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T Day

Publications and source records attributed to T Day.

At least 37 records · Page 2Linked to original sources

A generalization of Pontryagin's maximum principle for dynamic evolutionary games among relatives.

We present two theorems that generalize Pontryagin's maximum principle to the setting of dynamic evolutionary games between genetically related individuals. The two theorems correspond to two types of interactions among individuals: patch-structured populations in which individuals locally "play the field" and pairwise interactions. These generalizations can be used in the same way that Pontryagin's maximum principle is used and they are valid for diploid organisms under a single locus, diallelic genetic model. These generalizations involve an interesting, dynamic version of Hamilton's Rule from inclusive fitness theory. We illustrate how these theoretical results can be applied by modeling the evolution of lifetime resource allocation to growth and reproduction in an annual plant when there is competition for resources among related individuals.

Biological Evolution↗

Competition and the Effect of Spatial Resource Heterogeneity on Evolutionary Diversification.

A model is presented to explore how the form of selection arising from competition for resources is affected by spatial resource heterogeneity. The model consists of a single species occupying two patches connected by migration, where the two patches can differ in the type of resources that they contain. The main goal is to determine the conditions under which competition for resources results in disruptive selection (i.e., selection favoring a polymorphism) since it is this form of selection that will give rise to the evolutionary diversification of resource exploitation strategies. In particular, comparing the conditions giving rise to disruptive selection when the two patches are identical to the conditions when they contain different resources reveals the effect of spatial resource heterogeneity. Results show that when the patches are identical, the conditions giving rise to disruptive selection are identical to those that give rise to character displacement in previous models. When the patches are different, the conditions giving rise to disruptive selection can be either more or less stringent depending upon demographic parameters such as the intrinsic rate of increase and the migration rate. Surprisingly, spatial resource heterogeneity can actually make forms of evolutionary diversification such as character displacement less likely. It is also found that results are dependent on how the resource exploitation strategies and the spatial resource heterogeneity affect the population dynamics. One robust conclusion however, is that spatial resource heterogeneity always has a disruptive effect when the migration rate between patches is low.

Journal Article↗

Sexual selection and the evolution of costly female preferences: spatial effects.

Models of Fisher's runaway process show that if there is a cost to female preference, no preference or male trait exaggeration will evolve. Surprisingly, this is true no matter how small the cost, which reveals that these models of Fisher's process are structurally unstable (Bulmer 1989). Here a model of Fisher's runaway process is presented to demonstrate that costly female preference evolves very easily when space is explicitly included in the model. The only requirement is that the optimal male phenotype changes across the species' range. The model shows that the spatial average of the female preference and male trait reach an evolutionary equilibrium that is identical to those of nonspatial models, but that the preference and male trait can deviate greatly from these averages at any point in space. For example, if random mating results in the lowest cost to females, then at equilibrium the spatial average preference will be zero. Nevertheless, there will be some locations at which females prefer males with larger ornaments and others where they prefer males with smaller ornaments. Results also show that the structural instability of nonspatial models of Fisher's process is less of a problem in spatial models. In particular, many of the main qualitative features of cost-free spatial models of Fisher's process remain valid even when there are small costs of female preference. Finally, the model shows that abrupt changes in the optimal male phenotype across space can result in an amplification of this pattern when preference has a small cost, but it can also result in a pattern similar to reproductive character displacement. Which of these occurs depends on the magnitude of the cost of female preference. This suggests that some patterns of reproductive character displacement in nature might be explained simply by sexual selection rather than by hybrid dysgenesis and reinforcement.

Animals↗

Screening for a prothrombotic diathesis in patients attending family planning clinics.

AIMS: 1. To determine the frequency of prothrombotic markers in young women seeking a new or a repeat prescription of the oral contraceptive pill and perceived to be at high risk of thrombosis. 2. To assess cost-effectiveness of thrombophilia testing within this population. 3. To determine the frequency of acquired activated protein C (APC) resistance. METHODS: Results of thrombophilia testing were retrospectively reviewed on 220 consecutively referred patients' plasmas. Women tested were clients attending local family planning clinics for a new or repeat contraceptive prescription. Samples for testing were collected by the Community Laboratory Service. Investigations included: antithrombin III (AT III), protein C, protein S, APC resistance, factor V Leiden mutation analysis and anti-cardiolipin antibodies. RESULTS: Abnormalities were detected in 35 (15.9%) of the 220 women tested. No patient had all tests performed. The most frequently detected abnormality was an increased APC resistance in 6.8% of the women tested. Three of the 13 patients with an abnormal APC resistance had a discrepancy between the low APC ratio and a negative mutation analysis result for factor V Leiden, suggesting acquired APC resistance. Deficiency of protein C was found in 1.2% (of 162), protein S in 2.0% (of 140), antithrombin III in 0.6% (of 159). Low-titre anti-cardiolipin antibodies were detected in 13.9% of this group (115 tested). CONCLUSIONS: The frequency of abnormal thrombophilia markers detected in this cohort of young women is not significantly different from that seen in a control population. This low incidence suggests that testing has been applied on a population screening basis, rather than preselecting a high-risk group. Thrombophilia screening in this patient group cannot be justified when the clinically relevant end-point is death from pulmonary embolism. The cost of preventing one fatal pulmonary embolism arising as a consequence of screening for activated protein C resistance due to the commonly occurring factor V Leiden is a minimum $25,000,000. This compares very unfavourably with the estimated cost per life saved in the National Breast Screening Programme.

Activated Protein C Resistance↗

Plasma von Willebrand factor and intestinal ischaemia-reperfusion injury in rats.

The purpose of this study was to determine whether plasma von Willebrand factor concentrations are correlated with the degree of intestinal ischaemia-reperfusion injury. Forty-six anaesthetised adult Wistar rats were divided into five groups. The sham-operated group (S, n=10) had laparotomy and isolation of the superior mesenteric artery without clamping. Three ischaemia-reperfusion groups (n=10 in each) had clamping of the superior mesenteric artery for 15, 30, and 45 minutes, respectively, and reperfusion for 15 minutes. A control group (C, n=6) had direct puncture of the heart to sample blood. Mean arterial pressure was measured continuously. Blood was collected at the end of the study to measure von Willebrand factor. The small bowel injury was graded histologically. There was a significant systemic hypotension after declamping in all ischaemia-reperfusion groups, which had a high negative correlation with the histological score (R=-0.46, F=10.1, p<0.003, simple linear regression). Plasma von Willebrand factor was significantly elevated in the three ischaemia-reperfusion groups compared with the control group but not significantly different from the sham-operated group (mean von Willebrand factor concentration (SEM): 156 (29), 283 (29), 295 (25), 381 (44), and 366 (40)% in C, S, ischaemia-reperfusion 15, ischaemia-reperfusion 30, and ischaemia-reperfusion 45 groups, respectively). The concentration of von Willebrand factor was not correlated to the histological score (R=0.22, F=1.83, p<0.2) or the degree of hypotension after the removal of the clamp (R=-0.22, F=1.8, p<0.2, simple linear regression). This study shows that von Willebrand factor concentration does not correlate with the degree of intestinal ischaemia-reperfusion injury. It is unlikely that von Willebrand factor can be used as a predictor of disease severity.

Animals↗

Combined-modality therapy for locoregionally advanced head and neck cancer.

Traditionally, treatment for locally advanced resectable head and neck cancer has been surgical resection followed by postoperative radiation. In unresectable patients, primary radiation has been the mainstay of treatment. In an attempt to improve local control and survival, chemotherapy has been investigated as an adjunct to locoregional treatment. Induction or adjuvant chemotherapy in combination with primary surgical resection has failed to demonstrate an improvement in either local control or survival. Induction chemotherapy followed by radiation therapy is an acceptable alternative to surgical resection for organ preservation. A randomized trial in patients with advanced oropharyngeal carcinoma and another in advanced nasopharyngeal carcinoma have shown an improvement in survival with the use of concomitant chemotherapy and radiation compared to radiation alone. Other prospective randomized trials as well as three meta-analyses also demonstrate improved survival with the addition of concomitant chemotherapy for locally advanced disease. Newer chemotherapeutic agents are currently under investigation, particularly those with radiosensitizing properties. Chemotherapy as part of primary therapy, however, should be used judiciously, and should be based on an assessment of the potential risks and benefits to each patient.

Antineoplastic Combined Chemotherapy Protocols↗

Accuracy of blood loss determination by health care professionals.

Patients undergoing surgery will likely experience some degree of blood loss. There is much literature examining effects of blood loss, but little was found that examined accuracy of estimation of blood loss. The research question for this study was: How accurate are surgical health care professionals in their estimations of blood loss? This study was a pre-experimental between-subject design that used a convenience sample of 85 volunteers who worked in the surgical and postsurgical units of a rural southern 450-bed hospital. The participants viewed 1 of 3 randomly chosen samples of laparotomy pads with variable amounts of blood and saline. Only the researchers knew the exact amount contained on the pads. The variables that were examined and were compared included the professional group, years of experience in surgery or the postanesthesia care unit (PACU), and their estimation of blood loss. Their estimation of blood loss was compared with the actual amount of blood to determine whether one group was more accurate than another statistically and whether increasing years of experience improved accuracy. The statistical tests used were simple and multiple regressions.

Anesthesiology↗

Unifying genetic and game theoretic models of kin selection for continuous traits.

A framework is presented for unifying single locus genetic and game theoretic models of continuous traits under frequency-dependent selection when there are interactions among relatives. This framework serves two purposes. First, it is used to determine how "games between relatives" must be modeled to be genetically valid. There are two commonly employed phenotypic approaches used in this setting, and we demonstrate that, although some of their predictions are always genetically valid, others are invalid in general, and this is true for both haploid asexual and diploid sexual organisms. In particular, we show that both approaches obtain the correct equilibrium and convergence stability conditions, but neither obtains the correct condition for evolutionary stability. Unlike earlier results for discrete trait matrix games (Hines & Maynard Smith, 1979), there is no simple correspondence between phenotypic and genetic predictions, and we provide two examples to illustrate this point. It is possible however, to obtain these earlier results within the present setting by restricting attention to a particular class of fitness functions. These results demonstrate that, even when selection is weak, phenotypic models can fail if fitness is frequency-dependent. The second purpose is to determine when population mean inclusive fitness effect provides an adaptive topography in games between relative. Our results show that the fitness function must have a special form for this to be true, and this form differs between haploid and diploid organisms.

Animals↗

Chromosomal drive and the evolution of meiotic nondisjunction and trisomy in humans.

Trisomy is a genetic abnormality of considerable medical importance. The most familiar example is trisomy 21, which causes Down Syndrome [Cummings, M. R. (1988) Human Heredity: Principles and Issues (West Publishing Company, New York)]. In a classic paper, Axelrod and Hamilton [Axelrod, R. & Hamilton, W. D. (1981) Science 211, 1390-1396] offered a chromosomal drive (CD) hypothesis based on the game iterated prisoner's dilemma (IPD) to explain the evolution of an increased frequency of trisomic pregnancies with maternal age. In this paper we explore this hypothesis and its predictions in detail. On closer examination we find that IPD does not provide an adequate model for the CD hypothesis. Therefore, we develop a more suitable model and explore the conditions necessary for it to explain maternal age-dependent trisomy. Our results demonstrate that a relationship between the decay of a female's reproductive potential and chromosomal drive must exist for the CD hypothesis to work. With appropriate parameter values, a comparison of model predictions with empirical estimates for the age-dependence of trisomy reveals a striking correspondence. We point out a close correspondence between other predictions made by the CD hypothesis and empirical observations, as well.

Animals↗

High-dose paclitaxel, cyclophosphamide, and cisplatin with autologous hematopoietic progenitor-cell support: a phase I trial.

PURPOSE: To determine the maximal-tolerated dose (MTD) of paclitaxel in combination with high-dose cyclophosphamide (CPA) and cisplatin (cDDP) followed by autologous hematopoietic progenitor-cell support (AHPCS). PATIENTS AND METHODS: Forty-nine patients with poor-prognosis breast cancer, non-Hodgkin's lymphoma (NHL), or ovarian cancer were treated with escalating doses of paclitaxel infused over 24 hours, followed by CPA (5,625 mg/m2 intravenously over 1 hour in three divided doses) and cDDP (165 mg/m2 intravenously as a continuous infusion over 72 hours) and AHPCS. Pharmacokinetic measurements for each drug were performed. RESULTS: Dose-limiting toxicities were encountered in two patients at 825 mg/m2 of paclitaxel; one patient died of multiorgan failure that involved the lung, CNS, and kidneys, and the other developed grade 3 respiratory, CNS, and renal toxicity, which resolved. The MTD of this combination was determined to be paclitaxel 775 mg/m2, CPA 5,625 mg/m2, and cDDP 165 mg/m2 followed by AHPCS. Sensory polyneuropathy and mucositis were prominent toxicities, but both were reversible and tolerable. The pharmacokinetics of paclitaxel correlated significantly with the severity of mucositis (P < .001) and peripheral neuropathy (P < .00004). Eighteen of 33 patients (54%) with measurable, heavily pretreated metastatic breast cancer achieved a partial response (PR). Responses were also observed in patients with NHL (four of five patients) and ovarian cancer (two of two). CONCLUSION: It is possible to escalate the dose of paclitaxel to 775 mg/m2 in combination with 5,625 mg/m2 of CPA, 165 mg/m2 of cDDP, and AHPCS. An encouraging response rate in poor-prognosis patients with breast cancer, NHL, and ovarian cancer warrants further study.

Adult↗

Use of P-32 in stage III epithelial carcinoma of the ovary.

From 1982 through 1989, 56 patients with Stage III epithelial carcinoma of the ovary received intraperitoneal chromic phosphate following chemotherapy and second look (52 pts) or as the only postsurgical management (4 pts). Median follow-up was 48 months (range of 24 to 108 months). The 4 patients treated following primary surgery with P-32 without chemotherapy had microscopic abdominal disease (3 pts) or complete reduction of gross abdominal disease (1 pt), and their 5-year survival was 100%. Of the 52 patients treated with P-32 following PAC chemotherapy, 23 were pathologic negative, 15 had microscopic residual, and 14 had gross residual at second look. The 5-year survival following second look was 75% for negative, 48% for microscopic, and 32% for gross residual. There were 4 Grade 3 GI complications (7%). There were no complications in the 38 patients who received the P-32 within 12 hr of surgery. The use of P-32 as an adjuvant for Stage I and II epithelial carcinoma of ovary has been found to be effective in prior GOG trials. We have expanded the selection criteria in patients with Stage III carcinoma to include those who can be surgically reduced to microscopic residual at primary surgery or second look following chemo reduction. Because of multiple prognostic variables affecting survival in Stage III ovarian cancer, a randomized study with control arm would be necessary to draw firm conclusions regarding the effectiveness of P-32. The 5-year survival in this group of patients compares favorably to published reports.

Adult↗

Characteristics of Bacillus cereus related to safe food production.

Thirty Bacillus cereus strains, isolated from different sources, were characterized in relation to safe food production. The minimal growth temperatures of the strains varied from < or = 5 degrees C to 11 degrees C. Generation times at 7 degrees C of strains capable of growing at temperatures < or = 5 degrees C were approximately 8.2 h. The D90 degrees C-values of spores of strains with a minimal growth temperature of 11 degrees C determined in phosphate buffer at pH 7.0 ranged from 4.8 to > 200 min. Strains with the capacity to grow at temperatures < or = 9 degrees C, had a D90 degrees C value ranging from 4.6 to 14 min. Addition of either nisin (250 micrograms/ml) or diacetyl (1500 micrograms/ml) to the heating menstruem at the single concentrations investigated seemed not influence the thermal destruction of spores. Germination of spores of almost all strains occurred in all three media tested (Brain Heart Infusion, rice extract and milk) even at temperatures below the minimal growth temperature. All B. cereus strains tested yielded positive results with a commercial test kit for diarrhoeal enterotoxin. The results indicate that strains with the capacity to grow at temperatures < or = 7 degrees C are not essentially different from those with minimal growth temperatures of > 10 degrees C.

Bacillus cereus↗

An anatomical study of retinal arteriovenous crossings and their role in the pathogenesis of retinal branch vein occlusions.

To elucidate the anatomical features which predispose artery over vein (AV) crossings to be the preferential sites for retinal branch vein occlusions (RBVO), 11 AV and six vein over artery (VA) crossings in 12 eyes from non-hypertensive donors who were aged 35 to 82 years, were studied by light and electron microscopy. At AV crossings the veins were often observed to abruptly alter direction to pass under the artery. Here focal stratification of the vein basement membrane opposite the point of contact with the artery was seen. A focal reduction in the vein lumen occurred at three of 11 AV crossings. In contrast, deviation of the vein, focal basement membrane stratification or focal narrowing was not seen at VA crossings. Both types of crossings had a common adventitial sheath when each vessel was of large calibre. This study demonstrated anatomical features which predispose AV crossings to be the preferential site for venous occlusion.

Adult↗

Complications in the use of intra-abdominal 32P for ovarian carcinoma.

From 1982 through 1989, 94 patients at the University of Louisville with ovarian neoplasm had abdominal instillation of 15 mCi chromic 32P as part of their management. The timing of the 32P was immediately postoperative in 55 patients and delayed greater than 24 hr in 39 patients. This is an analysis of factors contributing to gastrointestinal (GI) complications. GI complications were graded according to RTOG guidelines. There was a total of 11 GI complications grade 3 or worse for an overall incidence of 12%. Factors analyzed include timing of 32P delivery, age, stage, number of previous surgeries, use of Hyskon at surgery, addition of external beam radiation, and subsequent use of chemotherapy. There were significantly fewer complications when 32P was given on the same day as surgery than when 32P administration was delayed more than 12 hr following surgery (4% vs 21%), P = 0.007. This difference held significance when adjusted for the number of previous surgeries, use of Hyskon, external beam radiation, and stage. None of the other factors had a significant effect on complication rate. There have been no incidences of contamination even though 32P instillation in the immediate post-operative period had increased risk of contamination due to wound leakage or reoperation. In our experience, the delivery of 32P in the immediate postoperative period resulted in a significant reduction in abdominal complications.

Actuarial Analysis↗

Intravenous immunoglobulin therapy in the inflammatory neuropathies.

The inflammatory demyelinating polyneuropathies are presumed to be autoimmune diseases and as such have been treated in the past with corticosteroids, plasmapheresis and immunosuppressants. Immunoglobulin infusions represent a fourth treatment with the potential to modify the activity of the immune system in disease states. Limited past experience suggests that both acute inflammatory polyneuropathy and chronic inflammatory demyelinating polyneuropathy may respond to immunoglobulin infusions with minimal morbidity. We here outline our successful experience of this treatment in 5 of 6 patients with inflammatory demyelinating polyneuropathies and review the literature describing its use.

Acute Disease↗