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PubMed2001

The eICU: it's not just telemedicine.

Intensive care units (ICUs) are major sites for medical errors and adverse events. Suboptimal outcomes reflect a widespread failure to implement care delivery systems that successfully address the complexity of modern ICUs. Whereas other industries have used information technologies to fundamentally improve operating efficiency and enhance safety, medicine has been slow to implement such strategies. Most ICUs do not even track performance; fewer still have the capability to examine clinical data and use this information to guide quality improvement initiatives. This article describes a technology-enabled care model (electronic ICU, or eICU) that represents a new paradigm for delivery of critical care services. A major component of the model is the use of telemedicine to leverage clinical expertise and facilitate a round-the-clock proactive care by intensivist-led teams of ICU caregivers. Novel data presentation formats, computerized decision support, and smart alarms are used to enhance efficiency, increase effectiveness, and standardize clinical and operating processes. In addition, the technology infrastructure facilitates performance improvement by providing an automated means to measure outcomes, track performance, and monitor resource utilization. The program is designed to support the multidisciplinary intensivist-led team model and incorporates comprehensive ICU re-engineering efforts to change practice behavior. Although this model can transform ICUs into centers of excellence, success will hinge on hospitals accepting the underlying value proposition and physicians being willing to change established practices.

Hospitalists↗

PubMed1992

Short-term projections of AIDS cases in Mexico.

We attempt to analyze and predict the behavior of the AIDS epidemic in Mexico. The reporting delay is corrected by using a cluster analysis, and the corrected data are used to make short-term projections by extrapolation, by fitting linear and log-linear models, and by back-calculation. The incubation period is assumed to have a Weibull distribution, and step functions are used for the infection functions. Most of the methods predict a mean of 25,000 accumulated cases by the end of 1993, and a comparison of the predictions with actual data up to November 1990 shows good agreement in all cases except the log-transformation linear model. The data for 1990 also show the reporting delay correction to be adequate in most cases.

Acquired Immunodeficiency Syndrome↗

PubMed2006

A process model of healing and personal transformation in persons with chronic skin wounds.

Utilizing Newman's research as praxis process, this research examined the patterns of those living with chronic skin wounds. Ten men and 8 women, primarily of retirement age and living with chronic skin wounds for a year or more, reflected upon important relationships and life events during two in-depth interviews and a self-expressive drawing. Emerging from each participant's pattern was the link among human development, expanding consciousness, and processing a serious physical threat. Considering data across participants, five themes emerged from the data with evolution of a process model of wholistic healing that has implications for advanced nursing practice.

Chronic Disease↗

PubMed1985

Gene amplification in Aspergillus nidulans by transformation with vectors containing the amdS gene.

Conidial protoplasts of an A. nidulans amdS deletion strain (MH1277) have been transformed to the AmdS+ phenotype with a plasmid carrying the wild type gene (p3SR2). Optimalisation of transformation and plating conditions now has resulted in frequencies of 300-400 transformants per microgram of DNA. Analysis of DNA from AmdS+ transformants of MH1277 showed that transformation had occurred by integration of vector DNA sequences into the genome. In virtually all these transformants multiple copies of the vector were present in a tandemly repeated fashion, not preferentially at the resident, partially deleted amdS gene. It is suggested that the observed integration phenomena are dependent on the genetic background of the A. nidulans strain, used for transformation. A model to explain the tandem type of integration is proposed.

Aspergillus nidulans↗

PubMed1986

A perceptual model of vowel recognition based on the auditory representation of American English vowels.

A quantitative perceptual model of human vowel recognition based upon psychoacoustic and speech perception data is described. At an intermediate auditory stage of processing, the specific bark difference level of the model represents the pattern of peripheral auditory excitation as the distance in critical bands (barks) between neighboring formants and between the fundamental frequency (F0) and first formant (F1). At a higher, phonetic stage of processing, represented by the critical bark difference level of the model, the transformed vowels may be dichotomously classified based on whether the difference between formants in each dimension falls within or exceeds the critical distance of 3 bark for the spectral center of gravity effect [Chistovich et al., Hear. Res. 1, 185-195 (1979)]. Vowel transformations and classifications correspond well to several major phonetic dimensions and features by which vowels are perceived and traditionally classified. The F1-F0 dimension represents vowel height, and high vowels have F1-F0 differences within 3 bark. The F3-F2 dimension corresponds to vowel place of articulation, and front vowels have F3-F2 differences of less than 3 bark. As an inherent, speaker-independent normalization procedure, the model provides excellent vowel clustering while it greatly reduces between-speaker variability. It offers robust normalization through feature classification because gross binary categorization allows for considerable acoustic variability. There was generally less formant and bark difference variability for closely spaced formants than for widely spaced formants. These findings agree with independently observed perceptual results and support Stevens' quantal theory of vowel production and perceptual constraints on production predicted from the critical bark difference level of the model.

Adult↗

PubMed2006

Prognostic value of plasma chromogranin A levels in patients with complicated myocardial infarction.

BACKGROUND: Chromogranin A is widely distributed throughout the neuroendocrine system and may, because of its long in vivo and in vitro half-life, be an attractive candidate for assessment of overall neuroendocrine activity. Recently, increased plasma levels of chromogranin A have been found in patients with chronic heart failure and related to the severity of symptoms and prognosis. The objective of the current study was to assess the prognostic value of chromogranin A levels after complicated myocardial infarction. METHODS: We assessed the association between plasma chromogranin A levels obtained in the hospitalization phase and time to hospitalization for heart failure or death in 217 patients with complicated myocardial infarction included in the OPTIMAAL trial. RESULTS: During a median follow-up time of 1017 days, there were 44 first events (30 deaths and 14 hospitalizations for congestive heart failure). Logarithmically transformed chromogranin A (P < .001) and N-terminal pro-B-type natriuretic peptide (P = .001), patient age (P < .001), estimated creatinine clearance (P < .001), a history of myocardial infarction or angina (P = .001), and diabetes mellitus (P = .011), using univariable Cox proportional hazards regression, were significantly associated with outcome, whereas sex, randomization status, history of hypertension, C-reactive protein, and the presence of inhospital heart failure were not. In a multivariable model, logarithmically transformed chromogranin A (P = .002), patient age (P < .0001), history of diabetes (P = .004), and male sex (P = .021) were independently predictive of outcome. CONCLUSION: Chromogranin A is a strong and independent prognostic indicator in patients with complicated myocardial infarction.

Aged↗

PubMed1995

Modelling of microbial activity and prediction of shelf life for packed fresh fish.

Prediction of shelf life based on growth of specific spoilage organisms (SSO) in model substrates was studied. The effect of CO2 on the growth kinetics for Photobacterium phosphoreum and Shewanella putrefaciens was quantified and modelled. Results showed that microbial spoilage of packed cod stored with various concentrations of CO2 was accurately predicted from the effect of CO2 on P. phosphoreum grown in model substrates. The short shelf life extensions previously reported for packed cod therefore can be explained by the high CO2 resistance of this Gram negative organism. S. putrefaciens was very sensitive to CO2 and growth rates could not be related to the shelf life of packed cod. Growth curves without lag phases were found for all concentrations of CO2 and for both the microorganisms studied. For the fitting of these growth curves the log-transformed Logistic models were selected after comparison with the 'modified Gompertz' models and with the model of Baranyi et al. (1993). The effect of CO2 on mu max was well described by a 2 parameter square root model. Validation of kinetic models by comparison of shelf life predictions with shelf life determined by sensory evaluations in product experiments was preferred for comparison of microbial growth rates determined in product and model system experiments. Kinetic modelling was found to be valuable for both evaluation and prediction of microbial fish spoilage and an iterative approach for development of kinetic shelf life models was suggested.

Animals↗

PubMed2004

Therapeutic applications of chymase inhibitors in cardiovascular diseases and fibrosis.

Chymase activates not only angiotensin I to angiotensin II but also latent transforming growth factor-beta-binding protein to transforming growth factor-beta. In dog grafted veins, chymase activity and angiotensin II concentration along with vascular proliferation were significantly increased, while they were significantly suppressed by a chymase inhibitor. After balloon injury in dog arteries, chymase activity was significantly increased in the injured artery, and a chymase inhibitor and an angiotensin AT(1) receptor antagonist were effective in preventing the vascular proliferation, but an angiotensin-converting enzyme inhibitor was ineffective. In fibrotic models, the tissue fibrosis was reduced by chymase inhibitors. In adhesion models, the transforming growth factor-beta concentration and adhesion formation were suppressed by chymase inhibitors. Therefore, chymase inhibitors may be useful for preventing cardiovascular diseases and fibrosis via inhibition of angiotensin II formation and transforming growth factor-beta activation.

Animals↗

PubMed2000

Nurse executive transformational leadership found in participative organizations.

OBJECTIVE: The study examined a national sample of 396 randomly selected hospital nurse executives to explore transformational leadership, stage of power, and organizational climate. BACKGROUND: Results from a few nurse executive studies have found nurse executives were transformational leaders. As executives were more transformational, they achieved better staff satisfaction and higher work group effectiveness. This study integrates Bass' transformational leadership model with Hagberg's power stage theory and Likert's organizational climate theory. METHODS: Nurse executives (396) and staff reporting to them (1,115) rated the nurse executives' leadership style, staff extra effort, staff satisfaction, and work group effectiveness using Bass and Avolio's Multifactor Leadership Questionnaire. Executives' bosses (360) rated executive work group effectiveness. Executives completed Hagberg's Personal Power Profile and ranked their organizational climate using Likert's Profile of Organizational Characteristics. RESULTS: Nurse executives used transformational leadership fairly often; achieved fairly satisfied staff levels; were very effective according to bosses; were most likely at stage 3 (power by achievement) or stage 4 (power by reflection); and rated their hospital as a Likert System 3 Consultative Organization. Staff satisfaction and work group effectiveness decreased as nurse executives were more transactional. Higher transformational scores tended to occur with higher educational degrees and within more participative organizations. CONCLUSIONS: Transformational qualities can be enhanced by further education, by achieving higher power stages, and by being within more participative organizations.

Adult↗

PubMed2025

Deep learning guided programmable design of Escherichia coli core promoters from sequence architecture to strength control.

Core promoters are essential regulatory elements that control transcription initiation, but accurately predicting and designing their strength remains challenging due to complex sequence-function relationships and the limited generalizability of existing AI-based approaches. To address this, we developed a modular platform integrating rational library design, predictive modelling, and generative optimization into a closed-loop workflow for end-to-end core promoter engineering. Conserved and spacer region of core promoters exert distinct effects on transcriptional strength, with the former driving large-scale variation and the latter enabling finer gradation. Based on this insight, Mutation-Barcoding-Reverse Sequencing approach was used and constructed a synthetic promoter library comprising 112 955 variants with minimal redundancy and a 16 226-fold expression range. A Transformer-based model trained on this dataset achieved a Pearson correlation of 0.87 with experimentally measured promoter strengths. When combined with a conditional diffusion model, the system enabled de novo generation of promoter sequences with defined strengths, achieving a design-to-measurement correlation of 0.95 and maintaining high accuracy (R = 0.93) across varied sequence contexts. The designed promoters consistently preserved their intended strength gradients, demonstrating robust plug-and-play functionality. This work establishes a scalable and extensible platform (www.yudenglab.com) for deep learning-guided programmable design of Escherichia coli core promoters, enabling precise transcriptional control.

Promoter Regions, Genetic↗

PubMed1992

[PHO2 and GCN4 transcription activators in the regulation of Saccharomyces cerevisiae acid phosphatase synthesis].

The possibility of substitution of the PHO2 activator protein by GCN4 protein in transcriptional regulation of acid phosphatase genes PHO5 and PHO11 was demonstrated in the yeast Saccharomyces cerevisiae. We observed the increase in acid phosphatase synthesis in the case of gcn4-delta 1 pho2-delta 1 mutant transformed with YCp88 (GCN4-wt) plasmid in comparison with that in nontransformed cells. The mode of repression of acid phosphatase synthesis in two types of transformants gcn4-delta 1 pho2-delta 1 (GCN4-wt) and gcn4-delta 1 pho2-delta 1 (PHO2-wt) was studied. It wat demonstrated that repression of acid phosphatase synthesis in the first type of transformants took place at lower concentration of Pi than was necessary for the second type of transformants. The model of interactions between the GCN4 activator protein and PHO regulatory factors is proposed.

Acid Phosphatase↗

PubMed2002

A study and comparative analysis of managerial and leadership effectiveness in the National Health Service: an empirical factor analytic study within an NHS Trust hospital.

The research described in this article was concerned primarily with identifying the criteria of managerial/leadership effectiveness applying at the middle and front line levels of management within an NHS Trust Hospital using critical incident technique and factor analysis methods. The findings suggest that the self-perceptions of managers and the perceptions of superiors and subordinates are very similar, and only differ on a limited number of criteria. This challenges the 'perspective-specific' models of managerial effectiveness advocated by some researchers. The results are compared against those from a near identical study carried out by the author within one part of the British Civil Service, and the results from a different but comparable factor analytic study carried out by other researchers elsewhere in the NHS. The results suggest the existence of generalized criteria of managerial effectiveness, which lend considerable support to the notion of the 'universally effective manager'. This challenges the 'contingent models' of managerial effectiveness advocated by various expert commentators. In addition, the research supports the new model of transformational leadership offered by Alimo-Metcalfe and Alban-Metcalfe for application within both the NHS and local government, and adds to the empirical base supporting the current drive towards evidence-based practice in management within the healthcare sector.

Efficiency, Organizational↗

PubMed2003

Hierarchical model of gene regulation by transforming growth factor beta.

Transforming growth factor betas (TGF-betas) regulate key aspects of embryonic development and major human diseases. Although Smad2, Smad3, and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases (MAPKs) have been proposed as key mediators in TGF-beta signaling, their functional specificities and interactivity in controlling transcriptional programs in different cell types and (patho)physiological contexts are not known. We investigated expression profiles of genes controlled by TGF-beta in fibroblasts with ablations of Smad2, Smad3, and ERK MAPK. Our results suggest that Smad3 is the essential mediator of TGF-beta signaling and directly activates genes encoding regulators of transcription and signal transducers through Smad3/Smad4 DNA-binding motif repeats that are characteristic for immediate-early target genes of TGF-beta but absent in intermediate target genes. In contrast, Smad2 and ERK predominantly transmodulated regulation of both immediate-early and intermediate genes by TGF-beta/Smad3. These results suggest a previously uncharacterized hierarchical model of gene regulation by TGF-beta in which TGF-beta causes direct activation by Smad3 of cascades of regulators of transcription and signaling that are transmodulated by Smad2 and/or ERK.

Animals↗

PubMed1997

Investigation of aging in polymer networks by T1 rho material property NMR imaging.

Material property (MAP) imaging was found to be a promising method for the investigation of aging processes in elastomer materials. Based on conventional parameter-selective imaging, MAP imaging directly reveals the properties of the material by use of a theoretical description to relate the measured nuclear magnetic resonance data--in this investigation, T1 rho values--with the properties of the material. Following this concept, T1 rho images with different strengths of lock amplitude have been acquired for a rubber sample consisting of four pieces of natural rubber that were oxidatively aged under different conditions. The data were analyzed using a defect-diffusion model and transformed into images of those material parameters, which were found to be suitable for the characterization of the aging process. Images correlating with the crosslink density and the power law of T1 rho dispersion were obtained indicating the degree of aging.

Algorithms↗

PubMedDate not supplied

[Analysis of the prevalence of distichiasis in the dog breed Elo].

The Elo is a recently established dog breed in which the eye anomaly distichiasis has been frequently observed. Out of a total of 234 Elo dogs ophthalmologically examined over four years, 27.8% of the dogs showed between 1 and 31 distichia. There were twice as many distichia in the upper than in the lower eyelid. Litter size, the number of examinations of Elo dogs per ophthalmologist and the proportion of genes of the Eurasian dog had a significant influence on the prevalence of distichiasis. The error probability for the inbreeding coefficient and the proportion of genes of the Old English Sheepdog were just above the significance limit of p = 0.05. No significance was found for the remaining effects. Heritability for distichiasis was estimated using a linear animal model. After transformation of the linear observed estimate onto the underlying liability scale the heritability estimate was h2 = 0.43.

Animals↗

PubMed1975

[Computer simulation of cell renewal systems].

This paper deals with a block diagram which describes the structure of the control of erythropoiesis by negative feedback loops. The model is transformed into an adequate simulation program using a special block-oriented programming language called ASIM (Analoge SIMulation). For both normal and diseased states of the blood forming process the dynamic responses of the erythrocytes and reticulocytes are simulated by a digital computer analysis. The computer simulation includes different forms of anemia caused by parameter variations as well as by structural alterations. Rising oscillations are obtained too in multiloop control systems containing complex paths with minor loops, which for example take into account the erythrocytic chalones. The described model shows that rising oscillations, that are unstable control loops, can be produced by changing the control-loop structure as well as by parameter changes. In case of malignant disorders such failures becoming effective in oscillations are discussed as parts of disturbed homoeostasis. The results of these studies obtained by simulation should especially stimulate scientists working in the fields of biology and medicine to new test series to verify the proposed hypothesis.

Anemia↗

PubMed2003

Statistical validation based on parametric receiver operating characteristic analysis of continuous classification data.

RATIONALE AND OBJECTIVES: The accuracy of diagnostic test and imaging segmentation is important in clinical practice because it has a direct impact on therapeutic planning. Statistical validations of classification accuracy was conducted based on parametric receiver operating characteristic analysis, illustrated on three radiologic examples, MATERIALS AND METHODS: Two parametric models were developed for diagnostic or imaging data. Example 1: A semi-automated fractional segmentation algorithm was applied to magnetic resonance imaging of nine cases of brain tumors. The tumor and background pixel data were assumed to have bi-beta distributions. Fractional segmentation was validated against an estimated composite pixel-wise gold standard based on multi-reader manual segmentations. Example 2: The predictive value of 100 cases of spiral computed tomography of ureteral stone sizes, distributed as bi-normal after a non-linear transformation, under two treatment options received. Example 3: One hundred eighty cases had prostate-specific antigen levels measured in a prospective clinical trial. Radical prostatectomy was performed in all to provide a binary gold standard of local and advanced cancer stages. Prostate-specific antigen level was transformed and modeled by bi-normal distributions. In all examples, areas under the receiver operating characteristic curves were computed. RESULTS. The areas under the receiver operating characteristic curves were: Example 1: Fractional segmentation of magnetic resonance imaging of brain tumors: meningiomas (0.924-0.984); astrocytomas (0.786-0.986); and other low-grade gliomas (0.896-0.983). Example 3: Ureteral stone size for treatment planning (0.813). Example 2: Prostate-specific antigen for staging prostate cancer (0.768). CONCLUSION: All clinical examples yielded fair to excellent accuracy. The validation metric area under the receiver operating characteristic curves may be generalized to evaluating the performances of several continuous classifiers related to imaging.

Algorithms↗

PubMed2004

Food chain chaos with canard explosion.

The "tea-cup" attractor of a classical prey-predator-superpredator food chain model is studied analytically. Under the assumption that each species has its own time scale, ranging from fast for the prey to intermediate for the predator and to slow for the superpredator, the model is transformed into a singular perturbed system. It is demonstrated that the singular limit of the attractor contains a canard singularity. Singular return maps are constructed for which some subdynamics are shown to be equivalent to chaotic shift maps. Parameter regions in which the described chaotic dynamics exist are explicitly given.

Adaptation, Physiological↗