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PubMed2005

[The interaction of vitamin B6 with the human serum albumin].

The Human Serum Albumin (HSA) can emit fluorescence (lamda(em) = 350 nm) under irradiation of ultraviolet light (lamda(ex) = 296 nm). After the vitamin B6 (B6) was added into HSA solution the fluorescence of HSA was quenched partially. This quenching was static quenching owing to the fact that ro (fluorescence life time (life time of the molecule excitation state) of HSA without B6) equaled to tau(i) (fluorescence life time of HSA with B6). The formation constant K between HSA and B6 was observed from the experiment, and then the binding distance R0 was determined (R0 = 1.872 nm). The CD spectra of samples (HSA, [HSA] = 1 x 10(-5) mol x L(-1), HSA +B6, [B6] = 5 x 10(-8), 1.5 x 10(-7), 2.5 x 10(-7), 3.5x 10(-7), 4.5x 10(-7) mol x L(-1)) were measured, and all CD spectra were almost the same. From [theta] values, the contents (percent content) of four structure(alpha-Helix, beta-Pleated, Beta-corner, and Randon wind) of samples can be calculated, and we find that all samples contain almost the same structure contents.

Algorithms↗

PubMed2006

MotifCut: regulatory motifs finding with maximum density subgraphs.

MOTIVATION: DNA motif finding is one of the core problems in computational biology, for which several probabilistic and discrete approaches have been developed. Most existing methods formulate motif finding as an intractable optimization problem and rely either on expectation maximization (EM) or on local heuristic searches. Another challenge is the choice of motif model: simpler models such as the position-specific scoring matrix (PSSM) impose biologically unrealistic assumptions such as independence of the motif positions, while more involved models are harder to parametrize and learn. RESULTS: We present MotifCut, a graph-theoretic approach to motif finding leading to a convex optimization problem with a polynomial time solution. We build a graph where the vertices represent all k-mers in the input sequences, and edges represent pairwise k-mer similarity. In this graph, we search for a motif as the maximum density subgraph, which is a set of k-mers that exhibit a large number of pairwise similarities. Our formulation does not make strong assumptions regarding the structure of the motif and in practice both motifs that fit well the PSSM model, and those that exhibit strong dependencies between position pairs are found as dense subgraphs. We benchmark MotifCut on both synthetic and real yeast motifs, and find that it compares favorably to existing popular methods. The ability of MotifCut to detect motifs appears to scale well with increasing input size. Moreover, the motifs we discover are different from those discovered by the other methods. AVAILABILITY: MotifCut server and other materials can be found at motifcut.stanford.edu.

Algorithms↗

PubMed1995

Ventricular fibrillation, automatic external defibrillators, and the United States Food and Drug Administration: confrontation without comprehension.

More people die in the United States each day of potentially reversible VF than of any other cause of death, reversible or not. Early defibrillation is the definitive treatment. Automated external defibrillation is a proven technology now confirmed to have saved thousands of lives. As with all medical devices and technology, perfection is not possible. Some problems, such as those represented by the two cases discussed in this article, are inevitable and acceptable and give little cause for alarm. One would not stop penicillin from being manufactured and distributed because of a sudden, unexpected allergic reaction in one patient (error of commission) or an unexpected resistant organism in another (error of omission). The FDA must understand that AEDs, even if they are imperfect, are not anywhere near as dangerous as no defibrillator at all. AEDs have finally allowed many EMS systems to achieve early defibrillation. Discontinuing use of AEDs or closing AED manufacturers could mean a significant number of lives lost unnecessarily. Therefore EMS agencies planning to implement early-defibrillation programs should continue with such plans. Why the agents of an important federal regulatory agency have singled out this technology for an intense review puzzles many observers in the medical-device field. Two meetings have been hosted by officials of the FDA to discuss the continuing concern the FDA officials have expressed over automated defibrillation technology. These meetings included representatives from the AHA, the American College of Cardiology, ACEP, defibrillator manufacturers, and other interested organizations. The FDA leadership has repeatedly focused on data acquired through the FDA Medical Device Reporting systems. Congress requires the FDA to investigate reports of problems with "critical medical devices." Because the indication for the use of a defibrillator is cardiac arrest, there will inevitably be a high association between defibrillator use and patient deaths. FDA personnel may view such reports of device problems in association with patient deaths as evidence that an intrinsically flawed technology has reached the marketplace without rigorous testing and evaluation. From the clinician's perspective, however, these reports represent a small numerator over a huge denominator of daily, lifesaving clinical use. The non-FDA participants at the two meetings have stated that the FDA complaints appear to be random and reveal a lack of understanding of AED technology.(ABSTRACT TRUNCATED AT 400 WORDS)

Algorithms↗

PubMed2003

Multi-wavelength fluorescence-quenching model for determination of Cu2+ conditional stability constants and ligand concentrations of fulvic acid.

In this work, a multi-wavelength model (MWM) is developed. It uses fluorescence bands in the fulvic acid (FA) spectrum that quench upon binding of inorganic Cu2+ to FA. Quenching data at pH values of 5, 6, and 7 are placed in sets, containing fluorescence measures at select wavelengths versus added copper (CM). Intensity data of wavelength set 1 are obtained from 25 nm constant offset synchronous fluorescence spectra (SyF), in which are observed distinct peaks (lambda(ex) = 415 nm, lambda(em) = 440 nm; and lambda(ex) = 471 nm, lambda(em) = 496 nm). Wavelength set 2 intensity data are obtained from the FA fluorescence excitation and emission maxima (lambda(ex) = 335 nm, lambda(em) = 450 nm; and X(ex) = 471 nm, lambda(em) = 496 nm). Application of MWM shows that the multi-wavelength data sets characterize ligands of different binding strength (log K(x)) and concentration (C(Lx)). Corresponding to pH values of 5, 6, and 7, mean and standard deviation values for wavelength set 1 are log K(415/440) = 4.66 (0.12), 5.03 (0.12), and 5.05 (0.08), log K(471/496) = 4.93 (0.06), 5.27 (0.11), and 5.39 (0.09), C(415/440) = 3.1 (1.5), 10.9 (4.5), and 7.9 (3.9) microM, C(471/496) = 14.3 (3.0), 1.7 (0.6), and 1.4 (0.5) microM. And for wavelength set 2, log K(335/450) = 4.50 (0.03), 4.96 (0.27), and 5.22 (0.08), log K(471/496) = 5.02 (0.04), 5.42 (0.32), and 5.71 (0.09), C(335/450) = 8.8 (0.5), 21.9 (7.9), and 18.7 (0.3) microM, C(471/496) = 21.0 (2.5), 7.17 (1.2), and 7.09 (0.3) micrpM. The ability of the 415/440 nm SyF transect to characterize the main excitation and emission maximum of FA at 335/440 nm is evaluated. Relatively low concentration values returned by the model for this transect (415/440 nm) suggest that it is not entirely illustrative of the maximum. The model predictive capability is verified at pH 6 with two fluorescing Cu2+ chelating organic compounds, L-tyrosine and salicylic acid. This test confirms that the model is capable of providing good estimates of equilibrium binding parameters from multi-wavelength measurements of a mixed ligand system.

Algorithms↗

PubMed2004

Outcome of out-of-hospital cardiac arrest--why do physicians withhold resuscitation attempts?

OBJECTIVE: To describe the outcome of out-of-hospital cardiac arrest (OHCA) with a focus on why physicians withhold resuscitation attempts. METHODS: Prospective collection of data during 12 months by the anaesthesiologists from the Advanced Life Support unit (ALS) of the Emergency Medical Service (EMS) according to the Utstein template. RESULTS: In total, 499 OHCA were analysed and 266 patients received cardiopulmonary resuscitation (CPR) by the ALS unit. Initial rhythm was ventricular fibrillation (VF)/pulseless ventricular tachycardia (VT) in 35%, asystole in 38%, and other rhythm in 27%. Of the 266 treated patients, 83 (31%) patients had a spontaneous circulation on admission to hospital. Survival to discharge from hospital was 6.2% for all cases of OHCA, 11.7% for all 266 treated patients, and 20.5% for patients with witnessed cardiac arrest and presumed cardiac aetiology in VF. On arrival, the physician decided in 233 cases to withhold or discontinue CPR. The explanation for this was prolonged anoxia (74%), terminal cancer (8%), and severe trauma (7%). The most common incident locations were the patient's home and nursing homes. These locations were more common in the group where resuscitation was not attempted and these patients were older and the proportions of females and asystole were significantly higher. Bystander CPR was provided in 82 (16%) overall, but only in 8 (3%) in the group where resuscitation was not attempted. CONCLUSION: Survival to discharge from hospital in all cases of OHCA was 6.2% but 20.5% in witnessed, presumed cardiac aetiology in VF. The decision to withhold resuscitation was based upon presumed prolonged anoxia in the majority of cases.

Adolescent↗

PubMed2002

Developmental traits affecting low-temperature tolerance response in near-isogenic lines for the Vernalization locus Vrn-A1 in wheat (Triticum aestivum L. em Thell).

Investigation of low-temperature (LT) tolerance in cereals has commonly led to the region of the vyn-A1 vernalization gene or its homologue in related genomes. Two cultivars, one a non-hardy spring wheat and one a very cold-hardy winter wheat, whose growth habits are determined by the Vrn-A1 (spring habit) and vrn-A1 (winter habit) alleles, were chosen to produce reciprocal near-isogenic lines (NILs). These lines were then used to determine the relationship between rate of phenological development and the degree and duration of LT tolerance gene expression. Each allele was isolated in the genetic backgrounds of the non-hardy spring wheat 'Manitou' and the very cold-hardy winter wheat 'Norstar'. The effects of each allele on phenological development and low-temperature tolerance (LT50) were determined at regular intervals over a 4 degrees C acclimation period of 0-98 d. The vegetative/reproductive transition, as determined by final leaf number (FLN), was found to be a major developmental factor influencing LT tolerance. Possession of a vernalization requirement increased both the length of the vegetative growth phase and LT tolerance. Similarly, increased FLN in spring Norstar and winter Manitou NILs delayed their vegetative/reproductive transition and increased their LT tolerance relative to Manitou. Although the winter Manitou NILs had a lower FLN than the spring Norstar NILs, they were able to extend their vegetative stage to a similar length by increasing the phyllochron (interval between the appearance of successive leaves). Cereal plants have four ways of increasing the length of the vegetative phase, all of which extend the time that low-temperature tolerance genes are more highly expressed: (1) vernalization; (2) photoperiod responses; (3) increased leaf number; and (4) increased length of the phyllochron.

Acclimatization↗

PubMed2001

Accurate length determination of DNA molecules visualized by atomic force microscopy: evidence for a partial B- to A-form transition on mica.

Achieving the most correct estimate of the contour length of digitized DNA molecules is a key aspect of the microscopic analysis of nucleic acids by either electron microscopy (EM) or atomic force microscopy (AFM). Six different methods, that are mathematically not too complex and suited for common, practical use, have been tested here using simulated polymers in two dimensions and real DNA molecules (564, 1054, 2049 and 4297 bp long) imaged in air by AFM. The main result is that the frequently used Freeman estimator (L(F) = n(e) + square root 2n(o)) overestimates the real contour length of the polymers by about 4%. More accurate estimates are obtained with the Kulpa estimator (L(K) = 0.948n(e) + 1.343n(o)) or with the corner count estimator (L(C) = 0.980)n(e) + 1.406n(o) - 0.091n(c)). In the range of the DNA sizes and magnifications we have considered, however, the best results are obtained with an ad hoc developed routine that smoothes the DNA trace by a polynomial fitting of degree 3 over a moving window of 5 points. Under these conditions, the difference between the measured and the real contour length of the molecules is less than 0.4%. The accuracy of this procedure allowed us to reveal a discrete, size-dependent, shortening of DNA molecules deposited onto mica under low salt conditions and imaged in air by AFM. Awareness of this structural alteration, that can be attributed to a partial transition from B- to A-form DNA, may lead to a more correct interpretation of DNA molecules or protein-DNA complexes imaged by AFM.

Algorithms↗

PubMed2003

Characteristics of crashes that increase the risk of serious injuries.

The advent of Automatic Crash Notification Systems (ACN) offers the possibility of immediately locating crashes and of determining the crash characteristics by analyzing the data transmitted from the vehicle. A challenge to EMS decision makers is to identify those crashes with serious injuries and deploy the appropriate rescue and treatment capabilities. The objective of this paper is to determine the crash characteristics that increase the risk of serious injury. Within this paper, regression models are presented which relate occupant, vehicle and impact characteristics to the probability of serious injury using the Maximum Abbreviated Injury Scale Level (MAIS). The accuracy of proposed models were evaluated using National Automotive Sampling System/ Crashworthiness Data System (NASS/CDS) and Crash Injury Research and Engineering Network (CIREN) case data. Cumulatively, the positive prediction rate of models identifying the likelihood of MAIS3 and higher injuries was 74.2%. Crash mode has a significant influence of injury risk. For crashes with 30 mph deltaV, the risk of MAIS3+ injury for each mode is 38.9%, 83.8%, 47.8% and 19.9% for frontal, near side, far side and rear impact crashes, respectively. In addition to deltaV, a number of crash variables were identified that assist in the accurate prediction of the probability of MAIS 3+ injury. These variables include occupant age, partial ejection, safety belt usage, intrusion near the occupant, and crashes with a narrow object. For frontal crashes, added crash variables include air bag deployment, steering wheel deformation, and multiple impact crashes. The quantitative relationship between each of these crash variables and injury risk has been determined and validated by regression analysis based on NASS/CDS and CIREN data.

Abbreviated Injury Scale↗

PubMedDate not supplied

Flight crew airway management in four settings: a six-year review.

OBJECTIVE: To analyze flight crew airway management in four different settings (in flight, at trauma scenes, in ambulance, and in referring hospitals) and in two different aircraft used by the same helicopter EMS (HEMS) service. The null hypothesis was that there was no association between practice setting, or aircraft, and airway practices or success rate. METHODS: This retrospective study analyzed all patients in whom advanced airway management was attempted by the HEMS service during the study period October 1991 through October 1997. Data used were from flight records of Boston MedFlight Critical Care Transport Service, which uses a nurse/paramedic crew and had a paralytic-assisted intubation protocol in place. Data were analyzed with chi-square and Fisher's exact testing, risk ratio analysis, and logistic regression. RESULTS: Advanced airway management was attempted in 722 patients, with an airway placed in 705 (97.8%). Intubation success was unrelated to site of airway management (p = 0.14), but patients were more likely to have intubation attempted prior to flight (as opposed to in flight) if the crew were in the AS365N2 Dauphin as compared with the BK-117 (p<0.0001). In addition, patients were 0.77 times as likely (95% confidence interval, 0.68-0.88) to receive paralytic-facilitated intubation if airway management occurred in the hospital setting as compared with other sites. CONCLUSIONS: While HEMS crew airway management success rates are equally high in all practice settings, airway management decision making and practice appear to be significantly influenced by practice setting and aircraft type. These data support contentions that nonphysician HEMS crews can effectively manage airways in a variety of circumstances.

Adult↗

PubMed2003

Topology representing network enables highly accurate classification of protein images taken by cryo electron-microscope without masking.

In single-particle analysis, a three-dimensional (3-D) structure of a protein is constructed using electron microscopy (EM). As these images are very noisy in general, the primary process of this 3-D reconstruction is the classification of images according to their Euler angles, the images in each classified group then being averaged to reduce the noise level. In our newly developed strategy of classification, we introduce a topology representing network (TRN) method. It is a modified method of a growing neural gas network (GNG). In this system, a network structure is automatically determined in response to the images input through a growing process. After learning without a masking procedure, the GNG creates clear averages of the inputs as unit coordinates in multi-dimensional space, which are then utilized for classification. In the process, connections are automatically created between highly related units and their positions are shifted where the inputs are distributed in multi-dimensional space. Consequently, several separated groups of connected units are formed. Although the interrelationship of units in this space are not easily understood, we succeeded in solving this problem by converting the unit positions into two-dimensional (2-D) space, and by further optimizing the unit positions with the simulated annealing (SA) method. In the optimized 2-D map, visualization of the connections of units provided rich information about clustering. As demonstrated here, this method is clearly superior to both the multi-variate statistical analysis (MSA) and the self-organizing map (SOM) as a classification method and provides a first reliable classification method which can be used without masking for very noisy images.

Algorithms↗

PubMed2004

Comparison of the accuracy of methods of computational haplotype inference using a large empirical dataset.

BACKGROUND: Analyses of genetic data at the level of haplotypes provide increased accuracy and power to infer genotype-phenotype correlations and evolutionary history of a locus. However, empirical determination of haplotypes is expensive and laborious. Therefore, several methods of inferring haplotypes from unphased genotypic data have been proposed, but it is unclear how accurate each of the methods is or which methods are superior. The accuracy of some of the leading methods of computational haplotype inference (PL-EM, Phase, SNPHAP, Haplotyper) are compared using a large set of 308 empirically determined haplotypes based on 15 SNPs, among which 36 haplotypes were observed to occur. This study presents several advantages over many previous comparisons of haplotype inference methods: a large number of subjects are included, the number of known haplotypes is much smaller than the number of chromosomes surveyed, a range in values of linkage disequilibrium, presence of rare SNP alleles, and considerable dispersion in the frequencies of haplotypes. RESULTS: In contrast to some previous comparisons of haplotype inference methods, there was very little difference in the accuracy of the various methods in terms of either assignment of haplotypes to individuals or estimation of haplotype frequencies. Although none of the methods inferred all of the known haplotypes, the assignment of haplotypes to subjects was about 90% correct for individuals heterozygous for up to three SNPs and was about 80% correct for up to five heterozygous sites. All of the methods identified every haplotype with a frequency above 1%, and none assigned a frequency above 1% to an incorrect haplotype. CONCLUSIONS: All of the methods of haplotype inference have high accuracy and one can have confidence in inferences made by any one of the methods. The ability to identify even rare (>/= 1%) haplotypes is reassuring for efforts to identify haplotypes that contribute to disease in a significant proportion of a population. Assignment of haplotypes is relatively accurate among subjects heterozygous for up to 5 sites, and this might be the largest number of SNPs for which one should define haplotype blocks or have confidence in haplotype assignments.

Algorithms↗

PubMed1997

Unwitnessed out-of-hospital cardiac arrest: is resuscitation worthwhile?

STUDY OBJECTIVE: To determine the epidemiology of unwitnessed out-of-hospital cardiac arrest and the factors associated with survival after resuscitation using the Utstein style data collection. METHODS: We conducted a prospective cohort study in a 525,000-population city served by a single EMS system comprising a tiered response with physicians in the field. We studied consecutive unwitnessed out-of-hospital cardiac arrests that occurred between January 1, 1994, and December 31, 1995. We determined survival from cardiac arrest to discharge from hospital and the factors associated with survival. RESULTS: Of the 809 patients for whom resuscitation was considered, 205 (25.3%) had sustained unwitnessed arrests. Cardiac origin of arrest was verified in 52% of cases. The most common noncardiac causes of arrest were trauma, intoxication, near-drowning, and hanging. In 150 patients (73.2%) the presenting rhythm was asystole, in 28 (13.6%) it was pulseless electrical activity, and in 27 (13.2%) it was ventricular fibrillation. Resuscitation was attempted in 162 cases, 59 (36.4%) of whom demonstrated return of spontaneous circulation; 45 (27.8%) were hospitalized alive, and 8 (4.9%) were discharged. The survivors represented 6.7% of all out-of-hospital cardiac arrest survivors during the study period. Survival was most likely if patients presented with pulseless electrical activity; none of the patients with asystole of cardiac origin survived. Sex (P = .032), age (inverse relationship, P = .0004), scene of collapse (P = .042), and interval from call receipt to arrival of first responders (P = .004) were associated with survival. In a logistic-regression model, near-drowning remained an independent factor of survival (odds ratio, 15.5; 95% confidence interval, 1.2 to 200). A routine priority dispatching protocol differentiated cardiac arrest patients with survival potential from those who already had irreversible signs of death. CONCLUSION: This survey shows that survival after unwitnessed out-of-hospital cardiac arrest is unlikely with an initial response of basic life support alone. Withdrawal of resuscitation should be considered if an adult victim of unwitnessed cardiac arrest is found in asystole and the arrest is of obvious cardiac origin.

Adolescent↗

PubMed1995

High-dose epinephrine in pediatric out-of-hospital cardiopulmonary arrest.

OBJECTIVE: To compare the efficacy of high-dose epinephrine (HDE) and standard-dose epinephrine (SDE) for out-of-hospital treatment of pediatric cardiopulmonary arrest (CPA). DESIGN: Forty-eight-month retrospective cohort study. SETTING: Prehospital emergency medical services (EMS) system of a large metropolitan region. PATIENTS: All children younger than 18 years of age, who suffered nontraumatic CPA, did not meet local EMS criteria for death in the field, and were treated by paramedics according to EMS pediatric CPA protocols. INTERVENTIONS: Paramedics administered HDE (> 0.1 mg/kg), SDE (< 0.1 mg/kg), or no epinephrine (NE), based on base hospital physician order and availability of access for drug delivery. Protocols permitted either HDE or SDE. The drug was given through an endotracheal tube, intraosseous line, or intravenous line. MAIN OUTCOME MEASURES: Return of spontaneous circulation (ROSC) and return of an organized electrical rhythm (ROER) in the ambulance and emergency department, hospital admission, hospital discharge, and short- and long-term neurologic outcome by pediatric cerebral performance category (PCPC) score. RESULTS: During the study period, 65 children met inclusion criteria and underwent attempted out-of-hospital resuscitation. Forty patients (62%) received HDE (mean dose +/- SD, 0.19 +/- 0.06 mg/kg); 13 patients (20%) received SDE (mean dose +/- SD, 0.02 +/- 0.02 mg/kg); and 12 patients (18%) received NE. The HDE and SDE groups were statistically different only in epinephrine dose but not in age, gender, proportion of asystolic presenting rhythms, success of endotracheal tube intubation or intraosseous line insertion, rate of ROSC, rate of ROER, survival, or proportion of sudden infant death syndrome final diagnoses. Fifty-four children (83%) presented in asystole, 5 (8%) had pulseless electrical activity (PEA), and 6 (9%) had ventricular fibrillation (VF). None presented with either supraventricular tachycardia or ventricular tachycardia. Thirty-nine patients receiving HDE had asystole or VF as presenting rhythms, 4 (10%) had ROER, and 1 had ROSC. The single child receiving HDE presenting with PEA did not have ROSC. Ten patients receiving SDE had asystole or VF, 2 (20%) had ROER, and none had ROSC. There were 3 children receiving SDE who had PEA, and 1 had ROSC. Eleven patients receiving NE had asystole or VF, and none had ROER. One child receiving NE had PEA and ROSC. Altogether, 1 patient receiving HDE, 1 receiving SDE, and 1 receiving NE had ROSC in the field, which continued in the emergency department; all 3 were admitted to the hospital. Two children (3%), 1 receiving HDE and 1 receiving SDE, survived to hospital discharge. The survivor receiving HDE had spastic quadriplegia and profound neurologic handicaps at discharge, with a PCPC score of 4 (severe disability with daily living milestones below the 10th percentile and excessive dependence on others for provision of activities of daily living); at a 1-year follow-up, she had a PCPC score of 4. The survivor receiving SDE was neurologically healthy at discharge; at discharge and at follow-up at age 1 year, she had a PCPC score of 1 (age-appropriate level of functioning and developmentally appropriate). CONCLUSIONS: HDE does not seem to improve the rates of ROER and ROSC, hospital admission, survival, or neurologic outcome when compared with SDE for treatment of out-of-hospital pediatric CPA. A large, blinded prospective clinical trial testing different epinephrine doses is necessary to determine drug efficacy and safety. Future pediatric CPA studies must standardize reporting of core data elements, using the adult Utstein criteria modified for pediatrics, to allow valid treatment comparisons. Overall, survival in out-of-hospital pediatric CPA is dismal.(ABSTRACT TRUNCATED)

Adolescent↗