The genetics of complex disease produce alterations in the molecular interactions of cellular pathways whose collective effect may become clear through the organized structure of molecular networks. ...To characterize molecular systems associated with late-onset Alzheimer’s disease (LOAD), we constructed gene-regulatory networks in 1,647 postmortem brain tissues from LOAD patients and nondemented subjects, and we demonstrate that LOAD reconfigures specific portions of the molecular interaction structure. Through an integrative network-based approach, we rank-ordered these network structures for relevance to LOAD pathology, highlighting an immune- and microglia-specific module that is dominated by genes involved in pathogen phagocytosis, contains TYROBP as a key regulator, and is upregulated in LOAD. Mouse microglia cells overexpressing intact or truncated TYROBP revealed expression changes that significantly overlapped the human brain TYROBP network. Thus the causal network structure is a useful predictor of response to gene perturbations and presents a framework to test models of disease mechanisms underlying LOAD.
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•Systems approach to LOAD based on large-scale human brain-tissue sampling•Molecular networks show strong remodeling effect in LOAD brains•Integrative network-based analysis implicates the immune/microglia network in LOAD•TYROBP implicated as key causal regulator within the immune/microglia module
An integrated systems approach leverages transcriptome data from postmortem brains of late-onset Alzheimer’s disease patients to identify key nodes that drive dysregulated or rewired networks in the disease state.
Purpose
While the use of transthoracic echocardiography (TTE) in the ICU is rapidly expanding, the contribution of TTE to altering patient outcomes among ICU patients with sepsis has not been ...examined. This study was designed to examine the association of TTE with 28-day mortality specifically in that population.
Methods and results
The MIMIC-III database was employed to identify patients with sepsis who had and had not received TTE. The statistical approaches utilized included multivariate regression, propensity score analysis, doubly robust estimation, the gradient boosted model, and an inverse probability-weighting model to ensure the robustness of our findings. Significant benefit in terms of 28-day mortality was observed among the TTE patients compared to the control (no TTE) group (odds ratio = 0.78, 95% CI 0.68–0.90,
p
< 0.001). The amount of fluid administered (2.5 vs. 2.1 L on day 1,
p
< 0.001), use of dobutamine (2% vs. 1%,
p
= 0.007), and the maximum dose of norepinephrine (1.4 vs. 1 mg/min,
p
= 0.001) were significantly higher for the TTE patients. Importantly, the TTE patients were weaned off vasopressors more quickly than those in the no TTE group (vasopressor-free days on day 28 of 21 vs. 19,
p
= 0.004).
Conclusion
In a general population of critically ill patients with sepsis, use of TTE is associated with an improvement in 28-day mortality.
Summer mortality (SM) in greenlip abalone (Haliotis laevigata Donovan) heavily affects productivity of land-based abalone farms in Southern Australia. It has been associated with conditions of high ...water temperature (>23°C), low dissolved oxygen levels, and a range of other stressful factors in the culture water during summer months. This study aimed to alleviate mortality experienced by abalone at high water temperatures (26°C), by dietary intervention using grape seed extract (GSE) and dried Ulva lactuca Linnaeus, two products which contain antioxidative and bioactive compounds. These products were formulated into a commercial abalone diet at levels of 5 and 30%. The diets were fed to 3-year-old greenlip abalone (26.8g; 57.9mm) at a water temperature of 22 or 26°C for 38days. No mortalities were observed at 22°C. Compared to the unaltered commercial diet, both GSE and dried U. lactuca additive diets significantly increased the survival of abalone at the 26°C water temperature (P<0.05). GSE addition also significantly increased serum superoxide dismutase activity, feed intake, and meal acceptance of the abalone (P<0.05). These results demonstrate the potential for GSE or dried U. lactuca to act as dietary additives to reduce mortality and improve productivity on abalone farms subjected to high summer water temperatures.
•Grape seed extract reduces mortality of greenlip abalone at high water temperatures.•Dried Ulva lactuca also improved survival at high temperatures.•Grape seed extract was more efficient than dried Ulva lactuca.•Information to be used to reduce mortality at high summer water temperatures on-farm
Mortuary landscapes of North Africa Stirling, Lea; Stone, David, L
Mortuary landscapes of North Africa,
2007, 20070317, 2007, 2007-01-01, 2007-12-15, Letnik:
43, 43.
eBook
Unique in both scope and perspective, this volume will prove invaluable to a cross-section of archaeological scholars.
This book uses manorial account rolls innovatively to reconstruct the economic mentalities of medieval farmers and, by so doing, argues that they have been unfairly stereotyped. It overturns the ...traditional view of medieval countrymen as economically backward and instead reveals that agricultural decision-making was as rational in the 14th and 15th centuries as in modern times. It investigates agricultural mentalities first in a detailed case study of the exceptionally well-documented demesne farm of Wisbech Barton, analysing the sale and consumption of produce, cereal-cropping strategies, crop rotations, the use of agrarian techniques, and livestock husbandry in four periods between 1313 and 1429. The last third of the book then tests the findings of this case study across medieval England as a whole. The book argues that human action shaped the course of the rural economy to a much greater extent than has hitherto been appreciated, and challenges the commonly held view that the medieval period was dominated by ecological and economic crises. In particular, it argues that rational decision-making rather than soil exhaustion or climatic change lay behind declining arable and pastoral yields at this time, and that the change in demesne management from direct cultivation to leasing during the later Middle Ages was partly the result of a managerial crisis. Although focused chiefly on well-documented farms of great landlords, the book also has crucial implications for our understanding of medieval peasant farming, not least the yield of their land, which may well have been significantly higher than is generally assumed.
OBJECTIVES:To evaluate the relative validity of criteria for the identification of sepsis in an ICU database.
DESIGN:Retrospective cohort study of adult ICU admissions from 2008 to 2012.
...SETTING:Tertiary teaching hospital in Boston, MA.
PATIENTS:Initial admission of all adult patients to noncardiac surgical ICUs.
INTERVENTIONS:Comparison of five different algorithms for retrospectively identifying sepsis, including the Sepsis-3 criteria.
MEASUREMENTS AND MAIN RESULTS:11,791 of 23,620 ICU admissions (49.9%) met criteria for the study. Within this subgroup, 59.9% were suspected of infection on ICU admission, 75.2% of admissions had Sequential Organ Failure Assessment greater than or equal to 2, and 49.1% had both suspicion of infection and Sequential Organ Failure Assessment greater than or equal to 2 thereby meeting the Sepsis-3 criteria. The area under the receiver operator characteristic of Sequential Organ Failure Assessment (0.74) for hospital mortality was consistent with previous studies of the Sepsis-3 criteria. The Centers for Disease Control and Prevention, Angus, Martin, Centers for Medicare & Medicaid Services, and explicit coding methods for identifying sepsis revealed respective sepsis incidences of 31.9%, 28.6%, 14.7%, 11.0%, and 9.0%. In-hospital mortality increased with decreasing cohort size, ranging from 30.1% (explicit codes) to 14.5% (Sepsis-3 criteria). Agreement among the criteria was acceptable (Cronbach’s alpha, 0.40–0.62).
CONCLUSIONS:The new organ dysfunction-based Sepsis-3 criteria have been proposed as a clinical method for identifying sepsis. These criteria identified a larger, less severely ill cohort than that identified by previously used administrative definitions. The Sepsis-3 criteria have several advantages over prior methods, including less susceptibility to coding practices changes, provision of temporal context, and possession of high construct validity. However, the Sepsis-3 criteria also present new challenges, especially when calculated retrospectively. Future studies on sepsis should recognize the differences in outcome incidence among identification methods and contextualize their findings according to the different cohorts identified.
Abstract
Objective
Lack of reproducibility in medical studies is a barrier to the generation of a robust knowledge base to support clinical decision-making. In this paper we outline the Medical ...Information Mart for Intensive Care (MIMIC) Code Repository, a centralized code base for generating reproducible studies on an openly available critical care dataset.
Materials and Methods
Code is provided to load the data into a relational structure, create extractions of the data, and reproduce entire analysis plans including research studies.
Results
Concepts extracted include severity of illness scores, comorbid status, administrative definitions of sepsis, physiologic criteria for sepsis, organ failure scores, treatment administration, and more. Executable documents are used for tutorials and reproduce published studies end-to-end, providing a template for future researchers to replicate. The repository’s issue tracker enables community discussion about the data and concepts, allowing users to collaboratively improve the resource.
Discussion
The centralized repository provides a platform for users of the data to interact directly with the data generators, facilitating greater understanding of the data. It also provides a location for the community to collaborate on necessary concepts for research progress and share them with a larger audience. Consistent application of the same code for underlying concepts is a key step in ensuring that research studies on the MIMIC database are comparable and reproducible.
Conclusion
By providing open source code alongside the freely accessible MIMIC-III database, we enable end-to-end reproducible analysis of electronic health records.
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2015 and co-published as a series in Critical Care. Other articles in the series can be ...found online at http://ccforum.com/series/annualupdate2015. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.
Open repair effectively prevents rupture for patients with abdominal aortic aneurysm (AAA) and is commonly studied as a metric reflecting hospital and surgeon expertise in cardiovascular care. ...However, given recent advances in endovascular aneurysm repair (EVAR), such as branched-fenestrated EVAR, it is unknown how commonly open surgical repair is still used in everyday practice.
We analyzed trends in open AAA repair, EVAR, and branched-fenestrated EVAR for AAA in Medicare beneficiaries from 2003 to 2013. We used Medicare Part B claims to ascertain counts of these repair types annually during the study period. We assessed regional and national trends in characteristics of the patients and procedure volume.
Between 2003 and 2013, the total number of AAA repairs performed in fee-for-service Medicare patients declined by 26% from 31,582 to 23,421 (P < .001), after a peak number of 32,540 was performed in 2005 (28% decline since 2005). The number of open AAA repairs steadily declined by a total of 76%, from 20,533 in 2003 to 4916 in 2013 (P < .001). Whereas the number of EVARs increased from 11,049 in 2003 to 19,247 in 2011 (P < .001), it has since declined a total of 15% to only 16,362 repairs in 2013 (P < .001). After its introduction in 2011, the number of branched-fenestrated EVAR cases continuously rose from 335 procedures in 2011 to 2143 procedures in 2013 (P < .001). By 2013, virtually all hospital referral regions in the United States had rates of open AAA repair that would have been in the lowest quintile of volume in 2003.
The number of open AAA repairs fell by nearly 80% during the last decade, whereas traditional EVAR declined slightly and branched-fenestrated EVAR rapidly disseminated into national practice. These results suggest that open AAA repair is now performed too infrequently to be used as a metric in the assessment of hospital and surgeon quality in cardiovascular care. Furthermore, surgical training paradigms will need to reflect the changing dynamics necessary to ensure that surgeons and interventionists can safely perform these high-risk surgical procedures.
The mucosal surfaces and associated microbiota of fish are an important primary barrier and provide the first line of defense against potential pathogens. An understanding of the skin and gill ...microbial assemblages and the factors which drive their composition may provide useful insights into the broad dynamics of fish host-microbial relationships, and may reveal underlying changes in health status. This is particularly pertinent to cultivated systems whereby various stressors may led to conditions (like enteritis) which impinge on productivity. As an economically important species, we assessed whether the outer-surface bacterial communities reflect a change in gut health status of cultivated Yellowtail Kingfish (
). Active bacterial assemblages were surveyed from RNA extracts from swabs of the skin and gills by constructing Illumina 16S rRNA gene amplicon libraries. Proteobacteria and Bacteroidetes were predominant in both the skin and gills, with enrichment of key β-proteobacteria in the gills (Nitrosomonadales and Ferrovales). Fish exhibiting early stage chronic lymphocytic enteritis comprised markedly different global bacterial assemblages compared to those deemed healthy and exhibiting late stages of the disease. This corresponded to an overall loss of diversity and enrichment of Proteobacteria and Actinobacteria, particularly in the gills. In contrast, bacterial assemblages of fish with late stage enteritis were generally similar to those of healthy individuals, though with some distinct taxa. In conclusion, gut health status is an important factor which defines the skin and gill bacterial assemblages of fish and likely reflects changes in immune states and barrier systems during the early onset of conditions like enteritis. This study represents the first to investigate the microbiota of the outer mucosal surfaces of fish in response to underlying chronic gut enteritis, revealing potential biomarkers for assessing fish health in commercial aquaculture systems.
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