242 research outputs found
Machine Learning for the New York City Power Grid
Power companies can benefit from the use of knowledge discovery methods and statistical machine learning for preventive maintenance. We introduce a general process for transforming historical electrical grid data into models that aim to predict the risk of failures for components and systems. These models can be used directly by power companies to assist with prioritization of maintenance and repair work. Specialized versions of this process are used to produce (1) feeder failure rankings, (2) cable, joint, terminator, and transformer rankings, (3) feeder Mean Time Between Failure (MTBF) estimates, and (4) manhole events vulnerability rankings. The process in its most general form can handle diverse, noisy, sources that are historical (static), semi-real-time, or real-time, incorporates state-of-the-art machine learning algorithms for prioritization (supervised ranking or MTBF), and includes an evaluation of results via cross-validation and blind test. Above and beyond the ranked lists and MTBF estimates are business management interfaces that allow the prediction capability to be integrated directly into corporate planning and decision support; such interfaces rely on several important properties of our general modeling approach: that machine learning features are meaningful to domain experts, that the processing of data is transparent, and that prediction results are accurate enough to support sound decision making. We discuss the challenges in working with historical electrical grid data that were not designed for predictive purposes. The ârawnessâ of these data contrasts with the accuracy of the statistical models that can be obtained from the process; these models are sufficiently accurate to assist in maintaining New York City's electrical grid
Perspective:Moving Toward Desirable Linoleic Acid Content in Infant Formula
Infant formula should provide the appropriate nutrients and adequate energy to facilitate healthy infant growth and development. If conclusive data on quantitative nutrient requirements are not available, the composition of human milk (HM) can provide some initial guidance on the infant formula composition. This paper provides a narrative review of the current knowledge, unresolved questions, and future research needs in the area of HM fatty acid (FA) composition, with a particular focus on exploring appropriate intake levels of the essential FA linoleic acid (LA) in infant formula. The paper highlights a clear gap in clinical evidence as to the impact of LA levels in HM or formula on infant outcomes, such as growth, development, and long-term health. The available preclinical information suggests potential disadvantages of high LA intake in the early postnatal period. We recommend performing well-designed clinical intervention trials to create clarity on optimal levels of LA to achieve positive impacts on both short-term growth and development and long-term functional health outcomes
Acute cholecystitis in high risk surgical patients: percutaneous cholecystostomy versus laparoscopic cholecystectomy (CHOCOLATE trial): Study protocol for a randomized controlled trial
<p>Abstract</p> <p>Background</p> <p>Laparoscopic cholecystectomy in acute calculous cholecystitis in high risk patients can lead to significant morbidity and mortality. Percutaneous cholecystostomy may be an alternative treatment option but the current literature does not provide the surgical community with evidence based advice.</p> <p>Methods/Design</p> <p>The CHOCOLATE trial is a randomised controlled, parallel-group, superiority multicenter trial. High risk patients, defined as APACHE-II score 7-14, with acute calculous cholecystitis will be randomised to laparoscopic cholecystectomy or percutaneous cholecystostomy. During a two year period 284 patients will be enrolled from 30 high volume teaching hospitals. The primary endpoint is a composite endpoint of major complications within three months following randomization and need for re-intervention and mortality during the follow-up period of one year. Secondary endpoints include all other complications, duration of hospital admission, difficulty of procedures and total costs.</p> <p>Discussion</p> <p>The CHOCOLATE trial is designed to provide the surgical community with an evidence based guideline in the treatment of acute calculous cholecystitis in high risk patients.</p> <p>Trial Registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2666">NTR2666</a></p
Attribution of the heavy rainfall events leading to severe flooding in Western Europe during July 2021
In July 2021 extreme rainfall across Western Europe caused severe flooding and substantial impacts, including over 200 fatalities and extensive infrastructure damage within Germany and the Benelux countries. After the event, a hydrological assessment and a probabilistic event attribution analysis of rainfall data were initiated and complemented by discussing the vulnerability and exposure context. The global mean surface temperature (GMST) served as a covariate in a generalised extreme value distribution fitted to observational and model data, exploiting the dependence on GMST to estimate how anthropogenic climate change affects the likelihood and severity of extreme events. Rainfall accumulations in Ahr/Erft and the Belgian Meuse catchment vastly exceeded previous observed records. In regions of that limited size the robust estimation of return values and the detection and attribution of rainfall trends are challenging. However, for the larger Western European region it was found that, under current climate conditions, on average one rainfall event of this magnitude can be expected every 400 years at any given location. Consequently, within the entire region, events of similar magnitude are expected to occur more frequently than once in 400 years. Anthropogenic climate change has already increased the intensity of the maximum 1-day rainfall event in the summer season by 3â19Â %. The likelihood of such an event to occur today compared to a 1.2Â C cooler climate has increased by a factor of 1.2â9. Models indicate that intensity and frequency of such events will further increase with future global warming. While attribution of small-scale events remains challenging, this study shows that there is a robust increase in the likelihood and severity of rainfall events such as the ones causing extreme impacts in July 2021 when considering a larger region
Differences in SMA-like polymer architecture dictate the conformational changes exhibited by the membrane protein rhodopsin encapsulated in lipid nano-particles
Membrane proteins are of fundamental importance to cellular processes and nano-encapsulation strategies that preserve their native lipid bilayer environment are particularly attractive for studying and exploiting these proteins. Poly(styrene-co-maleic acid) (SMA) and related polymers poly(styrene-co-(N-(3-NâČ,NâČ-dimethylaminopropyl)maleimide)) (SMI) and poly(diisobutylene-alt-maleic acid) (DIBMA) have revolutionised the study of membrane proteins by spontaneously solubilising membrane proteins direct from cell membranes within nanoscale discs of native bilayer called SMA lipid particles (SMALPs), SMILPs and DIBMALPs respectively. This systematic study shows for the first time, that conformational changes of the encapsulated protein are dictated by the solubilising polymer. The photoactivation pathway of rhodopsin (Rho), a G-protein-coupled receptor (GPCR), comprises structurally-defined intermediates with characteristic absorbance spectra that revealed conformational restrictions with styrene-containing SMA and SMI, so that photoactivation proceeded only as far as metarhodopsin-I, absorbing at 478 nm, in a SMALP or SMILP. In contrast, full attainment of metarhodopsin-II, absorbing at 382 nm, was observed in a DIBMALP. Consequently, different intermediate states of Rho could be generated readily by simply employing different SMA-like polymers. Dynamic light-scattering and analytical ultracentrifugation revealed differences in size and thermostability between SMALP, SMILP and DIBMALP. Moreover, encapsulated Rho exhibited different stability in a SMALP, SMILP or DIBMALP. Overall, we establish that SMA, SMI and DIBMA constitute a âtoolkitâ of solubilising polymers, so that selection of the appropriate solubilising polymer provides a spectrum of useful attributes for studying membrane proteins
Attribution of the heavy rainfall events leading to severe flooding in Western Europe during July 2021
In July 2021 extreme rainfall across Western Europe caused severe flooding and substantial impacts, including over 200 fatalities and extensive infrastructure damage within Germany and the Benelux countries. After the event, a hydrological assessment and a probabilistic event attribution analysis of rainfall data were initiated and complemented by discussing the vulnerability and exposure context. The global mean surface temperature (GMST) served as a covariate in a generalised extreme value distribution fitted to observational and model data, exploiting the dependence on GMST to estimate how anthropogenic climate change affects the likelihood and severity of extreme events. Rainfall accumulations in Ahr/Erft and the Belgian Meuse catchment vastly exceeded previous observed records. In regions of that limited size the robust estimation of return values and the detection and attribution of rainfall trends are challenging. However, for the larger Western European region it was found that, under current climate conditions, on average one rainfall event of this magnitude can be expected every 400 years at any given location. Consequently, within the entire region, events of similar magnitude are expected to occur more frequently than once in 400 years. Anthropogenic climate change has already increased the intensity of the maximum 1-day rainfall event in the summer season by 3â19Â %. The likelihood of such an event to occur today compared to a 1.2 â C cooler climate has increased by a factor of 1.2â9. Models indicate that intensity and frequency of such events will further increase with future global warming. While attribution of small-scale events remains challenging, this study shows that there is a robust increase in the likelihood and severity of rainfall events such as the ones causing extreme impacts in July 2021 when considering a larger region
Folate Receptor-Beta Has Limited Value for Fluorescent Imaging in Ovarian, Breast and Colorectal Cancer
Aims Tumor-specific targeted imaging is rapidly evolving in cancer diagnosis. The folate receptor alpha (FR-alpha) has already been identified as a suitable target for cancer therapy and imaging. FR-alpha is present on similar to 40% of human cancers. FR-beta is known to be expressed on several hematologic malignancies and on activated macrophages, but little is known about FR-beta expression in solid tumors. Additional or simultaneous expression of FR-beta could help extend the indications for folate-based drugs and imaging agents. In this study, the expression pattern of FR-beta is evaluated in ovarian, breast and colorectal cancer. Methods FR-beta expression was analyzed by semi-quantitative scoring of immunohistochemical staining on tissue microarrays (TMAs) of 339 ovarian cancer patients, 418 breast cancer patients, on 20 slides of colorectal cancer samples and on 25 samples of diverticulitis. Results FR-beta expression was seen in 21% of ovarian cancer samples, 9% of breast cancer samples, and 55% of colorectal cancer samples. Expression was weak or moderate. Of the diverticulitis samples, 80% were positive for FR-beta expression in macrophages. FR-beta status neither correlated to known disease-related variables, nor showed association with overall survival and progression free survival in ovarian and breast cancer. In breast cancer, negative axillary status was significantly correlated to FR-beta expression (p=0.022). Conclusions FR-beta expression was low or absent in the majority of ovarian, breast and colorectal tumor samples. From the present study we conclude that the low FR-beta expression in ovarian and breast tumor tissue indicates limited practical use of this receptor in diagnostic imaging and therapeutic purposes. Due to weak expression, FR-beta is not regarded as a suitable target in colorectal cancer
Beyond gene-disease validity: capturing structured data on inheritance, allelic requirement, disease-relevant variant classes, and disease mechanism for inherited cardiac conditions
Background:
As the availability of genomic testing grows, variant interpretation will increasingly be performed by genomic generalists, rather than domain-specific experts. Demand is rising for laboratories to accurately classify variants in inherited cardiac condition (ICC) genes, including secondary findings.
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Methods:
We analyse evidence for inheritance patterns, allelic requirement, disease mechanism and disease-relevant variant classes for 65 ClinGen-curated ICC gene-disease pairs. We present this information for the first time in a structured dataset, CardiacG2P, and assess application in genomic variant filtering.
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Results:
For 36/65 gene-disease pairs, loss of function is not an established disease mechanism, and protein truncating variants are not known to be pathogenic. Using the CardiacG2P dataset as an initial variant filter allows for efficient variant prioritisation whilst maintaining a high sensitivity for retaining pathogenic variants compared with two other variant filtering approaches.
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Conclusions:
Access to evidence-based structured data representing disease mechanism and allelic requirement aids variant filtering and analysis and is a pre-requisite for scalable genomic testing
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