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PubMed1988

Dialyzer re-use--a multiple crossover study with random allocation to order of treatment.

A multiple crossover research study was used to evaluate the effect of dialyzer re-use on fever, blood leaks, serum urea and creatinine values and symptoms. Each of 6 crossover periods consisted of 4 weeks on either single-use or re-use, 1 week washout, 4 weeks on the alternative treatment and 1 week washout. The re-use consisted of 6 uses of each dialyzer and the washout weeks consisted of 3 single-use sessions. Analysis of paired observations within rather than between patients showed no effects of time (i.e. among crossover periods 1 through 6) or number of re-uses (i.e. among uses 1 through 6). There was no significant difference for temperature change during dialysis, blood leak rate, or the serum urea and creatinine values before the first dialysis of each washout period. There were no differences for symptoms of pruritus, cramps, nausea, headache, chest pain, backache or fatigue. There were no clinical advantages or disadvantages associated with dialyzer re-use.

Cellulose↗

PubMed2001

Vascular Effects of ACE Inhibition Independent of the Renin-Angiotensin System in Hypertensive Renovascular Disease : A Randomized, Double-Blind, Crossover Trial.

-To evaluate whether ACE inhibition and angiotensin II type 1 blockade exert beneficial effects on NO availability independent of their blood pressure-lowering effect, we used a double-blind crossover design to study vascular function in 18 patients with hypertensive renovascular disease during 6 weeks of therapy with enalapril (Ena) and valsartan (Val) compared with non-renin-angiotensin system-mediated treatment with the alpha(1)-blocker doxazosin (Dox). Control measurements were performed in 13 age-matched volunteers. Forearm blood flow was assessed with venous occlusion plethysmography, and serotonin and nitroprusside were used as endothelium-dependent and -independent vasodilators, respectively. Blood pressure was similar during all treatment periods. Serotonin-induced vasodilation was decreased in patients during Dox treatment (n=12) compared with control subjects (n=13) (increase 42+/-20% versus 107+/-65%, P:<0.05). Crossover from Dox to Val (n=6) had no effect on serotonin response (increase 50+/-14%), but crossover to Ena (n=6) caused a significant improvement (increase 79+/-39%, P:<0.05 versus Dox). In an assessment of all patients, serotonin-induced vasodilation during Ena (n=12, increase 75+/-31%) was increased compared with both Val and Dox (43+/-14% and 42+/-20%, respectively; both P:<0.05 versus Ena). The nitroprusside response remained unaltered during all treatment periods. In conclusion, ACE inhibition improves the impaired endothelium-dependent vascular function in patients with hypertensive renovascular disease. This effect is unrelated to blood pressure-lowering or angiotensin II-mediated effects.

Journal Article↗

PubMed2003

General schema theory for genetic programming with subtree-swapping crossover: part I.

This is the first part of a two-part paper which introduces a general schema theory for genetic programming (GP) with subtree-swapping crossover. The theory is based on a Cartesian node reference system which makes it possible to describe programs as functions over the space N(2) and allows one to model the process of selection of the crossover points of subtree-swapping crossovers as a probability distribution over N(4). In Part I, we present these notions and models and show how they can be used to calculate useful quantities. In Part II we will show how this machinery, when integrated with other definitions, such as that of variable-arity hyperschema, can be used to construct a general and exact schema theory for the most commonly used types of GP.

Algorithms↗

PubMed2004

Real-coded memetic algorithms with crossover hill-climbing.

This paper presents a real-coded memetic algorithm that applies a crossover hill-climbing to solutions produced by the genetic operators. On the one hand, the memetic algorithm provides global search (reliability) by means of the promotion of high levels of population diversity. On the other, the crossover hill-climbing exploits the self-adaptive capacity of real-parameter crossover operators with the aim of producing an effective local tuning on the solutions (accuracy). An important aspect of the memetic algorithm proposed is that it adaptively assigns different local search probabilities to individuals. It was observed that the algorithm adjusts the global/local search balance according to the particularities of each problem instance. Experimental results show that, for a wide range of problems, the method we propose here consistently outperforms other real-coded memetic algorithms which appeared in the literature.

Algorithms↗

PubMed1977

Crossover PO2, a measure of the variable effect of increased P50 on mixed venous PO2.

The effect on mixed venous Po2 of a shift to the right in the oxygen hemoglobin equilibrium curve, without a change in either arterial Po2 or oxygen uptake, depends on the difference between the arterial oxygen saturation differences and the venous oxygen saturation differences of the shifted and standard curves. For every rightward-shifted oxygen hemoglobin equilibrium curve there is a Po2, which I call the crossover Po2, at which mixed venous Po2 is the same for the standard and shifted curve. Crossover Po2 depends upon the hemoglobin concentration and the arteriovenous oxygen content difference. I demonstrate that in hypoxemic patients, especially if anemia and shock are present, the arterial Po2 may be less than the crossover Po2; thus, an increased blood P50, the Po2 at oxygen saturation of 50 per cent (pH 7.40, temperature 37 degrees C), cannot increase the mixed venous Po2.

Aged↗

PubMed1992

Treatment of imipramine-resistant recurrent depression, IV: A double-blind crossover study of tranylcypromine for anergic bipolar depression.

OBJECTIVE: Few trials of monoamine oxidase inhibitors (MAOIs) in tricyclic-resistant depression have had double-blind conditions. In the authors' previous double-blind comparison of tranylcypromine and imipramine in anergic bipolar depression, tranylcypromine was significantly more effective. This investigation was a crossover study of nonresponders in the initial study. METHOD: The subjects were 16 outpatients with anergic bipolar depression. Fourteen had not responded to 4 weeks of treatment with at least 30 mg/day of tranylcypromine or 150 mg/day of imipramine, and two patients were crossed over because of intolerable side effects from the initial drug. The crossover medication was prescribed as in the initial double-blind study. RESULTS: Twelve patients were crossed over from imipramine to tranylcypromine; nine of them responded to tranylcypromine. Highly significant improvements were documented on the Hamilton, Beck, and Pittsburgh Reversed Vegetative Symptom Scales. Four patients were switched from tranylcypromine to imipramine, but only one responded. CONCLUSIONS: The high rates of response to tranylcypromine in both the initial and crossover double-blind studies document the efficacy of MAOI treatment for anergic bipolar depression. Moreover, the results further illustrate the utility of MAOIs in tricyclic-resistant depressions.

Adolescent↗

PubMed2001

Pindolol potentiation of paroxetine for generalized social phobia: a double-blind, placebo-controlled, crossover study.

OBJECTIVE: The effectiveness of pindolol as an adjunctive treatment to boost response to selective serotonin reuptake inhibitors (SSRIs) in patients with generalized social phobia was tested. METHOD: A double-blind, placebo-controlled, crossover design was used to compare addition of 5 mg of pindolol t.i.d. or placebo for 4 weeks to a steady paroxetine dose. Subjects were 14 patients with generalized social phobia who were less than "very much improved" on the Clinical Global Impression scale after at least 10 weeks of treatment with a maximally tolerated dose of paroxetine. Changes on the Liebowitz Social Anxiety Scale and the Social Phobia Inventory scores were compared across the two crossover periods. RESULTS: Pindolol was not significantly superior to placebo for augmenting the effects of paroxetine on social anxiety symptoms. None of the 14 subjects was deemed a responder to the pindolol arm of the crossover. CONCLUSIONS: Pindolol was no more effective than placebo in augmenting the effects of SSRI treatment for generalized social phobia.

Cross-Over Studies↗

PubMed1998

A comparative evaluation of femorofemoral crossover bypass and iliofemoral bypass for unilateral iliac artery occlusive disease.

The purpose of this study was to compare the results of extra-anatomic femorofemoral crossover bypass grafting to the anatomic iliofemoral bypass grafting procedure in the treatment of patients with unilateral iliac artery occlusive disease with respect to patency and limb salvage. The records of all patients with unilateral iliac artery disease who underwent revascularization between January 1988 and December 1995 at the University of Iowa Hospitals and Clinics (UIHC) were retrospectively reviewed; 108 patients were identified and divided into two groups. Group I (n=68; male/female=44/24) was composed of all patients who underwent a femorofemoral crossover extra-anatomic bypass. All patients who underwent an iliofemoral anatomic bypass constituted group II (n=40; male/female=24/16). The mean age for group I was 60 years (range 28-87) and for group II, 54 years (range 14-86). The medical risk factors between both groups were comparable. Except for the higher incidence of gangrene in group II the indications for surgery were comparable between both groups. A polytetrafluoroethylene graft was used in 88% of group I patients and in 90% of group II patients (NS). In the remaining patients, an autogenous vein conduit was used. Two patients from group I (2.9%) died in the perioperative period (NS). Graft patency was assessed by clinical evaluation, Doppler-derived ankle/brachial indices, and color duplex imaging. The cumulative primary and secondary patency rates, limb salvage, and patient survival were calculated by use of life table analysis (SE<0.1). The need for simultaneous outflow and inflow procedures at the time of surgery was comparable between both groups. The proportion of patients who underwent further revascularization during follow-up was also comparable. The 5-year primary and secondary graft patency rates were 81.7% and 90.3%, in group I and 61.3% and 80.5% in group II. Although the difference between both groups was not significant there was a tendency toward higher rates with femorofemoral bypass. The 5-year survival rates of 80.3% for group I and 73.3% for group II were comparable. These data suggest that there is no significant difference in the long-term results between the femorofemoral crossover bypass grafts and iliofemoral grafts. Both procedures result in acceptable patency and limb salvage rates. The femorofemoral bypass is, however, more attractive, for it can be performed under local anesthesia if needed and does not involve the creation of the retroperitoneal incision necessary with the iliofemoral bypass.

Adolescent↗

PubMed1994

Review of nonparametric methods for the analysis of crossover studies.

This paper reviews nonparametric methods for the analysis of crossover studies. Primary attention is given to crossover studies to compare two treatments for a response variable that has a metric measurement level. For this situation, one can often test hypotheses or obtain confidence intervals for parameters of interest by applying well known univariate nonparametric rank methods (e.g., the Wilcoxon rank sum test, or the Wilcoxon signed rank test) to appropriately specified functions of the data. Related extensions are also available, to some degree, for crossover studies to compare more than two treatments or those for which the measurement level of the response variable is ordinal or has a censored time-to-event nature. Methods for several specific situations along these lines are discussed in terms of principles with potentially broader applicability. Several examples are provided to illustrate the performance of some of the methods.

Confidence Intervals↗

PubMed2005

Line bisection and rebisection: the crossover effect of space location.

OBJECTIVE: To investigate the relationship between the bisection test and the severity of behavioral hemineglect and to verify if this test can predict the behavioral hemineglect. METHODS: Thirty stroke patients with left hemiparesis were divided into 4 groups according to the Catherine Bergego Scale, which assessed the behavioral hemineglect: severe unilateral neglect (UN), moderate UN, mild UN, and lack of UN. Eleven healthy subjects served as age-matched control subjects. In the bisection test, 18 lines were presented on the left, middle, and right of an A4 paper, respectively. The subjects were asked to place a short cross mark in the exact middle point of each line on the paper using their right hand. The middle 6 lines in the above bisection test were extracted on another sheet of A4 paper for the rebisection test. The subjects were asked to divide a line into 4 segments by successive bisections. The proportion of the right part to the length of line for bisecting was calculated. RESULTS: In the bisection test, the main effect of space was significant in every group except the mild neglect group. The crossover effect of space location was found in the severe UN group, the group without UN, and the controls. In the severe UN group, the patients bisected the left and middle lines with rightward bias (<50%) but bisected the right lines with leftward bias (>50%). In the group without UN and the controls, the subjects bisected the left lines with leftward bias (>50%) but bisected the middle and right lines with rightward bias (<50%). Almost the same results were seen in the rebisection test. CONCLUSIONS: This study showed that if the spatial crossover effect occurred in the right space condition, it was strongly supported that this patient had moderate to severe behavioral hemineglect. The crossover effect of the space location was explained by a new model.

Activities of Daily Living↗

PubMed2000

Tourette's syndrome improvement with pergolide in a randomized, double-blind, crossover trial.

OBJECTIVE: To determine whether pergolide, a mixed D1-D2-D3 dopamine agonist, is efficacious and safe in the treatment of children with Tourette's syndrome. BACKGROUND: Neuroleptics, which block dopamine transmission, are currently used for treatment of children with severe tics, but major side effects and limited efficacy reduce clinical utility. Prior open-label reports of pergolide suggest potential benefit. METHODS: The authors enrolled 24 children age 7 to 17 years with Tourette's disorder, chronic motor tic disorder, or chronic vocal tic disorder by Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria, plus severity criteria on the Yale Global Tic Severity Scale (YGTSS) of > or =20, in a double-blind, placebo-controlled, crossover study. Children were randomized to receive either placebo or up to 300 microg/day pergolide for the first 6-week treatment period, with a 2-week placebo washout, followed by crossover to the alternate treatment. The primary outcome measure was tic severity assessed by YGTSS. RESULTS: Compared with placebo treatment, pergolide treatment was associated with significantly lower YGTSS scores (42.0 +/- 20.4 versus 23.5 +/- 18.7; F = 12.0, df = 1, 17, p = 0.0011). No patient had a serious adverse event and pergolide was well tolerated. CONCLUSIONS: In this randomized, placebo-controlled, crossover trial, pergolide appeared to be a safe and efficacious treatment for Tourette's syndrome in children.

Adolescent↗

PubMed2004

Determining minimum alveolar anesthetic concentration of halothane in rats: the effect of incremental change in halothane concentration and number of crossovers.

Computer simulations for the technique of estimating minimum alveolar anesthetic concentration (MAC) in patients (quantal design) suggest that incremental concentration changes and the number of crossovers affect MAC. We hypothesized that these variables may also apply to estimating MAC in rats (bracketing design). This study tested that hypothesis and also examined whether these variables might mask differences in MAC between groups in which MAC might be expected to differ (pregnant [P] versus nonpregnant [NP]). There were 2 cohorts (n = 27 and n = 30 rats). Each cohort included NP females, females in early P, and females in late P. MAC was tested by using an incremental concentration change of 0.20% and one within-subject crossover in the first cohort and by using an increment size of 0.10% and four crossovers in the second cohort. MAC was statistically significantly increased in the three groups in the second cohort (NP, 1.16 +/- 0.12; early P, 1.14 +/- 0.10; late P, 1.07 +/- 0.10; mean +/- sd) compared with values in the three comparable groups in the first cohort (NP, 0.95 +/- 0.06; early P, 1.01 +/- 0.09; late P, 0.93 +/- 0.13). Values did not differ among groups within each cohort. Post hoc simulations indicated that up to 36% of the difference between cohorts was due to increment size, with the balance due to experimental factors. Our findings confirmed the hypothesis that increment size affects estimates of MAC when a bracketing design is used.

Anesthetics, Inhalation↗

PubMed2000

Bidirectional case-crossover studies of air pollution: bias from skewed and incomplete waves.

The case-crossover design compares exposures during the period of time of failure with one or more periods when failure did not occur and evaluates the potential excess risk using conditional logistic regression. In this simulation study, we applied several control sampling approaches to control for confounding by various temporal patterns of an exposure variable and evaluated the usefulness of symmetric bidirectional control strategies. We simulated true relative risks (RRs; true ss = 0.001) of deaths of 1.051 per 50-ppb increase of sulfur dioxide and included confounding by right- or left-skewed seasonal waves, linear long-term time trends, or a combination of both. The range of the estimated RRs from symmetric bidirectional control sampling approaches was 1.044 approximately 1. 056 at either a long-term trend or any skewed seasonal wave of SO(2) levels, which indicated the bidirectional control sampling methods would successfully control confounding by design. The simulations with bidirectional sampling, however, show that biases may occur if waves are incomplete (20-43% underestimated RRs). In conclusion, our simulations show that the symmetric bidirectional case-crossover design can substantially control for confounding by linear long-term trends and/or seasonality of an exposure variable by design as well. However, unidirectional control sampling would fail to control confounding by those variations of air pollution. Simulation results also show that even the bidirectional case-crossover design can be biased in a situation where the exposure variable shows incomplete cyclic waves, and therefore it cannot completely control for temporal confounding.

Air Pollution↗

PubMed1999

A case-crossover analysis of air pollution and mortality in Philadelphia.

This study reassessed Schwartz and Dockery's analysis of daily mortality from nonexternal causes among residents of Philadelphia, Pennsylvania, over 8 years, from 1973 to 1980 [American Review of Respiratory Disease 145:600-604 (1992)]. A Poisson regression analysis using the same model found that a 100-microg/m(3) increment in the 48-hr mean concentration of total suspended particulates (TSP) was associated with increased all-cause mortality [rate ratio = 1.069; 95% confidence interval (CI), 1.043-1.096) after adjustment for quadratic trend, season, year, previous day's mean temperature, dew point, winter temperature, and indicators of hot (temperature > 80 degrees F) and humid days (dew point > 66 degrees F). Critics suggested that time-varying factors such as season and day of week were not sufficiently controlled in this analysis and subsequent studies in other locations. We used a conditional logistic regression analysis with a case-crossover design to reanalyze the data, with air pollution in the prior and subsequent weeks to the day of death serving as referent periods. The case-crossover approach controls for season and day of week by design rather than modeling. We found that a 100-microg/m(3) increment in the 48-hr mean level of TSP was associated with increased all-cause mortality [odds ratio (OR) = 1.056; CI, 1.027-1.086) after adjustment for the same weather variables as above. Similar associations were observed for deaths in individuals over 65 years of age (OR = 1.074; CI, 1. 037-1.111) and for deaths due to cardiovascular disease (OR = 1.063; CI, 1.021-1.107). The current case-crossover analysis confirms the general conclusion of the previous Poisson regression analysis of an association of TSP with daily mortality in Philadelphia, Pennsylvania.

Adolescent↗

PubMed2005

REC, Drosophila MCM8, drives formation of meiotic crossovers.

Crossovers ensure the accurate segregation of homologous chromosomes from one another during meiosis. Here, we describe the identity and function of the Drosophila melanogaster gene recombination defective (rec), which is required for most meiotic crossing over. We show that rec encodes a member of the mini-chromosome maintenance (MCM) protein family. Six MCM proteins (MCM2-7) are essential for DNA replication and are found in all eukaryotes. REC is the Drosophila ortholog of the recently identified seventh member of this family, MCM8. Our phylogenetic analysis reveals the existence of yet another family member, MCM9, and shows that MCM8 and MCM9 arose early in eukaryotic evolution, though one or both have been lost in multiple eukaryotic lineages. Drosophila has lost MCM9 but retained MCM8, represented by REC. We used genetic and molecular methods to study the function of REC in meiotic recombination. Epistasis experiments suggest that REC acts after the Rad51 ortholog SPN-A but before the endonuclease MEI-9. Although crossovers are reduced by 95% in rec mutants, the frequency of noncrossover gene conversion is significantly increased. Interestingly, gene conversion tracts in rec mutants are about half the length of tracts in wild-type flies. To account for these phenotypes, we propose that REC facilitates repair synthesis during meiotic recombination. In the absence of REC, synthesis does not proceed far enough to allow formation of an intermediate that can give rise to crossovers, and recombination proceeds via synthesis-dependent strand annealing to generate only noncrossover products.

Animals↗

PubMed2003

A population-based case-crossover and case-control study of alcohol and the risk of injury.

OBJECTIVE: This study investigated the relationship between alcohol and the risk of acute injury, examining both short-term (drinking over a few hours) and long-term exposures (past-month hazardous drinking and current alcohol use disorders). METHOD: The study was a case-crossover and population-based case control study. Cases (N = 2,517; 1,432 men) were injured patients recruited from all three emergency departments in Boone County, Missouri. Each case's alcohol consumption in the 6 hours prior to injury was compared to his or her consumption the day before in a case-crossover analysis. Community controls (N = 1,856; 948 men) were recruited by telephone and matched to cases by age, gender, day of week and hour. Case-control analyses examined recent alcohol consumption (past 6 hours), past-month hazardous drinking and past-year alcohol use disorders. RESULTS: The odds ratios (ORs) for injury associated with short-term alcohol exposure were similar, whether cases were compared with themselves (case-crossover analyses) or with others (case-control analyses). After 1 or 2 drinks in a 6-hour interval, the ORs were 1.8 (95% confidence interval [CI]: 1.3-2.6) and 1.5 (0.96-2.2), respectively. Similar dose-response curves were seen in the two comparisons, with ORs of 6.2 and 3.7, respectively, after 3 or 4 drinks and 9.5 and 13.5 after 5 or 6 drinks. For past-month hazardous drinking, the OR was 1.7 (95% CI: 1.2-2.3). Current alcohol dependence was associated with injury (OR = 1.9; 95% CI: 1.5-2.6), but alcohol abuse was not (OR = 0.9; 95% CI: 0.8-1.1). CONCLUSIONS: Alcohol's effect on injury risk is related more strongly to acute exposure than to measures of long-term exposure. The risk is significant even at low levels of consumption.

Adolescent↗

PubMed2006

The effects of mismatch repair and RAD1 genes on interchromosomal crossover recombination in Saccharomyces cerevisiae.

We have previously shown that recombination between 400-bp substrates containing only 4-bp differences, when present in an inverted repeat orientation, is suppressed by >20-fold in wild-type strains of S. cerevisiae. Among the genes involved in this suppression were three genes involved in mismatch repair--MSH2, MSH3, and MSH6--and one in nucleotide excision repair, RAD1. We now report the involvement of these genes in interchromosomal recombination occurring via crossovers using these same short substrates. In these experiments, recombination was stimulated by a double-strand break generated by the HO endonuclease and can occur between completely identical (homologous) substrates or between nonidentical (homeologous) substrates. In addition, a unique feature of this system is that recombining DNA strands can be given a choice of either type of substrate. We find that interchromosomal crossover recombination with these short substrates is severely inhibited in the absence of MSH2, MSH3, or RAD1 and is relatively insensitive to the presence of mismatches. We propose that crossover recombination with these short substrates requires the products of MSH2, MSH3, and RAD1 and that these proteins have functions in recombination in addition to the removal of terminal nonhomology. We further propose that the observed insensitivity to homeology is a result of the difference in recombinational mechanism and/or the timing of the observed recombination events. These results are in contrast with those obtained using longer substrates and may be particularly relevant to recombination events between the abundant short repeated sequences that characterize the genomes of higher eukaryotes.

Base Pair Mismatch↗

PubMed1990

Crossover in baroreflex pathways controlling renal sympathetic nerve activity.

Experiments were performed to investigate the physiologic significance of the crossover of baroreceptor afferent input to the contralateral nucleus tractus solitarius (NTS) in terms of reflex control of renal sympathetic nerve activity and to determine the physiologic significance of neuronal crossover which may occur beyond the NTS. Experiments were done in 14 alpha-chloralose anesthetized rabbits. Baroreflex control of left renal nerve activity was determined from responses to phenylephrine-induced increases and nitroglycerin-induced decreases in arterial pressure. Under control conditions, the mean regression slope for changes in renal nerve activity (imp/sec/mmHg change in arterial pressure) was -2.2 +/- 0.5. After unilateral NTS lesion (n = 14) the gain of the reflex was -2.4 +/- 0.4 imp/sec/mmHg. Denervation of baroreceptors ipsilateral to the NTS lesion (n = 6) did not alter the regression slope (-2.7 +/- 0.5 imp/sec/mmHg), but interruption of the contralateral carotid and aortic baroreceptor afferent fibers (n = 8) markedly reduced the slope of the linear regression relationship from -2.4 +/- 0.3 to -1.1 +/- 0.3 imp/sec/mmHg. We interpret these data to suggest that baroreceptor afferent input exerts its major reflex influence via the ipsilateral NTS and that there is modest influence exerted by fibers which cross over to the contralateral side. In addition, since we recorded from the left renal nerves and alternated the side of the NTS lesion, we interpret our findings regarding a lesion in only one NTS to suggest that there is crossover in the baroreflex pathway beyond the NTS which permits the NTS on one side to exert an influence on the renal nerves on the contralateral side similar to that seen when the NTSs on both sides are intact.

Animals↗