properties and priorities. This paper presents cell-to-nearest-endothelial-cell distance distributions for various cell types using 399 spatially resolved omics datasets from 14 studies comprising 12 tissue types with a total of 47,349,496 cells. Additionally, we developed an open-source web-based interactive tool, Cell Distance Explorer, that allows researchers to interactively visualize cell graphs and linkages in 2D and 3D datasets. Finally, we present a hierarchical neighborhood analysis focused on the endothelial cell neighborhoods in small and large intestine datasets. This paper provides an open-access resource (datasets, tools, and analyses) to characterize and compare cell distances and cell neighborhoods in spatially resolved omics data.

Journal Article↗

Chaos-induced coherence in two independent food chains.

Coherence evolution of two food web models can be obtained under the stirring effect of chaotic advection. Each food web model sustains a three-level trophic system composed of interacting predators, consumers, and vegetation. These populations compete for a common limiting resource in open flows with chaotic advection dynamics. Here we show that two species (the top predators) of different colonies chaotically advected by a jetlike flow can synchronize their evolution even without migration interaction. The evolution is characterized as a phase synchronization. The phase differences (determined through the Hilbert transform) of the variables representing those species show a coherent evolution.

Animals↗

Recent advances in rice biotechnology--towards genetically superior transgenic rice.

Rice biotechnology has made rapid advances since the first transgenic rice plants were produced 15 years ago. Over the past decade, this progress has resulted in the development of high frequency, routine and reproducible genetic transformation protocols for rice. This technology has been applied to produce rice plants that withstand several abiotic stresses, as well as to gain tolerance against various pests and diseases. In addition, quality improving and increased nutritional value traits have also been introduced into rice. Most of these gains were not possible through conventional breeding technologies. Transgenic rice system has been used to understand the process of transformation itself, the integration pattern of transgene as well as to modulate gene expression. Field trials of transgenic rice, especially insect-resistant rice, have recently been performed and several other studies that are prerequisite for safe release of transgenic crops have been initiated. New molecular improvisations such as inducible expression of transgene and selectable marker-free technology will help in producing superior transgenic product. It is also a step towards alleviating public concerns relating to issues of transgenic technology and to gain regulatory approval. Knowledge gained from rice can also be applied to improve other cereals. The completion of the rice genome sequencing together with a rich collection of full-length cDNA resources has opened up a plethora of opportunities, paving the way to integrate data from the large-scale projects to solve specific biological problems.

Journal Article↗

Implementing an interdisciplinary healthcare quality project.

Bringing together healthcare professionals from several disciplines for a quality project can provide many benefits. This article describes the collaborative process between nursing and dental services at a Department of Veterans Affairs Medical Center as they assessed and evaluated the practice of oral hygiene among 120 long-term care patients. Enhancement of interdisciplinary collaboration occurred through appropriate disciplinary representation and leadership, clarification of disciplinary vocabularies, firsthand empirical assessment, and timely feedback. With each discipline combining resources, fostering open communication, and evaluating the project, the collaborative process was optimized. Benefits of this interdisciplinary quality project included (a) more comprehensive and holistic evaluation of patients' oral hygiene practices, (b) quality assessment in a timely fashion, (c) establishment of rapport between individuals who otherwise might not have an opportunity to interact, (d) improved communication and understanding between disciplines, and (e) development of better patient care indicators.

Communication↗

Comparative transcriptomics uncovers poplar and fungal genetic determinants of ectomycorrhizal compatibility.

Ectomycorrhizal symbiosis supports tree growth and is crucial for nutrient cycling and temperate and boreal ecosystems functioning. The establishment of functional ectomycorrhiza (ECM) first requires the association of compatible partners. However, host and fungal genetic determinants governing mycorrhizal compatibility are unknown. To identify such factors in poplar and its fungal associates, we mined existing and de novo tree and fungal transcriptional datasets. We identified co-expressed genes enabling ECM symbiosis at early and mature stages of the interaction. These sets of genes can be divided into general fungal-sensing and ECM-specific components. We highlight the importance of fungal modulation of plant JA-related defenses and the regulation of secretory pathways for ECM compatibility, including upregulation of key fungal small secreted proteins, the downregulation of plant secreted peroxidases, and the downregulation of plant cell wall remodeling proteins concomitantly with the upregulation of fungal glycosyl hydrolases acting on pectin. Not only gene regulation, but also its temporal scale and dynamics seem to play a crucial role for mycorrhizal compatibility. The expression profile of the host Common Symbiosis Pathway and nutrient transporters was also studied, revealing constitutive levels of expression and moderate upregulation in compatible ECM interactions. Overall, these results underscore the importance of novel biological functions during the establishment of ECM symbiosis, help us gain insights into the molecular events determining mycorrhiza compatibility, and serve as a data-rich transcriptomic resource to open new research questions in the field.

Mycorrhizae↗

The economic burden associated with osteoarthritis, rheumatoid arthritis, and hypertension: a comparative study.

OBJECTIVE: To compare the economic burden to society incurred by patients with RA, OA, or high blood pressure (HBP) in Ontario, Canada. METHODS: Consecutive subjects recruited by 52 rheumatologists (RA) and 76 family physicians (OA and HBP) were interviewed at baseline and 3 months. Information was collected on demographics, health status, and any comorbidities. A detailed, open ended resource utilisation questionnaire inquired about the use of medical and non-medical resources and patient and care giver losses of time and related expenses. Annual costs were derived as recommended by national costing guidelines and converted to American dollars (year 2000). Statistical comparisons were made using ordinary least squares regression on raw and log transformed costs, and generalised linear modelling with adjustment for age, sex, educational attainment, and presence of comorbidities. RESULTS: Baseline and 3 month interviews were completed by 253/292 (86.6%) patients with RA and 473/585 (80.9%) patients with OA and/or HBP. Baseline and total annual disease costs for RA (n = 253), OA and HBP (n = 191), OA (n = 140), and HBP (n = 142), respectively, were $9300, $4900, $5700, and US$3900. Indirect costs related to RA were up to five times higher than indirect costs incurred by patients with OA or HBP, or both. The presence of comorbidities was associated with disease costs for all diagnoses, cancelling out potential effects of age or sex. CONCLUSION: The economic burden incurred by RA significantly exceeds that related to OA and HBP, while differences between patients with a diagnosis of OA without HBP or a diagnosis of HBP alone were non-significant, largely owing to the influence of comorbidities.

Aged↗

Genome wide association study of rice agronomical traits and seed ionome with the NARO Open Rice Collection.

To meet the nutritional needs of the rising human population, genetic variants are necessary for the breeding of new cultivars. Rice (Oryza sativa L.) is a staple food for over half of the world's population. Here, we developed a new rice genetic resource, the NARO Open Rice Collection (NRC) with high-resolution genome data. NRC consists of 623 accessions, and approximately 200 accessions are categorized into three major subgroups, categorized as Indica, Japonica, and Aus. In this study, we performed genome-wide association studies (GWAS) for rice heading date, seed shape, and seed ionome using the NRC. Well-known genes related to heading date and seed shape were detected by GWAS using the NRC accessions. Therefore, we concluded that our new rice collection is suitable for GWAS. In addition, GWAS with each subgroup was advantageous for the detection of particular genes. Finally, we performed GWAS for seed ionome with the aim of improving the nutritional properties of rice, as essential minerals for humans, such as iron (Fe) and zinc (Zn), are not sufficient in rice seeds. Our study revealed that OsATL31, a likely ubiquitin E3 ligase, was involved in the control of Fe and Zn contents in seeds.

Oryza↗

Does an open access system properly utilize endoscopic resources?

BACKGROUND: In an effort to maintain procedure volumes and control consultation costs, many gastrointestinal endoscopists and primary care providers have implemented systems of open access endoscopy. In these systems, specialists in digestive diseases perform endoscopy without prior consultation. The purpose of this study is to determine if indications for upper endoscopic procedures requested in an open access system conform to national practice guidelines and to establish the yield of diagnostic information relevant for patient care in this system. METHODS: Procedural indications and results for 3715 upper endoscopic procedures performed in an open access system were recorded in a computer database. The practice guideline "Appropriate Use of Gastrointestinal Endoscopy" (AUGE) of the American Society for Gastrointestinal Endoscopy was used to determine appropriateness of procedural indications. RESULTS: Eighty-four percent of procedures were performed for indications listed in the AUGE, and 59% resulted in findings relevant to patient care. Specialists requested endoscopy more frequently for "approved" indications than did nonspecialists (p = .004) and more frequently had findings relevant to patient care (p < .001). Findings relevant to patient care are significantly more frequent for some indications listed in the AUGE compared to others (p < .001). CONCLUSIONS: Adherence to practice guidelines can and does occur in an open access system. Specialists request endoscopy more frequently for appropriate indications compared to nonspecialists and have a higher yield of information relevant to patient care. Further refinement and better definition of some indications within the AUGE are needed to increase the clinical utility of this document.

Endoscopy, Gastrointestinal↗

Laparoscopic versus open incisional hernia repair: a single-institution analysis of hospital resource utilization for 884 consecutive cases.

BACKGROUND: To analyze hospital resource utilization for laparoscopic vs open incisional hernia repair including the postoperative period. METHODS: Prospectively collected administrative data for incisional hernia repairs were examined. A total of 884 incisional hernia repairs were examined for trends in type of approach over time. Starting October 2001, detailed records were available, and examined for operating room (OR) time, cost data, length of stay (LOS), and 30-day postoperative hospital encounters. RESULTS: Of the total, 469 incisional hernias were approached laparoscopically (53%) and 415 open (47%). Laparoscopic repair had shorter LOS (1 +/- 0.2 days vs 2 +/- 0.6 days), longer OR time (149 +/- 4 min vs 89 +/- 4 min), higher supply costs (2,237 dollars +/- 71 dollars vs 664 dollars +/- 113 dollars), slightly lower total hospital cost (6,396 dollars +/- 477 dollars vs 7,197 dollars +/- 1,819 dollars), and slightly more postoperative hospital encounters (15% vs 13%). Use of laparoscopy increased over time (37% in 2000 vs 68% in 2004). CONCLUSIONS: Laparoscopic incisional hernia repair is becoming increasingly popular, and not at increased cost to the health care system.

Digestive System Surgical Procedures↗

A "closed" medical intensive care unit (MICU) improves resource utilization when compared with an "open" MICU.

We hypothesized that a "closed" intensive care unit (ICU) was more efficient that an "open" one. ICU admissions were retrospectively analyzed before and after ICU closure at one hospital; prospective analysis in that ICU with an open ICU nearby was done. Illness severity was gauged by the Mortality Prediction Model (MPM0). Outcomes included mortality, ICU length of stay (LOS), hospital LOS, and mechanical ventilation (MV). There were no differences in age, MPM0, and use of MV. ICU and hospital LOS were lower when "closed" (ICU LOS: prospective 6.1 versus 12.6 d, p < 0.0001; retrospective 6.1 versus 9.3 d, p < 0.05; hospital LOS: prospective 19.2 versus 33.2 d, p < 0.008; retrospective 22.2 versus 31.2 d, p < 0.02). Days on MV were lower when "closed" (prospective 2.3 versus 8.5 d, p < 0.0005; retrospective 3.3 versus 6.4 d, p < 0.05). Pooled data revealed the following: MV predicted ICU LOS; ICU organization and MPM0 predicted days on MV; MV and ICU organization predicted hospital LOS; mortality predictors were open ICU (odds ratio [OR] 1.5, p < 0.04), MPM0 (OR 1.16 for MPM0 increase 0.1, p < 0.002), and MV (OR 2.43, p < 0.0001). We conclude that patient care is more efficient with a closed ICU, and that mortality is not adversely affected.

Adolescent↗

Factors impacting functional health and resource utilization following abdominal aortic aneurysm repair by open and endovascular techniques.

We assessed the impact on patient outcomes of comorbidities and type of aneurysm repair, open vs. endovascular aortic repair (EVAR). Functional health status was measured prospectively using the Short Form 36 (SF-36) Health Survey. Length of stay (LOS) and need for postdischarge resources (nursing and rehabilitation) were compared between groups. We reviewed the records of 218 patients (126 open, 92 EVAR) who underwent intervention between 1998 and 2003. The SF-36 was completed preoperatively and at intervals ranging from 2 weeks to 1 year after intervention. To identify factors impacting outcome, univariate and multivariate analyses were performed. Overall mortality was 1.9%: 3.2% for open repair and 0% for EVAR (p = 0.13). Physical and mental health were higher during the 3 months following EVAR compared with open repair: physical function (PF) (65.2 +/- 4.1 vs. 54.0 +/- 4.1), vitality (VT) (55.5 +/- 2.5 vs. 44.9 +/- 3.4), and emotional role (ER) (74.9 +/- 5.0 vs. 51.4 +/- 6.7) (analysis of variance p < 0.05). Women following EVAR had decreased physical summary scores (PSS) (34.8 +/- 2.5 vs. 40.4 +/- 1.1, p < 0.05) compared with men postprocedure despite no difference preoperatively. Congestive heart failure (CHF) was an independent factor that negatively impacted PF, body pain (BP), and PSS. EVAR was associated with improved VT and ER. Differences among open repair and EVAR diminished over time. LOS (in days) was greater for open vs. EVAR (9.2 +/- 0.78 vs. 2.0 +/- 0.17) and in women following both open (11.8 +/- 1.5 vs. 8.0 +/- 0.9) and EVAR (3.2 +/- 0.9 vs. 1.8 +/- 0.1) procedures (p < 0.05). Factors that adversely affected LOS were open repair, age, renal insufficiency, pulmonary disease, CHF, and female gender. Following EVAR, patients were less likely to require home care or transfer to a rehabilitation facility than after open repair (14.1 vs. 36.0%, p < 0.05). Women were significantly more likely to require postdischarge care after open repair (48.7 vs. 30.1%) and EVAR (41.7 vs. 10.0%) (p < 0.05). Logistic regression identified female gender, open repair, advanced age, and pulmonary disease as independent predictors of need for postdischarge care. Those patients undergoing abdominal aortic aneurysm (AAA) repair by open technique (compared to EVAR) had significantly impaired functional health with regard to PF, VT, and ER in the first 3 months after surgery. CHF and hypertension also significantly impaired individual functional health scores. Of significance was that female gender was associated with increased LOS and increased utilization of postdischarge nursing and rehabilitation resources following both open and endovascular surgery for AAA.

Aged↗

Ethnic differences in ecological concerns: Spanish-speaking Hispanics are more concerned than others.

We postulated that environmental concern encompasses a wide range of different issues, often lumping pollution with habitat loss (or land use) and ecological resources (fish and wildlife). In this paper, we compare perceptions about a range of environmental and ecological resource issues, and explore ethnic/racial differences. We surveyed 1513 residents of New Jersey about "environmental concerns", using both general environmental questions (two questions: How serious are environmental problems in New Jersey? Are you concerned about the loss of open space?) and ecological resource questions (12 questions: e.g., how important is planting trees in your neighborhood, how concerned are you about loss of breeding and feeding habitat for fish and birds?) in New Jersey. Not all concerns were rated equally. For the ecological questions, there were no ethnic differences in concerns over preserving areas around water supplies, loss of places to hunt and fish, and loss of places for quiet walks and cycling, but there were for the other 9 ecological concerns. For eight of these nine concerns, Spanish-speaking Hispanics were more concerned than others (including English-speaking Hispanics). We divided the ecological resources into three categories: ecological services (clean water and safety), ecological resources (fish and wildlife), and recreational services. The strongest correlates of people's association with enlarging and enhancing recreational services were Spanish-speaking Hispanics, who are supportive of regulations and believe local government is not doing enough for environmental problems. People concerned about the loss of ecological resources and open space believe the federal government and the state are not doing enough for the environment, were non-Hispanic White, want continued environmental regulations, were longer-term residents, were high school graduates, and were older (45-54 years). People interested in ecological services were college-educated, non-White, not rich, females that did not trust DEP's environmental actions, and thought the state was not doing enough environmentally. There was a high correlation between general environmental concern and the ecological resource variables for the population overall, and for each ethnic group. Overall, only 39% of the subjects were very concerned about the seriousness of environmental problems in New Jersey, yet from 36% to 81% of the people were very concerned about 11 of 12 ecological issues. This indicates that people respond different to the term "environmental problems" compared to specific "ecological resource" issues. The greatest concern (81%) was for preserving areas around water supplies and cleaning up garbage in the parks, and the least concern was for the loss of places to hunt and fish (26%). Our results indicate that people distinguish between general environmental concern and ecological concerns, as well as distinguishing ecological services from ecological resources.

Asian People↗

EuroSCORE predicts intensive care unit stay and costs of open heart surgery.

BACKGROUND: This study aimed to determine whether the preoperative risk stratification model EuroSCORE predicts the different components of resource utilization in open heart surgery. METHODS: Data for all adult patients undergoing heart surgery at the University Hospital of Lund, Sweden, between 1999 and 2002 were prospectively collected. Costs were calculated for the surgery and intensive care and ward stay for each patient (excluding transplant cases and patients who died intraoperatively). Regression analysis was applied to evaluate the correlation between EuroSCORE and costs. The predictive accuracy for prolonged postoperative intensive care unit (ICU) stay was assessed by the Hosmer-Lemeshow goodness-of-fit test. The discriminatory power was evaluated by calculating the areas under receiver operating characteristics curves. RESULTS: The study included 3,404 patients. The mean cost for the surgery was 7,300 dollars, in the ICU 3,746 dollars, and in the ward 3,500 dollars. Total cost was significantly correlated with EuroSCORE, with a correlation coefficient of 0.47 (p < 0.0001); the correlation coefficient was 0.31 for the surgery cost, 0.46 for the ICU cost, and 0.11 for the ward cost. The Hosmer-Lemeshow p value for EuroSCORE prediction of more than 2 days' stay in the ICU was 0.40, indicating good accuracy. The area under the receiver operating characteristics curve was 0.78. The probability of an ICU stay exceeding 2 days was more than 50% at a EuroSCORE of 14 or more. CONCLUSIONS: In this single-institution study, the additive EuroSCORE algorithm could be used to predict ICU cost and also an ICU stay of more than 2 days after open heart surgery.

Aged↗

Ethical aspects of medical economics.

The fundamental problem of economics is how best to satisfy human needs and desires in the face of limited resources. Any benefit achieved by expending resources for one purpose is offset by an "opportunity cost": The opportunity to use those resources for other purposes is lost. Whenever resources are used to provide one medical benefit, a choice is made not to provide other benefits. The opportunity costs of medical care choices are rarely acknowledged; thus the ethical implications of such choices are rarely explicitly stated. Rationing of medical care is inevitable; how to ration our resources must be openly debated within an ethical framework. Individual physicians have an ethical obligation to avoid wasteful and unnecessary expenditures of the resources allocated to medical care. Society has an obligation to confront the ethical dilemmas implicit in health care allocation and rationing decisions. Although perhaps less painful, avoiding difficult choices is less ethical than confronting them.

Economics, Medical↗

The Bioinformatics Links Directory: a compilation of molecular biology web servers.

The Bioinformatics Links Directory is an online community resource that contains a directory of freely available tools, databases, and resources for bioinformatics and molecular biology research. The listing of the servers published in this and previous issues of Nucleic Acids Research together with other useful tools and websites represents a rich repository of resources that are openly provided to the research community using internet technologies. The 166 servers highlighted in the 2005 90002 are included in the more than 700 links to useful online resources that are currently contained within the descriptive biological categories of the Bioinformatics Links Directory. This curated listing of bioinformatics resources is available online at the Bioinformatics Links Directory web site, http://bioinformatics.ubc.ca/resources/links_directory/. A complete listing of the 2005 Nucleic Acids Research 90002 servers is available online at the Nucleic Acids web site, http://nar.oupjournals.org/, and on the Bioinformatics Links Directory web site, http://bioinformatics.ubc.ca/resources/links_directory/narweb2005/.

Computational Biology↗