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Biomedical subjects

M T Morgan

Publications and source records attributed to M T Morgan.

At least 19 recordsLinked to original sources

Genome-wide deleterious mutation favors dispersal and species integrity.

Here I develop the idea that ubiquitous harmful genome-wide mutation with local differentiation favors dispersal, even though migration reduces average fitness. Historical contingency of the mutational process means that demes (sub-populations) differentiate from one another. Deleterious or lethal partially recessive mutations carried by migrants then do not encounter similar mutations in the recipient deme. Migrant offspring have higher fitness than offspring of residents, because migrant offspring are heterozygous rather than homozygous for harmful mutations. The advantage is inversely related to local inbreeding depression. Genome-wide deleterious mutation favors the evolution of dispersal, which in turn enhances the genetic integrity of the species.

Animals↗

Consequences of life history for inbreeding depression and mating system evolution in plants.

Many plants are perennial, but most studies of inbreeding depression and mating system evolution focus on annuals. This paper extends a population genetic model of inbreeding depression due to recessive deleterious mutations to perennials. The model incorporates life history and mating system variation, and multiplicative selection across many genetic loci. In the absence of substantial mitotic mutation, perennials have higher mean fitness and lower, or even negative, inbreeding depression than annuals with the same mating system. As in annuals, self fertilization exposes deleterious recessive mutations to selection, increasing mean fitness and decreasing inbreeding depression. Including mitotic mutation decreases mean fitness while increasing inbreeding depression. Perenniality introduces a kind of selective sieve, such that strongly recessive mutations contribute disproportionately to mean fitness and inbreeding depression. In the presence of high mitotic mutation, this selective sieve may provide a mechanistic basis for high inbreeding depression observed in some long lived perennials. Without substantial mitotic mutation, it is difficult to reconcile genetically based models of inbreeding depression with the empirical generalization that perennials outcross while related annuals self fertilize.

Biological Evolution↗

Transposable element number in mixed mating populations.

Theoretical population genetic studies of transposable elements focus almost exclusively on random mating species, whereas many plants reproduce through partial or substantial self-fertilization. Here I develop computer simulation and analytic approximations of simplified element dynamics (transposition balanced by selective elimination) in partially self-fertilizing populations, using Ty1-copia elements for biological inspiration. Under the most plausible models and parameter values, element numbers decrease with self-fertilization when element insertions are deleterious, but may increase when ectopic exchange regulates element number. Conclusions for models of ectopic exchange depend in part on parameters for which little firm empirical evidence is available. Small changes in selfing rate can lead to abrupt changes in element number when homozygous and heterozygous elements have markedly different fitness effects. Equilibrium element numbers can be sensitive to population size, especially at high selfing rates. Elements are frequently lost in small highly selfing populations under the deleterious insertion model. In contrast, small highly selfing populations can accumulate very large numbers of elements under ectopic exchange. Empirical data on element number and localization in plants with different mating systems suggests that deleterious insertion, rather than ectopic exchange, may regulate element number. Limitations to available empirical data, especially the lack of comparison between closely related species differing in mating system, mean that this conclusion is tentative.

Breeding↗

Using genetic markers to directly estimate male selection gradients.

We present an analysis of Raphanus raphanistrum and simulations illustrating the utility of directly estimating male phenotypic selection gradients using genetic markers. The method offers a much more refined characterization of selection than attempting to assign paternity to individual progeny. Our analysis of R. raphanistrum reveals selection on remarkably fine features of floral morphology, including anther exsertion, that were opaque to previous approaches. The new results also undermine a previous conclusion that selection on wild radish floral morphology acts primarily through female fitness. Simulation results show that selection gradients on the order of beta = 0.1-0.2 can be readily detected with allozyme markers in moderate-sized (< 200 paternal individuals) populations. Highly polymorphic (e.g., microsatellite) markers will likely detect fine scale selection (beta < 0.1) in larger populations (> or = 400 individuals). Increased progeny sample size, by sampling either additional maternal families or more progeny per maternal parent, partly compensates for low exclusion probability. Increasing the number of possible fathers without changing progeny sample size decreases the ability to detect selection, especially at lower exclusion probabilities. Sampling only some male genotypes reduces the power to detect selection and biases (underestimates) the magnitude of the selection gradient estimate.

Brassicaceae↗

Assessment of fresh pork color with color machine vision.

Currently, fresh pork color is visually evaluated using either the Japanese Pork Color Standards (JPCS) or the National Pork Producers Council Pork Quality Standards (NPPC) as a reference. Although useful, visual evaluation of meat color can vary with evaluator and may be quite expensive. In this study, three separate studies were used to compare the ability of color machine vision (CMV) and untrained panelists to evaluate pork color. Panels visually evaluated over 200 pork loin chops using either the JPCS or NPPC reference standards. Results from each panel were used to evaluate the ability of the CMV to sort pork loin chops based on the same criteria. Representative samples, typical of each color class, were used to train neural-network-based image processing software. After training, the CMV system was used to evaluate quality classes of pork samples based on color distribution. Classification by CMV was compared with the average panel score, rounded to the nearest integer. Training the CMV system using images of actual meat samples resulted in a stronger correlation to panel scores than training with either set of artificial color standards. Agreement between the CMV system and the panels was as high as 90%. Agreement between individual panelists and the integer panel average (52 to 85%) was less than that observed for CMV classification. Finally, the on-line performance of CMV using a laboratory conveyor system was simulated by repeatedly classifying 37 samples at a speed of 1 sample per second. Collectively, these results demonstrate that CMV is a rapid and repeatable means of evaluating pork color.

Animals↗

Results of a 4-hour endotracheal intubation class for EMT-basics.

STUDY OBJECTIVE: In 1994, the Department of Transportation made endotracheal intubation an optional EMT-Basic skill. To data, there have been no studies addressing the ability of this group to learn or perform this skill. We used a standarized mannequin test to perform a prospective evaluation of this intubation skills of basic EMTs immediately after a 4-hour course on endotracheal intubation. We hypothesized that the intubation success rates would be comparable with those of other types of providers newly trained in this skill. METHODS: Eighty-three EMTS were selected/recruited from four EMS provider agencies. Ninety-six percent of the EMTs were men, and the average age was 38 years; average length of EMT experience was 9.4 years. Training was provided in classes of 6 to 14 persons and included 1 hour of didactic instruction, a 1-hour demonstration of intubation techniques, and 90 minutes of supervised practice with the mannequins in groups of 2 to 4 persons. Testing followed American Heart Association guidelines. Interrater reliability of test criteria was assessed. RESULTS: Ninety-four percent (95% confidence interval 86% to 98%) of the EMTs passed the examination by intubating the mannequin within 35 seconds within 3 attempts. Of the successful EMTs, 94% succeeded on their first attempt, 3% on their second attempt, and 3% on their third. There were three esophageal intubations; all were detected immediately. Interrater agreement was 100% on the pass/fail decision. CONCLUSION: This 4-hour class trained basic EMTs to perform endotracheal intubation on mannequins with a success rate of 94%. Further research should confirm the ability of EMT-Basics to detect esophageal intubation and address the retention of intubation skills, the applicability of these skills to the field, and the components of this course that were responsible for its success.

Adult↗

Properties of maximum likelihood male fertility estimation in plant populations.

Computer simulations are used to evaluate maximum likelihood methods for inferring male fertility in plant populations. The maximum likelihood method can provide substantial power to characterize male fertilities at the population level. Results emphasize, however, the importance of adequate experimental design and evaluation of fertility estimates, as well as limitations to inference (e.g., about the variance in male fertility or the correlation between fertility and phenotypic trait value) that can be reasonably drawn.

Computer Simulation↗

Effect of cardiologist ECG review on emergency department practice.

STUDY OBJECTIVE: To determine the effect of cardiology review of ECGs on emergency department practice. METHODS: We carried out a prospective cohort study at an urban teaching ED. Our subjects were adult patients undergoing electrocardiography. We prospectively collected 1,000 consecutive ECGs and classified them by severity according to the following system: class 1, normal or minor abnormalities only; class 2, abnormalities with potential to alter case management; and class 3, potentially life-threatening abnormalities. Actual ECG readings by ED physicians (who had access to computerized interpretations at the time of treatment) were compared with those of staff cardiology quality-assurance reviewers; if they were not in agreement, an expert cardiology panel blindly chose the superior interpretation. Subsequently, an expert emergency physician panel reviewed discordant readings for discharged patients to determine the need for further action. RESULTS: Of 1,000 ECGs, the readings for 190 (19%) were significantly discordant. The expert cardiology panel preferred the ED reading in 72 cases (38%) and the staff cardiology reading in 118 (62%). In 30 other cases no ED reading was recorded in the medical record. Of the 148 cases in which the expert cardiology panel agreed with the cardiology reading or there was no ED reading, 102 patients were admitted and 46 discharged. Of the 46 discharges, 8 cardiology readings were categorized as class 1, leaving only 38 cases in which the staff cardiology reading might have affected the ED decision to discharge a patient. All of these readings were in class 2, with the exception of one unclassifiable diagnosis. There were no class 3 readings. On expert emergency physician panel review of these 38 ECGs and interpretations, only 8 (.8%, 95% confidence interval, .3% to 1.6%) were considered sufficiently important to warrant chart review. In actual practice, none of these cases was affected by the ECG quality-assurance (QA) process. Two of these patients died during our 1-year follow-up. In one of these cases, the ECG QA process could have altered the patient's outcome. CONCLUSION: The existing ECG review process as mandated by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) will likely have minimal influence on patient outcomes at our institution. We should establish the effectiveness of this mandated QA process before committing scarce resources to its performance.

Adult↗

Failure to agree on the electrocardiographic diagnosis of ventricular tachycardia.

STUDY OBJECTIVE: To determine the extent of interobserver agreement in the ECG diagnosis of ventricular tachycardia (VT) by using a four-step algorithm and three observers. METHODS: Simulated emergency department setting from records of an urban university teaching hospital. All ECGs taken in the ED during a 2-year period that showed a QRS duration of more than 120 msec and a heart rate faster than 110 beats per minute were reviewed. ECGs were categorized as demonstrating sinus rhythm (SR), irregular broad-complex tachycardia (I-BCT), or regular broad-complex tachycardia (BCT). Copies of the BCT ECGs and short clinical histories were given to each of three emergency physicians, who used a published, four-step algorithm (the Brugada algorithm) to categorize the BCT ECGs as indicating VT, indicating supraventricular tachycardia with aberrancy (SVT-A), or indeterminate. Interobserver agreement was assessed with the K-statistic. RESULTS: The records contained 178 ECGs, 88 of which were SR, 63 I-BCT, and 27 BCT. The 27 BCT ECGs were selected for review. The emergency physicians disagreed with each other 22% of the time in differentiating VT from SVT-A (K = .58). CONCLUSION: Application of the algorithm to actual clinical practice in the ED would probably result in the misdiagnosis of a substantial minority of patients having BCT, with potentially serious adverse consequences.

Adult↗

Electrical measurement for detecting early postmortem changes in porcine muscle.

Use of electrical measurements to detect quality defects in porcine muscle in the early postmortem period was evaluated. Justification for use of a tetrapolar, constant current electrode configuration instead of bipolar electrodes was provided for measurements at low frequencies. Interrelationships among electrical properties, pH values, ATP decline, temperature, time postmortem, and final water-holding capacity (WHC) of porcine muscle were quantified using 25 hogs. Immediately after exsanguination, a section of the left longissimus muscle (LM) was excised to obtain rigor shortening patterns and complex impedance measurements over a 10-h period at 37 degrees C. Complex impedance measurements were taken using a tetrapolar electrode configuration at 1 kHz and .156 mA. At 15, 45, and 90 min postmortem, pH, ATP/IMP absorbance (R), and conductivity measured by the Tecpro Pork Quality Meter (PQM) were measured on the right side LM. At 24 h postmortem, WHC, pH, R, PQM, Hunter Color Lab values, and subjective quality scores were evaluated on the left LM. The WHC measurements were used to group carcasses into normal (n = 17) and abnormal (n = 8) categories. Mean pH and R at 45 and 90 min were different (P < .05) but pH at 24 h was not different between the normal and abnormal groups. Onset and completion of rigor were more rapid in carcasses with low WHC (P < .05). The PQM values were greater (P < .05) in the abnormal group at 90 min and 24 h postmortem. Excised muscle measurements of relative impedance (Z*) and phase (theta*) showed Z* and theta* increased more rapidly within the first 15 min postmortem (P < .1) for samples with abnormal WHC. However, one PSE carcass showed an immediate rapid decrease in Z* and theta*. Results suggest measurement of rate of change of impedance and phase angle before 90 min postmortem would be a better prediction of ultimate quality than absolute magnitude of impedance.

Adenosine Triphosphate↗

Delayed recognition and infection control for tuberculosis patients in the emergency department.

STUDY OBJECTIVE: The recent increase in tuberculosis (TB) cases may have an important effect on emergency department infection-control measures. We describe infection-control interventions for TB patients admitted through the ED and hypothesize that ED suspicion of TB is associated with more rapid isolation and treatment. DESIGN: Retrospective chart review. SETTING: The ED of a 400-bed urban, university-affiliated county hospital. PARTICIPANTS: Fifty-five patients with TB culture-positive and acid-fast bacillus stain-positive respiratory specimens who were evaluated in the ED during 1991 and 1992. RESULTS: We identified cases from the mycobacteriology log. Demographic and historical data and time elapsed before initiation of infection-control measures and TB therapy were recorded. We assessed the relationships of individual clinical findings and the ED presumptive diagnosis of TB (predictor variables) to time elapsed before isolation and therapy (outcome variables) with the log-rank test. The median time (interquartile range) from ED registration to isolation was 8 hours (range, 3 to 13 hours). An ED presumptive diagnosis of TB was made in 71% of cases and was significantly associated with shorter time elapsed before isolation (5 hours [range, 2 to 10 hours] versus 21 hours [range, 11 to 111 hours]; P < .001) and less time elapsed before therapy (12 hours [range, 9 to 22 hours] versus 128 hours [68 to 374 hours]; P < .001). We found TB exposure, radiographic changes typical of TB, absence of HIV risk factors, presence of cough, and sputum production to be associated with more rapid isolation. CONCLUSION: Among patients with active pulmonary TB in the ED, TB is often unsuspected and isolation measures are often not used. ED suspicion of TB is associated with more rapid isolation and treatment.

Adolescent↗

The pattern of neutral molecular variation under the background selection model.

Stochastic simulations of the infinite sites model were used to study the behavior of genetic diversity at a neutral locus in a genomic region without recombination, but subject to selection against deleterious alleles maintained by recurrent mutation (background selection). In large populations, the effect of background selection on the number of segregating sites approaches the effect on nucleotide site diversity, i.e., the reduction in genetic variability caused by background selection resembles that caused by a simple reduction in effective population size. We examined, by coalescence-based methods, the power of several tests for the departure from neutral expectation of the frequency spectra of alleles in samples from randomly mating populations (Tajima's, Fu and Li's, and Watterson's tests). All of the tests have low power unless the selection against mutant alleles is extremely weak. In Drosophila, significant Tajima's tests are usually not obtained with empirical data sets from loci in genomic regions with restricted recombination frequencies and that exhibit low genetic diversity. This is consistent with the operation of background selection as opposed to selective sweeps. It remains to be decided whether background selection is sufficient to explain the observed extent of reduction in diversity in regions of restricted recombination.

Animals↗

The effect of deleterious mutations on neutral molecular variation.

Selection against deleterious alleles maintained by mutation may cause a reduction in the amount of genetic variability at linked neutral sites. This is because a new neutral variant can only remain in a large population for a long period of time if it is maintained in gametes that are free of deleterious alleles, and hence are not destined for rapid elimination from the population by selection. Approximate formulas are derived for the reduction below classical neutral values resulting from such background selection against deleterious mutations, for the mean times to fixation and loss of new mutations, nucleotide site diversity, and number of segregating sites. These formulas apply to random-mating populations with no genetic recombination, and to populations reproducing exclusively asexually or by self-fertilization. For a given selection regime and mating system, the reduction is an exponential function of the total mutation rate to deleterious mutations for the section of the genome involved. Simulations show that the effect decreases rapidly with increasing recombination frequency or rate of outcrossing. The mean time to loss of new neutral mutations and the total number of segregating neutral sites are less sensitive to background selection than the other statistics, unless the population size is of the order of a hundred thousand or more. The stationary distribution of allele frequencies at the neutral sites is correspondingly skewed in favor of rare alleles, compared with the classical neutral result. Observed reductions in molecular variation in low recombination genomic regions of sufficiently large size, for instance in the centromere-proximal regions of Drosophila autosomes or in highly selfing plant populations, may be partly due to background selection against deleterious mutations.

Animals↗

Quality assurance in the emergency department: evaluation of the ECG review process.

STUDY OBJECTIVE: To determine whether the review of emergency department ECGs by cardiologists contributes to the quality of patient care. STUDY DESIGN: We retrospectively analyzed ED ECGs and compared interpretations of the treating emergency physicians with those of the reviewing cardiologists. We then evaluated the ED care of patients with potentially significant ECG abnormalities that were not detected by the treating emergency physicians, as well as the care of patients whose ECGs were "flagged" by the reviewing cardiologists as needing follow-up. SETTING: University hospital. PARTICIPANTS: Four hundred consecutive ECGs obtained on ED patients. MEASUREMENTS AND MAIN RESULTS: Thirty-three of the 400 tracings had undetected potentially significant or critical ECG abnormalities; this adversely affected patient care in two cases. These two tracings were not flagged by the reviewing cardiologists. Thirteen ECGs were flagged by the cardiologists; patient care was not altered in any of these cases. CONCLUSION: Review of ED ECGs by cardiologists did not affect patient care at our institution.

Aged↗

The effect of linkage and population size on inbreeding depression due to mutational load.

Using a stochastic model of a finite population in which there is mutation to partially recessive detrimental alleles at many loci, we study the effects of population size and linkage between the loci on the population mean fitness and inbreeding depression values. Although linkage between the selected loci decreases the amount of inbreeding depression, neither population size nor recombination rate have strong effects on these quantities, unless extremely small values are assumed. We also investigate how partial linkage between the loci that determine fitness affects the invasion of populations by alleles at a modifier locus that controls the selfing rate. In most of the cases studied, the direction of selection on modifiers was consistent with that found in our previous deterministic calculations. However, there was some evidence that linkage between the modifier locus and the selected loci makes outcrossing less likely to evolve; more losses of alleles promoting outcrossing occurred in runs with linkage than in runs with free recombination. We also studied the fate of neutral alleles introduced into populations carrying detrimental mutations. The times to loss of neutral alleles introduced at low frequency were shorter than those predicted for alleles in the absence of selected loci, taking into account the reduction of the effective population size due to inbreeding. Previous studies have been confined to outbreeding populations, and to alleles at frequencies close to one-half, and have found an effect in the opposite direction. It therefore appears that associations between neutral and selected loci may produce effects that differ according to the initial frequencies of the neutral alleles.

Genetic Linkage↗