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Results for “crossover”

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At least 217 records · Page 12Linked to original sources

PubMed2003

[A case-crossover study of ambient air pollution and daily mortality in Shanghai].

OBJECTIVE: Using case-crossover design to estimate the acute effect of ambient air pollution on daily mortality in Shanghai, and to explore the applicability of if in studying the acute health effects of air pollution. METHODS: Case-crossover technique was used to evaluate the relationship between air pollution and daily mortality from June 2000 to December 2001 in Shanghai. The results of the bi-directional control sampling approach were compared with unidirectional approach. RESULTS: The validity of relative risks in case-crossover studies varied greatly depending on the strategy used in control sampling. When a bi-directional six control sampling approach was used an increase of relative risk of non-accident mortality on each 10 micro g/m(3) over a 48-hr moving average of PM(10), SO(2) and NO(2) corresponds to 1.003 (95% CI: 1.001 - 1.005), 1.016 (95% CI: 1.011 - 1.021), and 1.020 (95% CI: 1.012 - 1.027) respectively was seen. CONCLUSION: The results reinforced the deleterious role of current air pollution level on human health in Shanghai, and provided information on the applicability of case-crossover design in studying the acute health effects of air pollution.

Air Pollution↗

PubMed2005

[Study on the significance and application of crossover analysis in assessing gene-environmental interaction].

OBJECTIVE: To examine the significance of crossover analysis in gene-environmental interaction studies. METHODS: Through elaboration of a case-control study on the increased risk of venous thrombosis in oral-conceptive users who were carriers of factor V Leiden mutation, core information from 2 x 4 crossover table were analyzed and compared with stratified analysis and 'case only' study. RESULTS: Different models (additive or multiplicative) in analyzing gene-environmental interaction yielded different results. The result of interaction based on multiplicative model was 1.35 (P > 0.05), compatible with that of stratified analysis and case only study. Calculated by crossover analysis based on additive model, synergy index S(S), attributable proportion of interaction (AP) and relative excess risk of interaction (RERI) appeared to be 3.90, 72.24%, 25.08 (P > 0.05) respectively. CONCLUSION: Crossover analysis should further be applied in gene-environmental interaction studies.

Case-Control Studies↗

PubMed2006

Modeling the impact of variable climatic factors on the crossover of Culex restauns and Culex pipiens (Diptera: culicidae), vectors of West Nile virus in Illinois.

The aim of this study was to model the impact of temperature on the timing of the seasonal shift in relative proportion of Culex restuans Theobald and Culex pipiens L. in Illinois. The temporal pattern of West Nile virus (WNV) and St. Louis encephalitis virus transmission in the midwest exhibits a late summer to early fall peak in activity, which parallels the temporal increase in the abundance of Cx. pipiens. The daily number of egg rafts oviposited by each species has been monitored at multiple surveillance sites in Urbana-Champaign in central Illinois for more than 13 years. The time when the two Culex species are in equal abundance (crossover) varies considerably from year to year. Our investigation of several thermal measures indicated that this variation was related in large part to climatic conditions with warmer (cooler) temperatures correlated to earlier (later) crossover dates. Models based on degree days and the number of days in which the daily maximum temperature exceeded an upper temperature threshold explained more than 60% of the variance in crossover dates. In contrast, models based on the number of days in which the daily minimum temperature exceeded a lower temperature threshold explained no more than 52% of the variance. An evaluation of these models demonstrated that they provide relatively simple and accurate estimates of crossover date from daily temperature data, a necessary component for developing an overall climatic index for the risk of WNV transmission in Illinois.

Animals↗

PubMed1999

Crossover cutting during hamstring fatigue produces transverse plane knee control deficits.

OBJECTIVE: To assess the effects of eccentric work-induced hamstring fatigue on sagittal and transverse plane (axial) knee and ankle biodynamics and kinetics during a running crossover cut directional change (functional pivot shift). DESIGN AND SETTING: A pretest-posttest, single-group intervention experimental design was employed. All data were collected in a biodynamics laboratory. SUBJECTS: Twenty healthy athletic females were trained for 3 weeks in crossover cutting before testing. MEASUREMENTS: Data were sampled during 3 unfatigued and 3 fatigued (20% eccentric isokinetic knee-flexor torque reduction) crossover cut trials. Three-dimensional kinematic and ground reaction-force data were sampled at 200 Hz and 1000 Hz, respectively, and joint moment estimates were calculated. Data were standardized to initial force-plate heelstrike for comparisons of mean differences between conditions using paired t tests with Bonferroni adjustments. Pearson product-moment correlations compared kinematic and eccentric hamstring-torque relationships. RESULTS: During internal rotation phase 1, between heelstrike and impact absorption, mean internal rotation velocity increased by 21.2 degrees /s +/- 114 degrees /s. During internal rotation phase II, mean peak transverse plane knee rotation during propulsion decreased by 3.1 degrees +/- 9 degrees . During internal rotation phase II, mean peak ankle plantar flexor moment onsets occurred 12.7 +/- 53 milliseconds earlier, and this activation demonstrated a moderately positive relationship with the onset of mean peak knee internal rotation during propulsion and a weak negative relationship with mean peak hamstring torque/lean body weight. CONCLUSIONS: The increased knee internal rotation velocity during phase I indicates transverse plane dynamic knee-control deficits during hamstring fatigue. Earlier peak ankle plantar-flexor moments and decreased internal rotation during phase II in the presence of hamstring fatigue may represent compensatory attempts at dynamic knee stabilization from the posterior lower leg musculature during the pivot shift portion of the crossover cut. The weak relationship between decreased hamstring torque/lean body weight and delayed knee internal rotation during propulsion further supports greater dependence on ankle plantar flexors for dynamic knee stabilization compensation.

Journal Article↗

PubMed1995

Interim analyses in 2 x 2 crossover trials.

A method is presented for performing interim analyses in long term 2 x 2 crossover trials with serial patient entry. The analyses are based on a linear statistic that combines data from individuals observed for one treatment period with data from individuals observed for both periods. The coefficients in this linear combination can be chosen quite arbitrarily, but we focus on variance-based weights to maximize power for tests regarding direct treatment effects. The type I error rate of this procedure is controlled by utilizing the joint distribution of the linear statistics over analysis stages. Methods for performing power and sample size calculations are indicated. A two-stage sequential design involving simultaneous patient entry and a single between-period interim analysis is considered in detail. The power and average number of measurements required for this design are compared to those of the usual crossover trial. The results indicate that, while there is minimal loss in power relative to the usual crossover design in the absence of differential carry-over effects, the proposed design can have substantially greater power when differential carry-over effects are present. The two-stage crossover design can also lead to more economical studies in terms of the expected number of measurements required, due to the potential for early stopping. Attention is directed toward normally distributed responses.

Antiemetics↗

PubMed2001

A case-crossover study of occupational traumatic hand injury: methods and initial findings.

BACKGROUND: Acute hand injury is the leading cause of occupational injury treated in United States' hospital emergency departments (e.g., laceration, crush or fracture). To identify risk factors for traumatic hand injuries, we conducted a case-crossover study of transient exposures (e.g., being rushed) for acute occupational traumatic hand injury. METHODS: The case-crossover method, which uses subjects as their own controls, was used to identify risk factors for occupational hand injury. Two hundred and thirty-two subjects were recruited from 17 occupational health clinics in New England and interviewed by telephone a median of 1.2 days after their injury. The a priori hazard period was defined as 10 min before the injury. Two control periods were used: one was 60-70 min prior to the injury (matched-pair interval analysis); the other was the total work-time exposed, on average, in the previous month (usual frequency analysis). RESULTS: In the usual frequency analysis, the relative risk for using malfunctioning or different-from-usual equipment or tools in the hazard period was 25.5 (95% confidence interval = 18.4-35.2). Relative risks were also significantly elevated for performing a task using an unusual work method, doing an unusual task, being distracted, or being rushed. Wearing gloves appeared to be protective (relative risk = 0.8, 95% CI = 0.5-1.2). Matched-pair interval analysis, where appropriate, provided similar findings but had much wider confidence intervals. CONCLUSIONS: This study demonstrates that the case-crossover design is a feasible and efficient method for studying transient risk factors for sudden-onset traumatic occupational hand injury. The usual frequency analysis proved more useful than the match-pair approach to control period selection.

Accidents, Occupational↗

PubMed2001

Electrophysiological study of forearm sensory fiber crossover in Martin-Gruber anastomosis.

Although anatomical studies have shown that a crossover of sensory fibers is not rare in forearm Martin-Gruber median-ulnar anastomosis (MGA), it has been electrophysiologically described only in rare subjects. Using a near-nerve needle technique, the possibility of electrophysiologically detecting a forearm median-ulnar crossover of sensory fibers was investigated in 24 arms of 21 subjects with unilateral or bilateral MGA, by stimulating the fifth digit of the hand and recording along the median nerve. Small-amplitude elbow responses were found in the median nerve in 10 of the 24 arms but, in 9, the responses disappeared after lidocaine block of the ulnar nerve distal to the elbow sulcus, indicating their volume-conducted origin. In one subject with carpal tunnel syndrome and a subclinical ulnar neuropathy at the elbow, the elbow response was not affected by the ulnar block, thus confirming the presence of a sensory anastomosis in the forearm. In another subject with MGA, a clear-cut sensory response was recorded in the median nerve at the elbow by stimulating the fifth digit of the right hand but no anesthetic block was performed, because ulnar responses were absent above the elbow sulcus due to a severe lesion at the elbow. Thus, use of a near-nerve recording technique facilitates recognition of median-ulnar crossover of sensory fibers to the fifth digit, which is, however, uncommon.

Adult↗

PubMed1998

Treatment of refractory myositis: a randomized crossover study of two new cytotoxic regimens.

OBJECTIVE: To assess the clinical usefulness of 2 novel therapies for treatment-resistant myositis. METHODS: Thirty patients with refractory myositis, of whom 25 had an inadequate or no response to previous cytotoxic therapy, were randomized to begin either a combination of weekly oral methotrexate and daily azathioprine (MTX/AZA) or intravenous methotrexate with leucovorin rescue (I.V. MTX) every 2 weeks for 6 months. Crossover to the alternate therapy occurred according to defined rules; evaluations of muscle strength and functional abilities were performed at the beginning, and after 3 and 6 months, of each treatment. RESULTS: Of the 15 patients initially randomized to oral MTX/AZA, 8 improved with oral therapy and 1 improved with I.V. MTX during the crossover period. Of the 15 patients initially randomized to I.V. MTX therapy, 3 improved with the I.V. therapy and 4 with the oral combination during the crossover period. Although the study lacked the power to directly compare both treatments, intention-to-treat analysis showed a trend in favor of those patients who first received oral combination therapy (P = 0.025). There were 0.09 adverse events per patient-month with oral combination therapy and 0.16 per patient-month with I.V. therapy (P = 0.09). CONCLUSION: Combination oral MTX/AZA may benefit patients with treatment-resistant myositis, including those who previously had inadequate responses to either MTX or AZA alone. I.V. MTX with leucovorin rescue may also benefit some patients with refractory myositis.

Administration, Oral↗

PubMed1992

Double-blind, placebo-controlled crossover study of folinic acid (Leucovorin for the treatment of fragile X syndrome.

We conducted a randomized, double-blind, placebo-controlled crossover study of folinic acid therapy (dl-Leucovorin, 15 mg/day) or placebo for males with Fragile X (fra(x)) syndrome. Twenty-one patients were enrolled in the study. The treatment periods were 3 months in length. Patients were followed with chemistry panels and complete blood counts. No differences between placebo and treatment phases were noted in any laboratory parameter. Instruments to measure functioning were the Vineland Adaptive Behavioral Scales, Peabody Picture Vocabulary Test-Revised, Conners Parent and Teaching Rating Scales, the ADD-H: Comprehensive Teacher's Rating Scales (ACTeRS), and a questionnaire designed by the investigators. At the crossover point, 2 parents requested to withdraw from the study because they felt their children had made dramatic gains during the first half of the study and had lost those gains after the crossover point. Both parents had accurately predicted that their sons were receiving folinic acid during the first half of the study. However, no statistically significant differences could be demonstrated between the treatment and placebo phases of the study with any instrument when the results were averaged over the entire cohort. After the conclusion of the study, approximately one-half of the parents believed that their children had benefitted from the folinic acid therapy and elected to continue treatment. Thus far, no significant side effects have been noted from long-term folinic acid therapy so we are offering all Fragile X patients a 3-month trial of medication.

Adolescent↗

PubMed2006

Lack of meiotic crossovers during oogenesis in an apparent 45,X Ullrich-Turner syndrome patient with three children.

A woman with apparent 45,X Ullrich-Turner syndrome was ascertained after the birth of three girls, the last being growth retarded due to a del(X)(p22.11) of grand-paternal origin. In this woman no del(X)-chromosome was detectable in blood by FISH or PCR. Fibroblast cultures from four different biopsies of her skin varied from having 45,X only to mosaic 46,X,del(X) to 46,X,del(X) only. In one fibroblast culture, a few cells with two del(X) chromosomes were found, probably remnants of a paternal dicentric X that caused the condition. Her three daughters were born when she was 29, 31, and 39 years old, respectively, indicating that disomy for the distal half of Xp is not required for normal folliculogenesis. When studying the crossover pattern of her daughters' maternal X-chromosomes, it turned out that one daughter had an X that was exclusively grand-maternal, one daughter lacked crossovers on Xq, and one daughter lacked crossovers on Xp. This suggests that univalent X-chromosomes were present in the Ullrich-Turner patient's primordial egg cells, either because there was only a single X-chromosome present (a 45,X primary oocyte), or because the X-chromosome was a partially or completely unpaired in pachytene, indicating a problem with chromosome association and synapsis formation.

Child, Preschool↗

PubMed2004

On the nature of the plateau in two-step dinuclear spin-crossover complexes.

A remarkable feature of the spin-crossover process in several dinuclear iron(II) compounds is a plateau in the two-step transition curve. Up to now, it has not been possible to analyse the spin state of dinuclear pairs that constitute such a plateau, due to the relative high temperatures at which the transition takes place in complexes investigated so far. We solved this problem by experimentally studying a novel dinuclear spin-crossover compound [[Fe(phdia)(NCS)(2)](2)(phdia)] (phdia: 4,7-phenanthroline-5,6-diamine). We report here on the synthesis and characterisation of this system, which exhibits a two-step spin transition at T(c1)=108 K and T(c2)=80 K, displaying 2 K and 7 K wide thermal hysteresis loops in the upper and the lower steps, respectively. A plateau of approximately 20 K width centred at about 90 K, which corresponds to the 50 % of the spin conversion, separates the two transitions. The composition of the plateau was identified in metastable state after quenching to 4.2 K by means of Mössbauer spectroscopy in an external magnetic field. Such experiments revealed that the plateau consists mainly of [HS-LS] pairs (HS=high spin, LS=low spin) and confirmed the hypothesis that the spin conversion in dinuclear entities proceeds through [LS-LS]<-->[HS-LS]<-->[HS-HS] pairs. The results are discussed in terms of a thermodynamic model based on the regular solution theory adapted for dinuclear spin-crossover compounds.

Journal Article↗

PubMed2004

Readily prepared metallo-supramolecular triple helicates designed to exhibit spin-crossover behaviour.

New dinuclear supramolecular cylinders have been designed to exhibit spin-crossover behaviour, a form of molecular bistability. This has been achieved within the framework of our imine-based approach to supramolecular architecture by switching from pyridylimine systems to imidazolimines. Spin-crossover behaviour is achieved while retaining the simplicity and ease-of-synthesis of our molecular design. The imidazole groups used also introduce additional NH groups that engage in hydrogen-bonding to anions and solvents. In the case of the iron(II) tetrafluoroborate complex this hydrogen bonding links supramolecular cylinders into an extended two-dimensional array. Consistent with this, a sharper spin-crossover transition is observed for this compound than for the corresponding hexafluorophosphate salt. More subtle anion effects are indicated in the perchlorate salt which gives a two-step spin conversion, thereby displaying tristability.

Journal Article↗

PubMed2006

Structural and magnetic resolution of a two-step full spin-crossover transition in a dinuclear iron(II) pyridyl-bridged compound.

A dinuclear iron(II) complex containing the new pyridyl bridging ligand, 2,5-di(2',2''-dipyridylamino)pyridine (ddpp) has been synthesised and characterised by single-crystal X-ray diffraction, magnetic susceptibility and Mössbauer spectral methods. This compound, [Fe(2)(ddpp)(2)(NCS)(4)]4 CH(2)Cl(2), undergoes a two-step full spin crossover. Structural analysis at each of the three plateau temperatures has revealed a dinuclear molecule with spin states HS-HS, HS-LS and LS-LS (HS: high spin, LS: low spin) for the two iron(II) centres. This is the first time that resolution of the metal centres in a HS-LS ordered state has been achieved in a two-step dinuclear iron(II) spin-crossover compound. Thermogravimetric data show that the dichloromethane solvate molecules can be removed in two distinct steps at 120 degrees C and 200 degrees C. The partially de-solvated clathrate, [Fe(2)(ddpp)(2)(NCS)(4)]CH(2)Cl(2), undergoes a one-step transition with an increased transition temperature with respect to the as synthesised material. Structural characterisation of this material reveals subtle changes to the coordination geometries at each of the iron(II) centres and striking changes to the local environment of the dinuclear complex. The fully de-solvated material remains high spin over all temperatures. Interestingly, the solvent can be re-introduced into the monosolvated solid to achieve complete conversion back to the original two-step crossover material, [Fe(2)(ddpp)(2)(NCS)(4)]4 CH(2)Cl(2).

Journal Article↗

PubMed1990

Eukaryotic topoisomerases recognize nucleic acid topology by preferentially interacting with DNA crossovers.

Eukaryotic topoisomerases recognize DNA topology and preferentially react with positively or negatively supercoiled molecules over relaxed substrates. To elucidate the mechanism of this recognition, we examined the interaction of topoisomerases with DNA by electron microscopy. Under all conditions employed, approximately 90% of the bound type I or II enzyme was observed at points of helix--helix juxtaposition on negatively supercoiled plasmids which contained as few as four crossovers. Recognition was independent of torsional stress, as enzyme molecules were also found at crossovers on linear DNA. Since juxtaposed helices are more prevalent in supercoiled compared with relaxed nucleic acids, we propose that eukaryotic topoisomerases I and II recognize underwound or overwound substrates by interacting preferentially with DNA crossovers. This may represent a general mechanism for the recognition of DNA topology by proteins.

Animals↗

PubMed1996

Crossover trials with a binary response: a powerful method despite the carryover effect.

The two-period crossover trial has the evident advantage that, by use of within-patient comparisons, the usual large between-patient variability is not used as a measure to compare treatments. A prerequisite, however, is that the order of the treatments does not substantially influence the outcome of the treatment. Crossover studies with a binary response (such as yes/no or present/absent), although widely used for initial screening of new compounds, have not previously been studied for such order effects. This study uses a mathematical model based on standard statistical tests to study to what extent such order effects, here identical to carryover effects, may reduce the power of detecting a treatment effect. It is concluded that, despite large carryover effects, the crossover study with a binary response remains a powerful method and that testing for carryover effects makes sense only if the null hypothesis of no treatment effect cannot be rejected.

Clinical Trials as Topic↗

PubMedDate not supplied

Comparison of models for average bioequivalence in replicated crossover designs.

Average bioequivalence (ABE) has been the regulatory standard for bioequivalence (BE) since the 1990s. BE studies are commonly two-period crossovers, but may also use replicated designs. The replicated crossover will provide greater power for the ABE assessment. FDA has recommended that ABE analysis of replicated crossovers use a model which includes terms for separate within- and between-subject components for each formulation and which allows for a subject x formulation interaction component. Our simulation study compares the performance of four alternative mixed effects models: the FDA model, a three variance component model proposed by Ekbohm and Melander (EM), a random intercepts and slopes model (RIS) proposed by Patterson and Jones, and a simple model that contains only two variance components. The simple model fails (when not 'true') to provide adequate coverage and it accepts the hypothesis of equivalence too often. FDA and EM models are frequently indistinguishable and often provide the best performance with respect to coverage and probability of concluding BE. The RIS model concludes equivalence too often when both the within- and between-subject variance components differ between formulations. The FDA analysis model is recommended because it provides the most detail regarding components of variability and has a slight advantage over the EM model in confidence interval length.

Cross-Over Studies↗

PubMed1991

The analysis of failure time data in crossover studies.

Clinical trials of new drugs in the treatment of angina pectoris frequently make use of exercise tests to evaluate efficacy. The crossover design is often employed. The methods commonly used to analyse the various exercise times, for example, 'time to pain', are insensitive and potentially biased by the manner in which they deal with the censored nature of the data. Survival analysis can be adapted for use in crossover trials, both in a relatively simple way, and also through the full power of the Cox model. This is considerably more sensitive and not subject to the same bias. This methodology leads to the use of median survival times to illustrate treatment effects and this provides a practical interpretation of clinical relevance. The estimation of median survival times in crossover trials poses some special problems. The methodology is illustrated throughout by means of a specific two-period example in which atenolol was compared with the combination of atenolol and nifedipine. The three-period design is also briefly discussed.

Analysis of Variance↗

PubMed1993

Analysis of case-crossover designs.

The case-crossover design provides a means to study the effects of transient exposures on the risk of acute illness, for example, the effects of drinking alcohol on the immediate risk of a heart attack. Only cases are required by the design, since each case is effectively its own control; what a case was doing at the time of an acute event is compared with what the case would have been doing usually. Maclure has described an approach based on the Mantel-Haenszel method of analysis. It is shown here how the analysis of case-crossover designs can be achieved by a method of maximum likelihood. The method is quite general and, in principle, can be used to analyse the joint effects of many transient exposures. For binary exposures the Mantel-Haenszel approach is an approximate solution to the likelihood equations. In practice, case-crossover designs are limited by the information available on each case's 'usual' behaviour. Extracting such information requires in-depth questioning, but, in principle, it can be obtained. To do so requires careful questionnaire design. The approach is illustrated by analysis of 24 hour alcohol consumption and the risk of myocardial infarction. The problem with this analysis is how to estimate the probability of what a case would 'usually' have been doing from information on drinking frequency.

Adult↗