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Results for “balancing selection”

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PubMedDate not supplied

Too much ado about propensity score models? Comparing methods of propensity score matching.

OBJECTIVE: A large number of possible techniques are available when conducting matching procedures, yet coherent guidelines for selecting the most appropriate application do not yet exist. In this article we evaluate several matching techniques and provide a suggested guideline for selecting the best technique. METHODS: The main purpose of a matching procedure is to reduce selection bias by increasing the balance between the treatment and control groups. The following approach, consisting of five quantifiable steps, is proposed to check for balance: 1) Using two sample t-statistics to compare the means of the treatment and control groups for each explanatory variable; 2) Comparing the mean difference as a percentage of the average standard deviations; 3) Comparing percent reduction of bias in the means of the explanatory variables before and after matching; 4) Comparing treatment and control density estimates for the explanatory variables; and 5) Comparing the density estimates of the propensity scores of the control units with those of the treated units. We investigated seven different matching techniques and how they performed with regard to proposed five steps. Moreover, we estimate the average treatment effect with multivariate analysis and compared the results with the estimates of propensity score matching techniques. The Medstat MarketScan Data Base provided data for use in empirical examples of the utility of several matching methods. We conducted nearest neighborhood matching (NNM) analyses in seven ways: replacement, 2 to 1 matching, Mahalanobis matching (MM), MM with caliper, kernel matching, radius matching, and the stratification method. RESULTS: Comparing techniques according to the above criteria revealed that the choice of matching has significant effects on outcomes. Patients with asthma are compared with patients without asthma and cost of illness ranged from 2040 dollars to 4463 dollars depending on the type of matching. After matching, we looked at the insignificant differences or larger P-values in the mean values (criterion 1); low mean differences as a percentage of the average standard deviation (criterion 2); 100% reduction bias in the means of explanatory variables (criterion 3); and insignificant differences when comparing the density estimates of the treatment and control groups (criterion 4 and criterion 5). Mahalanobis matching with caliber yielded the better results according all five criteria (Mean = 4463 dollars, SD = 3252 dollars). We also applied multivariate analysis over the matched sample. This decreased the deviation in cost of illness estimates more than threefold (Mean = 4456 dollars, SD = 996 dollars). CONCLUSION: Sensitivity analysis of the matching techniques is especially important because none of the proposed methods in the literature is a priori superior to the others. The suggested joint consideration of propensity score matching and multivariate analysis offers an approach to assessing the robustness of the estimates.

Confounding Factors, Epidemiologic↗

PubMed1982

X-autosome translocations: cytogenetic characteristics and their consequences.

To define the principal characteristics of X-autosome translocations, the authors present a study of 105 cases, five of which are personal observations. The autosomal pairs 15, 21, and 22 are affected by t(X-Aut) more often than would be expected. The distribution of breakpoints on the X chromosome does not differ significantly from the expected distribution. The analysis of different patterns of inactivation seems to confirm that the inactivation could occur at random, but would be followed by a cellular selection favoring the better genetic balance. An estimate of the incidence of t(X-Aut) is proposed, based upon the conclusions that only one chromosome is susceptible to translocation in meiosis in both males and females and that all affected men will be sterile, as will be 50% of women.

Chromosome Banding↗

PubMed1979

Effects of acute hemodialysis-induced changes in sodium balance on the renin-angiotensin system in renovascular and spontaneously hypertensive rats.

In two-kidney Goldblatt hypertensive, spontaneously hypertensive, and normotensive control rats the activity of the renin-angiotensin system was tested during variation of sodium balance. Acute, exactly calculable and selective changes of total body sodium were achieved by hemodialyzing the conscious rats using dialysate with either high or low sodium content. The activity of the RAS was evaluated by blood pressure response to AT II blockade (saralasin bolus injection; 25 micrograms/kg b.w., i.v.) and the plasma-renin activity. During sodium depletion blood pressure maintenance became renin-dependent; sodium loading caused a decrease of renin-angiotensin activity in renovascular hypertension. A weak direct correlation between deprssor response to saralasin and the PRA could be established in the different sodium-depleted and -loaded states.

Angiotensin II↗

PubMedDate not supplied

State substance abuse and mental health managed care evaluation program.

The articles in this special section of the Journal of Behavioral Health Services & Research (30:1) present results from evaluations of publicly funded managed care initiatives for substance abuse and mental health treatment in Arizona, Iowa, Maryland, and Nebraska. This overview outlines the four managed care programs and summarizes the results from the studies. The evaluations used administrative data and suggest a continuing challenge to structure plans so that undesired deleterious effects associated with adverse selection are minimized. Successful plans balanced risk with limited revenues so that they permitted greater access to less intensive services. Shifts from inpatient services to outpatient care were noted in most states. Future evaluations might conduct patient interviews to examine the effectiveness and quality of services for mental health and substance abuse problems more closely.

Humans↗

PubMed2003

Generation and sequence characterization of a normalized cDNA library from swine ovarian follicles.

Ovulation rate is a major factor determining litter size in swine and is, therefore, a trait of economic importance to the pork industry. The dynamics of follicle development, which in turn are dictated by a balance between follicle recruitment, maturation, selection, and atresia, are a major determining factor of ovulation rate. The role of several genes expressed in the ovaries during these processes has been described, but studies utilizing large-scale genomic approaches have yet to be conducted to examine gene expression in this tissue more globally. We have developed a normalized cDNA library from swine ovarian follicles in various stages of development, ranging from 2.0 to 10.0 mm in diameter, collected from gilts from divergent genetic lines selected for high and low ovulation rates, during the 7 initial days of the follicular phase of the estrous cycle. EST sequences were obtained from 5231 distinct clones derived from this library. In total, 3479 unique sequence clusters were obtained, of which 2661 singletons (76.5%) were observed. BLASTN searches with the primary sequences from the clusters obtained resulted in 1037 sequences not matching (E <1.0(-06) any of the sequences in the nt database (29.8% novelty rate). This resource will facilitate the use of cDNA microarrays in functional genomics studies aiming at unraveling the genetic and physiological mechanisms underlying follicle maturation and ovulation rate in swine.

Animals↗

PubMed2005

Are all calories created equal? Emerging issues in weight management.

The global prevalence of overweight and obesity is growing. Correction of the problem through dietary intervention has been disappointing and has prompted research into variations of diet composition or pattern to promote negative energy balance. Limited research suggests that selected approaches, such as low-carbohydrate diets, augment weight loss and offer an advantage over conventional low-fat diets. This has led to the hypothesis that although in theoretical terms a calorie is a calorie, in practice this is not the case. Support for such views and plausible mechanisms exist. Although any advantage may augment weight management, reported discrepancies between theoretical and observed effects are small. Thus, energy-restricted diets should be based primarily on energy intake and expenditure.

Appetite↗

PubMed1990

Prevalence of seasonal affective disorder at four latitudes.

The Seasonal Pattern Assessment Questionnaire (SPAQ) was mailed to a sample population balanced for sex and randomly selected from local telephone directories in four areas: Nashua, NH, New York, NY, Montgomery County, MD, and Sarasota, FL. On the basis of responses to this questionnaire, prevalence rates of winter seasonal affective disorder (winter SAD), summer seasonal affective disorder (summer SAD), and subsyndromal winter SAD were estimated for the four areas. Rates of winter SAD and subsyndromal SAD were found to be significantly higher at the more northern latitudes, while no correlation was found between latitude and summer SAD. The positive correlation between latitude and prevalence of winter SAD applied predominantly to the age groups over 35.

Adult↗

PubMed1993

Tightening the clinical trial.

Randomized clinical trials adhere more closely to pre-agreed-on protocols than almost any other type of experiment, yet we can tighten up their analysis if we desire. If we convert the analysis into a randomization analysis--where the one set of data is analyzed many times--once as though each acceptable assignment has been employed, we can eliminate any dependence of the analysis on statistical or probabilistic assumptions. To do this effectively when many assignments could be acceptable, we can go to double randomization, in which a subset, usefully kept balanced, of acceptable assignments is selected (perhaps randomly) before data acquisition. If we have one covariate, adjustment for which answers a question that is at least as appropriate, we can easily build on this. Imperfect covariance adjustments can help almost as much as perfect ones. If it is appropriate to work with many covariate(s), it is often desirable to first construct a (few) compound covariate(s) and then work with it (them). Often we can base the coefficients in our compound covariate on the univariate regressions of response on single covariates. Doing this within each arm of the trial and pooling keeps the fitting of the final adjustment unbiased. Since we can prespecify how the compounds are to be calculated and fitted, we can do all this while retaining rigid prespecification. Prespecification, randomization, and intelligent use of covariates combined to make the resulting significance analysis of platinum standard quality. (If we want confidence statements, as we ordinarily should, it may make sense, for technical reasons, to plan for somewhat less than platinum standard quality).

Humans↗

PubMed2005

Reorganization of sleep patterns in severe OSAS under prolonged CPAP treatment.

OBJECTIVE: To evaluate the immediate and long-term recovery processes of sleep and daytime vigilance in patients with sleep apnea syndrome (OSAS) after continuous CPAP treatment. METHODS: Five consecutive polysomnographic (PSG) studies were carried out on 10 male patients with severe OSAS. The first recording (baseline) was accomplished without ventilatory support (N0). The other 4 recordings were carried out during the CPAP titration night (N1), during the second night of treatment (N2), during the third night of treatment (N3), and after 30 days of regular CPAP use (N30). Ten age-balanced healthy male subjects were selected from the Parma Sleep Center database as controls. Respiratory variables, conventional PSG variables, arousals, CAP (cyclic alternating pattern) variables, and daytime function (including MSLT) were quantified. ANOVA followed by post-hoc tests explored the differences between controls and OSAS patients in the different recording conditions (N0, N1, N2, N3, N30). The PSG measures that showed significant ANOVA values were correlated with the MSLT scores. RESULTS: Values of control subjects were recovered by REM sleep, REM latency, subtypes A3 and arousal index during N1, by CAP rate and total arousals during N2, by deep sleep (stages 3 + 4) during N3, by light sleep (stages 1 + 2) during N30. The only measures which remained below control values even after 1 month of sustained treatment were the amount of CAP cycles and A1 subtypes. MSLT scores correlated significantly with CAP rate, deep sleep and arousals. CONCLUSIONS: The changes induced by CPAP treatment do not restore immediately a normal sleep structure, which is re-established with different time scales SIGNIFICANCE: The modifications of sleep patterns and the different adjustments of phase A subtypes allow us to monitor the reorganization of sleep in OSAS patients treated with CPAP and the hierarchy of the mechanisms involved in sleep regulation.

Adult↗

PubMed2006

Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells.

Suppressor of cytokine signaling-3 (Socs-3) negatively regulates the action of various cytokines, as well as the metabolic hormones leptin and insulin. Mice with haploinsufficiency of Socs-3, or those with neuronal deletion of Socs-3, are lean and more leptin and insulin sensitive. To examine the role of Socs-3 within specific neurons critical to energy balance, we created mice with selective deletion of Socs-3 within pro-opiomelanocortin (POMC)-expressing cells. These mice had enhanced leptin sensitivity, measured by weight loss and food intake after leptin infusion. On chow diet, glucose homeostasis was improved despite normal weight gain. On a high-fat diet, the rate of weight gain was reduced, due to increased energy expenditure rather than decreased food intake; glucose homeostasis and insulin sensitivity were substantially improved. These studies demonstrate that Socs-3 within POMC neurons regulates leptin sensitivity and glucose homeostasis, and plays a key role in linking high-fat diet to disordered metabolism.

Animals↗

PubMed2006

Attentional demands of postural control: the ability to selectively allocate information-processing resources.

Most studies have suggested the process of recovering body stability requires information-processing resources, but whether adults have the ability to selectively allocate resources to maintain balance is not known. Using a variable priority dual-task paradigm the present experiment investigated the extent to which young adults are able to shift attention between a postural task and a visual spatial memory task. Our results demonstrated a significant difference in verbal response time dependent on instructional set (focus on visual spatial memory versus postural task) but no difference in body sway measurement, indicating the ability of young adults to modulate visual spatial memory task, but not postural task focus. This suggests the existence of a hierarchy within attentional tasks with postural stability being a priority to stabilize gaze and head position.

Adult↗

PubMed2002

Unequal group sizes in randomised trials: guarding against guessing.

We cringe at the pervasive notion that a randomised trial needs to yield equal sample sizes in the comparison groups. Unfortunately, that conceptual misunderstanding can lead to bias by investigators who force equality, especially if by non-scientific means. In simple, unrestricted, randomised trials (analogous to repeated coin-tossing), the sizes of groups should indicate random variation. In other words, some discrepancy between the numbers in the comparison groups would be expected. The appeal of equal group sizes in a simple randomised controlled trial is cosmetic, not scientific. Moreover, other randomisation schemes, termed restricted randomisation, force equality by departing from simple randomisation. Forcing equal group sizes, however, potentially harms the unpredictability of treatment assignments, especially when using permuted-block randomisation in non-double-blinded trials. Diminished unpredictability can allow bias to creep into a trial. Overall, investigators underuse simple randomisation and overuse fixed-block randomisation. For non-double-blinded trials larger than 200 participants, investigators should use simple randomisation more often and accept moderate disparities in group sizes. Such unpredictability reflects the essence of randomness. We endorse the generation of mildly unequal group sizes and encourage an appreciation of such inequalities. For non-double-blinded randomised controlled trials with a sample size of less than 200 overall or within any principal stratum or subgroup, urn randomisation enhances unpredictability compared with blocking. A simpler alternative, our mixed randomisation approach, attains unpredictability within the context of the currently understood simple randomisation and permuted-block methods. Simple randomisation contributes the unpredictability whereas permuted-block randomisation contributes the balance, but avoids the perfect balance that can result in selection bias.

Bias↗

PubMed2000

Design, characterisation and preliminary clinical evaluation of a novel mucoadhesive topical formulation containing tetracycline for the treatment of periodontal disease.

This study describes the formulation, characterisation and preliminary clinical evaluation of mucoadhesive, semi-solid formulations containing hydroxyethylcellulose (HEC, 1-5%, w/w), polyvinylpyrrolidine (PVP, 2 or 3%, w/w), polycarbophil (PC, 1 or 3%, w/w) and tetracycline (5%, w/w, as the hydrochloride). Each formulation was characterised in terms of drug release, hardness, compressibility, adhesiveness (using a texture analyser in texture profile analysis mode), syringeability (using a texture analyser in compression mode) and adhesion to a mucin disc (measured as a detachment force using the texture analyser in tensile mode). The release exponent for the formulations ranged from 0.78+/-0.02 to 1. 27+/-0.07, indicating that drug release was non-diffusion controlled. Increasing the concentrations of each polymeric component significantly increased the time required for 10 and 30% release of the original mass of tetracycline, due to both increased viscosity and, additionally, the unique swelling properties of the formulations. Increasing concentrations of each polymeric component also increased the hardness, compressibility, adhesiveness, syringeability and mucoadhesion of the formulations. The effects on product hardness, compressibility and syringeability may be due to increased product viscosity and, hence, increased resistance to compression. Similarly, the effects of these polymers on adhesiveness/mucoadhesion highlight their mucoadhesive nature and, importantly, the effects of polymer state (particularly PC) on these properties. Thus, in formulations where the neutralisation of PC was maximally suppressed, adhesiveness and mucoadhesion were also maximal. Interestingly, statistical interactions were primarily observed between the effects of HEC and PC on drug release, mechanical and mucoadhesive properties. These were explained by the effects of HEC on the physical state of PC, namely swollen or unswollen. In the preliminary clinical evaluation, a formulation was selected that offered an appropriate balance of the above physical properties and contained 3% HEC, 3% PVP and 1% PC, in addition to tetracycline 5% (as the hydrochloride). The clinical efficacy of this (test) formulation was compared to an identical tetracycline-devoid (control) formulation in nine periodontal pockets (>/=5 mm depth). One week following administration of the test formulation, there was a significant improvement in periodontal health as identified by reduced numbers of sub-gingival microbial pathogens. Therefore, it can be concluded that, when used in combination with mechanical plaque removal, the tetracycline-containing semi-solid systems described in this study would augment such therapy by enhancing the removal of pathogens, thus improving periodontal health.

Acrylic Resins↗

PubMed1997

Quantitative aspects of the relationship between the sickle-cell gene and malaria.

The relationship between resistance to Plasmodium falciparum infection and the frequency and distribution of the sickle-cell gene in populations exposed to endemic malaria transmission is reducible to clear and quantifiable terms. In this review, Trevor Jones examines the prediction of gene frequency changes under selective pressure, the selective advantage to the heterozygote (balanced polymorphism) that the sickle-cell gene provides to individuals in areas with malaria transmission, and the relationship between sickle-cell gene frequency and malaria, as measured by, for example, sporozoite rate and basic reproduction rate. He seeks to clarify what one can infer about malaria transmission from an analysis of the distribution and inheritance patterns of the sickle-cell gene and sickle-cell disease and under what circumstances these inferences should be made.

Journal Article↗

PubMed2005

Response to 'No country is an island: comment on the House of Commons report Human Reproductive Technologies and the Law'.

Edgar Dahl supports sex selection, e.g. through separation of X and Y sperm or through PGD. It is argued in this commentary that while such sex selection would seem reasonable for balancing a family (wanting a daughter if one already has a son, or vice-versa), it is likely to lead to skewing of female-male ratios, not only in India where it is already as low as 0.8 in certain parts, but possibly also in Great Britain as male chauvinism is not a thing of the past anywhere.

Female↗

PubMed2001

Picomolar detection limits with current-polarized Pb2+ ion-selective membranes.

Minor ion fluxes across ion-selective membranes bias submicromolar activity measurements with conventional ion-selective electrodes. When ion fluxes are balanced, the lower limit of detection is expected to be dramatically improved. As proof of principle, the flux of lead ions across an ETH 5435 ionophore-based lead-selective membrane was gradually compensated by applying a few nanoamperes of galvanostatic current. When the opposite ion fluxes were matched, and the undesirable leaching of primary ions was eliminated, Nernstian response down to 3 x 10(-12) M was achieved.

Journal Article↗

PubMed1996

A tRNA identity switch mediated by the binding interaction between a tRNA anticodon and the accessory domain of a class II aminoacyl-tRNA synthetase.

Identity elements in tRNAs and the intracellular balance of tRNAs allow accurate selection of tRNAs by aminoacyl-tRNA synthetases. The histidyl-tRNA from Escherichia coli is distinguished by a unique G-1.C73 base pair that upon exchange with other nucleotides leads to a marked decrease in the rate of aminoacylation in vitro. G-1.C73 is also a major identity element for histidine acceptance, such that the substitution of C73 brings about mischarging by glycyl-, glutaminyl-, and leucyl-tRNA synthetases. These identity conversions mediated by the G-1.C73 base pair were exploited to isolate secondary site revertants in the histidyl-tRNA synthetase from E. coli which restore histidine identity to a histidyl-tRNA suppressor carrying U73. The revertant substitutions confer a 3-4 fold reduction in the Michaelis constant for tRNAs carrying the amber-suppressing anticodon and map to the C-terminal domain of HisRS and its interface with the catalytic core. These findings demonstrate that the histidine tRNA anticodon plays a significant role in tRNA selection in vivo and that the C-terminal domain of HisRS is in large part responsible for recognizing this trinucleotide. The kinetic parameters determined also show a small degree of anticooperativity (delta delta G = -1.24 kcal/mol) between recognition of the discriminator base and the anticodon, suggesting that the two helical domains of the tRNA are not recognized independently. We propose that these effects substantially account for the ability of small changes in tRNA binding far removed from the site of a major determinant to bring about a complete conversion of tRNA identity.

Anticodon↗

PubMedDate not supplied

The impact of available experimental data on the prediction of 1H NMR chemical shifts by neural networks.

Two different ways were explored to incorporate new available experimental data into previously trained ensembles of feed-forward neural networks, for the structure-based prediction of (1)H NMR chemical shifts of organic compounds. One approach used the new data as the memory of an associative neural network (ASNN) system. For an independent prediction set of 952 cases, a mean average error of 0.19 ppm was achieved (0.13 ppm for 90% of the cases). This approach advantageously avoids retraining the networks, and the predictions compared favorably with those obtained by available commercial software packages. Excellent predictions could also be achieved by retraining the networks with the new data, but only if the training sets were selected so as to be balanced or if the retraining started with the weights of the previously trained networks.

Magnetic Resonance Spectroscopy↗