Genetic selection strategies: computer modeling

There are four primary factors to consider in genetic selection strategies: 1) accuracy of selection, 2) selection intensity, 3) effective population size, and 4) mating system. Current theory indicates that optimum response to selection is achieved by maximizing the first three factors and using a mating systems that allows optimization of reproductive characteristics in dam lines and production characteristics in sire lines. However, with limited resources, compromises among the first three factors are needed. Simulations are useful for examining those compromises. Unrealistic simplifying assumptions are necessary for analytic theoretical results and thus do not address real world breeding problems. Using simulations, the relationship between selection accuracy, which is increased by use of family selection indices or Best Linear Unbiased Prediction (BLUP), and response to selection was examined. Results show that those procedures place a great restriction on effective population size, which offsets most of their advantage, i.e., there is too little emphasis on effective population size. A revision of the methodology and a reappraisal of the results of selection theory for optimization of genetic response is required. Another relationship that is of fundamental importance in breeding programs is that between selection intensity and effective population size. Analytical results for the additive case have been developed but have never been extended to heterotic traits. A gene level simulation program was developed to examine that relationship. Results show that the optimal selection strategy depends on the trait being selected. For additive traits and in the short term (20 generations), one should maximize selection intensity. For heterotic traits, an intermediate proportion (25% of each sex) gives optimal response. In all breeding strategies, primary attention must be given to the rate of inbreeding, which is increased by increasing either accuracy of selection or selection intensity. Inbreeding reduces response to selection in two ways. First, for both additive and nonadditive traits, inbreeding is a measure of the amount of random genetic drift that has occurred. Genetic drift causes loss of favorable alleles. Once lost, those alleles can never be recovered and thus genetic drift lowers the selection limit. Second, for heterotic traits, inbreeding results in a depression of the mean caused by directional dominance.     

Enhancing versus suppressive effects of stress hormones on skin immune function

Delayed-type hypersensitivity (DTH) reactions are antigen-specific cell-mediated immune responses that, depending on the antigen, mediate beneficial (e.g., resistance to viruses, bacteria, and fungi) or harmful (e.g., allergic dermatitis and autoimmunity) aspects of immune function. Contrary to the idea that stress suppresses immunity, we have reported that short-duration stressors significantly enhance skin DTH and that a stress-induced trafficking of leukocytes to the skin may mediate this immunoenhancement. Here, we identify the hormonal mediators of a stress-induced enhancement of skin immunity. Adrenalectomy, which eliminates the glucocorticoid and epinephrine stress response, eliminated the stress-induced enhancement of skin DTH. Low-dose corticosterone or epinephrine administration significantly enhanced skin DTH and produced a significant increase in the number of T cells in lymph nodes draining the site of the DTH reaction. In contrast, high-dose corticosterone, chronic corticosterone, or low-dose dexamethasone administration significantly suppressed skin DTH. These results suggest a role for adrenal stress hormones as endogenous immunoenhancing agents. These results also show that hormones released during an acute stress response may help prepare the immune system for potential challenges (e.g., wounding or infection) for which stress perception by the brain may serve as an early warning signal.     

Measurement invariance versus selection invariance: Is fair selection possible?

This article shows that measurement invariance (defined in terms of an invariant measurement model in different groups) is generally inconsistent with selection invariance (defined in terms of equal sensitivity and specificity across groups). In particular, when a unidimensional measurement instrument is used and group differences are present in the location but not in the variance of the latent distribution, sensitivity and positive predictive value will be higher in the group at the higher end of the latent dimension, whereas specificity and negative predictive value will be higher in the group at the lower end of the latent dimension. When latent variances are unequal, the differences in these quantities depend on the size of group differences in variances relative to the size of group differences in means. The effect originates as a special case of Simpson's paradox, which arises because the observed score distribution is collapsed into an accept-reject dichotomy. Simulations show the effect can be substantial in realistic situations. It is suggested that the effect may be partly responsible for overprediction in minority groups as typically found in empirical studies on differential academic performance. A methodological solution to the problem is suggested, and social policy implications are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Monaural sound localization: acute versus chronic unilateral impairment

We report that choline acetyltransferase (ChAT) activity and neuronal survival were enhanced in rat septal neurons cocultured with hippocampal neurons. The enhancement of ChAT activity also occurred as a result of the addition of hippocampal conditioned medium (HpCM). When septal neurons from embryonic day 17 (E17) rats were cocultured with hippocampal neurons, ChAT activity was increased 2-fold compared with homogeneous culture of septal neurons. By contrast, no increase in ChAT activity was observed in coculture of septal and neocortical neurons. Treatment with HpCM obtained from cultured E19 rat hippocampal neurons enhanced the ChAT activity of E17 rat septal neurons. The enhancement of ChAT activity caused by coculture with hippocampal neurons and that caused by the addition of HpCM were not blocked by the addition of anti-nerve growth factor (NGF) antibody, suggesting that NGF, which is known to increase the ChAT activity of septal neurons both in vivo and in vitro, did not participate in the increase of ChAT activity. These findings indicate that possible target-derived neurotrophic factor(s), other than NGF, from hippocampal neurons enhance(s) the ChAT activity of septal neurons.     

Learner control versus program control as adaptive strategies for selection of instructional support on math rules.

124 undergraduates completed a self-paced lesson on math rules in which a number of supporting examples was adapted to pretest scores through program control, selected through learner control, or kept constant (nonadaptive). In a 4th treatment, the nonadaptive program was presented through lecture. On immediate and delayed tests of achievement, program control means were consistently highest while learner control means were lowest. Nonadaptive support and lecture treatments produced comparable, middle-range outcomes. Interaction patterns suggested increasing advantages of program control over learner control both across retention intervals and as subject-entry ability decreased. Results support the achievement–treatment interaction framework while elucidating possible advantages of program controlled adaptation for applied individualization models, such as the Keller Plan. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Viral myocarditis: balance between viral infection and immune response

Myocarditis is an inflammatory disorder of the heart muscle, and is often underdiagnosed in clinical practice. It presents more dramatically in the young with acute heart failure and more insidiously in adults with chronic dilated cardiomyopathy. The etiology is most often viral in North America, with a wide spectrum of natural history. The majority of patients recover spontaneously, but those with persistent ventricular dysfunction face a 20% one-year mortality. Myocarditis initiates as viral disease, and molecular techniques have confirmed viral persistence. The immune response follows as a two-edged sword-both inadequate and excessive immune responses lead to disease. Finally, the myocyte is the target of the above processes, and expresses molecular, cytokine and vascular changes that lead to dilated cardiomyopathy and heart failure. The gold standard for diagnosis still relies on the overly strict Dallas criteria for evaluating myocardial biopsies. Molecular techniques are playing an increasingly important role in both diagnosis and prognosis. Clinical suspicion is still the key towards an early diagnosis. Treatment must be early and persistent-generally supportive initially, with immunosuppression now playing a secondary role in temporizing those with exuberant immune response. Newer treatments for dilated cardiomyopathy such as amlodipine and carvedilol are equally appropriate for postmyocarditis patients. Future treatment may involve specific biological agents, immune therapy, antiviral strategies and molecular gene therapy.     

Neurovisual impairment: a frequent complication of alpha-interferon treatment in chronic viral hepatitis

Following our earlier observation of clinically evident optic tract neuropathy in patients receiving low-dose interferon (IFN) therapy, we prospectively evaluated 53 consecutive patients treated for chronic hepatitis B or C with a median dose of 3 MU of IFN-a2b thrice weekly. Measurements included routine ophthalmologic evaluation and recordings of visual evoked responses (VER), electroretinograms (ERG), visual acuity, and visual fields, before, at the end of IFN treatment, and at follow-up visits. Baseline P100 latencies of VERs (base-VER) were abnormally prolonged in 24 patients (32 of 106 eyes, 30.2%); age was the only significant covariate associated with increased risk for an abnormal base-VER by multiple logistic regression (relative risk [RR] 5.3 per each 5-year increase in age). In 45 patients (74 eyes) with normal baseline P100 latencies, the end-of-treatment VERs (end-VER) were significantly prolonged compared with baseline, becoming abnormal in 11 (15 of 74 eyes, 20.3%) (138.8+/-8.7 vs. 117.7+/-5.2 ms, P < .001). This subgroup had older age (59.1+/-11.0 vs. 47.5+/-15.3, P=.007) and reduced visual sensitivity compared with their own pretreatment measurements (24.5+/-1.6 vs. 23.0+/-1.2db, P=.019). Changes of end-VERs by age had a sigmoid distribution with a steep increase of values beyond the 5th decade (R2=.326, P < .001). In a logistic regression model, significant predictors of abnormal end-VERs were, patients' age (RR 5.6 per each 5-year increase), presence of hepatitis B virus (HBV) infection (RR 15.1 compared with hepatitis C virus [HCV] infection) and serum cholesterol levels above 240 mg% (RR 7.1 compared with values < 240 mg%). Subconjunctival hemorrhages were seen in 2 cases and funduscopic examination revealed cotton wool spots in one other. ERG recordings and the P100 amplitude remained unchanged. After stopping IFN, the treatment-associated neurovisual abnormalities reversed to normal in 7 patients (10 of 15 eyes) and persisted in 5 (5 of 15 eyes, 33.3%) for up to 37 (median 7.3) months observation, all patients remaining clinically asymptomatic. In conclusion, subclinical neurovisual impairment is a frequent, largely unrecognized complication of low-dose IFN therapy, and patients with chronic hepatitis B and older age appear to be most susceptible. This apparently innocuous complication is long lasting, possibly irreversible in some patients, with yet undetermined consequences on visual function.     

Mnemonic versus nonmnemonic vocabulary-learning strategies: Additional comparisons.

The keyword method of vocabulary learning was compared with 5 methods designed to increase semantic processing of the definitions of the vocabulary words. In Exps I–III with 254 undergraduates, recall of the definitions from the vocabulary words was the critical dependent measure, with the keyword method producing greater learning than in any of the semantic-based or control conditions. None of the semantic-based conditions facilitated definition recall relative to a no-strategy control condition. In Exps IV and V with 144 Ss, the keyword method, 2 semantic strategies, and the no-strategy control procedure were compared with respect to associative and response-learning components of vocabulary learning. The keyword method enhanced vocabulary/definition (associative) learning but not definition (response) learning per se. In contrast, the semantic conditions tended to increase nonassociative learning of the definitions. Results bolster the case that the keyword method is a vocabulary-learning procedure superior to semantic-based strategies advocated by reading theorists. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pure versus hybrid: performance implications of Porter's generic strategies

This article identifies the strategic types in the hospital industry based on the hospital's use of Porter's generic strategies in their pure and hybrid forms. The article also examines differences in performance of hospitals across strategic types. Results indicate that hospitals that follow a focussed cost leadership strategy, in general, have superior performance on a variety of performance measures, while hospitals that use a combination of cost leadership and differentiation perform the poorest. Implications of findings for hospital administrators are also discussed.     

Word selection in reading sentences: preceding versus following contexts

A new task, double-word selection, simulated lexical ambiguity by presenting 2 words between which the reader had to choose while reading a sentence shown at 133 or 150 ms/word, following a procedure called rapid serial visual presentation. The double-word pair was presented for less than 100 ms. In immediate recall of the sentence, readers made a correct selection on most trials, both when the relevant context came before the double words and (less accurately) when the relevant context came shortly afterward (Experiments 1 and 2) or with a delay of up to 1 s (Experiment 3). Both words could often be reported if the sentence was stopped one word after the double words (Experiment 2). In Experiment 4, a single function word determined selection between double words differing in syntactic category. The results are consistent with a 2-stage modular interactive model of word perception (M. C. Potter, A. Moryadas, I. Abrams, & A. Noel, 1993) and extend this model to word selection and lexical disambiguation.     

Group selection for adaptation to multiple-hen cages: humoral immune response

A selected line of White Leghorns, which has shown improved survivability and reduced feather loss in large multiple-hen cages, was evaluated for humoral immune response to SRBC under both stressed and unstressed conditions. Three lines of chickens (selected, control, and commercial) were housed in either single- (1 hen) or multiple-hen cages (12 hens, social competition) and subjected to a cold ambient temperature (0 C) at 33 wk of age and to two heating episodes (38 C) at 44 wk of age. Each hen was challenged intravenously with 1 mL of a 7% saline suspension of SRBC at the time that cold exposure was initiated. Hens subjected to high ambient temperatures had been exposed previously to a cold temperature, but were not challenged with SRBC until 16 to 18 h following the end of the second heating episode. Exposure to cold caused immunosuppression in single-caged hens, but not in hens in colony cages. Single- vs colony-caged hens of the control environment challenged with SRBC at 33 wk of age had similar primary hemagglutinin responses to SRBC. Hens subjected to heat experienced immunosuppression at 9 and 12 d following challenge to SRBC when compared to the controls. Hens of multiple-bird cages challenged with antigen at 44 wk of age had a significantly lower hemagglutinin response to SRBC than those reared in single-bird cages. The three lines of genetic stock had similar primary hemagglutinin responses to SRBC; the interactions of genetic stock with cage size or environmental temperature were not significant. It was concluded that genetically selecting hens for survival in multiple-hen cages did not affect their humoral immune response to SRBC.     

Serum therapy for radiation-induced impairment of immune resistance to metastasis

The use of serum transfusion to remedy radiation-induced damage to established antitumor resistance was investigated in female C3H mice. The mice, which had been actively immunized against a syngeneic mammary carcinoma, were injected i.v. and s.c. with suspensions of cells from the same tumor and were then given 300 R extensive-field irradiation to the abdomen two times. Tumor cells implanted outside the irradiated area grew better in irradiated mice than in unirradiated controls. Under these experimental conditions, protection could be transferred to radiation-impaired hosts with several injections of cell-free immune serum. Transfers of normal serum provided a detectable but low degree of protection. The corrective effect of serum transfers to radiation-impaired hosts was clearly expressed against pulmonary tumor growth (i.v. challenge), provided the transfusions were started no later than the first day after the injection of the tumor cells. Serum transfusions were ineffective against the growth of tumors implanted s.c. Transfers of serum from hosts carrying large (15 mm) s.c. tumor implants had a negative effect on the resistance of irradiated recipients. The results indicate that humoral resistance factors, both normal and immune, may act against metastatic spread of solid tumors.     

Translational research studies of erbB oncogenes: selection strategies for breast cancer treatment

Effect of indirect moxibustion stimulation on mouse skin was studied by thermal qualitative, biochemical, and histological methods. The maximum temperature change by indirect moxibustion was about 65 degrees C on the skin, and 45 degrees C in the subcutaneous layer. The treatment of indirect moxibustion was found to be associated with the decrease of lipid peroxidation and increase of superoxide dismutase (SOD) in the skin. Histological findings after indirect moxibustion showed an increase in the number of hair mother cells and hypertropy of the cells.     

Human vaginal mucosal immune system: characterization and function

The analysis of 49 fatal cases of venous thromboembolism--VTE (15% of total ambulatory patients number during long observation was performed. The advanced age of patients, multiple risk factors, underlying circulatory and respiratory tract diseases, malignancies, previous episodes of VTE especially with secondary pulmonary hypertension were the most important factors determining fatal prognoses in those patients.     

Exercise and physical health: cancer and immune function

Over the last decade, there has been accumulating epidemiological data suggesting that exercise may decrease the risk of cancer, particularly colon cancer. However, exercise appears unrelated to rectal cancer risk. With regard to other cancers, because physical activity can alter levels of reproductive hormones, investigators have hypothesized that active individuals should experience decreased incidence of breast or prostate cancer. The better conducted studies suggest that exercise may reduce the risk of developing breast cancer. However, the epidemiological data on prostate cancer have been inconsistent. Meanwhile, data on other site-specific cancers have been sparse. An exciting and emerging body of research has suggested that exercise, at least in moderate amounts, can enhance the human immune system. Theoretically, then, this provides a further biological basis for expecting an inverse relationship between physical activity and cancer risk. However, the changes seen in immune function tend to be transient in nature; thus, the physiological significance with respect to cancer development is uncertain. Preliminary data also suggest that exercise may be beneficial for cancer patients by improving the quality of life and enhancing immune function. Although promising, this needs more careful research. Again, it is unclear whether the enhanced immune function is of any clinical significance in retarding the spread of cancer that has already developed. Finally, with regard to URTIs, moderate exercise appears to decrease the risk of this infection, although high-endurance exercise may increase the risk. This finding parallels the changes seen in the immune system in response to exercise and comes as no surprise, as the immune system also regulates susceptibility to infections.     

Effect of pentachlorophenol on immune function

The organochlorine compound, pentachlorophenol, was evaluated for effects on immune system function in male Fisher 344 rats. Pentachlorophenol was prepared in an olive oil vehicle and was administered by oral gavage twice weekly for 28 days at a dose of 2.0 mg/kg per treatment. Exposure to pentachlorophenol increased body weight gains (P=0.024) during the treatment period. Liver (P=0.034) and kidney (P=0.012) body weight ratios were also increased. Pentachlorophenol exposure enhanced T-lymphocyte blastogenesis induced by concanavalin A (Con A)(P=0.0001) and phytohemagglutinin (PHA)(P=0.048) evaluated using stimulation indices. Corresponding B-lymphocyte blastogenesis induced by lipopolysaccharide/dextran (LPS/dex)(P=0.0034) was also enhanced by pentachlorophenol exposure. Pentachlorophenol suppressed the antibody response against sheep red blood cells (SRBCs) by 39% when the response was expressed per viable spleen cell (P=0.006). This suppression was not evident when the response was expressed per spleen (P=0.22), suggesting that a compensatory mechanism or extramedullary splenic hemopoiesis was occurring minimizing the overall impact on humoral immunity. The enhanced B- and T-lymphocyte blastogenesis may also reflect compensatory or hemopoietic activity. Pentachlorophenol exposure had no effect on peritoneal macrophage phagocytosis (P=0.31) or lymphocyte cell surface antigen expression. The observed alterations in lymphocyte blastogenesis and humoral immunity subsequent to pentachlorophenol exposure do not appear to be associated with phagocytosis or lymphocyte cell surface antigen expression.     

Cell mediated immune response in chronic liver diseases: schistosomal, viral and neoplastic

Cell mediated immune response (CMIR) was studies in 120 patients having chronic liver diseases. Patients were divided into 6 groups, (20 each). (1) Early hepatosplenic Schistosomiasis. (EHSS), (2) Late hepatosplenic Schistosomiasis. (LHSS), (3) Hepatosplenic Schistosomiasis with hepatitis B and/or C infections, (4) Hepatitis B virus cases. (HBV), (5) Hepatitis C virus cases (HCV), (6) Hepatocellular carcinoma cases. (HCC). Twenty within normal subjects taken as controls. Laboratory investigations revealed significant esinophilia in patients of group (1), haemoglobin level was significantly reduced in patients of group (1, 2, 3, & 6), serum albumin was significantly reduced in group (2). The percentage of positivity of skin testing using purified protein derivative, ranged between 10% of patients with LHSS, HBV, HCC and HSS with HBV and/or HCV, 20% of patients with HCV and 25% of patients with EHSS. Percentage of positivity in control group was 100%. The mean diameter of delayed intradermal reaction (2.2 +/- 0.5-6.1 +/- 2.1 mms.) was significantly lower in patients than controls. The response of lymphocyte transformation test to phytohaemmagglutinin was significantly lower in patients when compared to controls. The association of HBV and/or HCV with hepatosplenomegaly was accompanied with a marked depression in cell mediated immune response. Anaemia, hypoalbuminemia and nutritional status of the patients with chronic liver diseases play a major role in the suppression of cell mediated immune response.     

Rule selection versus rule execution in preschoolers: An error-detection approach.

In 2 experiments, an error-detection approach was used to determine whether 3-year-olds' perseverative errors on the postswitch phase of the Dimensional Change Card Sort (DCCS) are due to lack of response control or representational inflexibility. In Experiment 1, 3-, 4-, and 5-year-olds watched a puppet sort perseveratively on the postswitch phase and evaluated its responses. Most 4- and 5-year-olds detected the puppet's perseverative errors, whereas most 3-year-olds failed to do so despite detecting errors on a simpler card sort. Experiment 2 revealed that 3-year-olds who failed to correctly evaluate the puppet's behavior tended to fail their own DCCS. Results imply that perseveration on the DCCS cannot be attributed to difficulty inhibiting prepotent motor responses. Instead, changes in rule use between 3 and 5 years of age are interpreted in terms of the development of representational flexibility. (PsycINFO Database Record (c) 2010 APA, all rights reserved)