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PubMed1999

Expression of SET is modulated as a function of cell proliferation.

We explored a biological role of SET as it relates to cell proliferation and differentiation. Immunohistochemical staining demonstrated that the expression of SET was ubiquitous and diffuse over the whole embryo on gestational day 15. At a later stage of development, SET was expressed at relatively lower levels and localized to specific tissues and cells. On embryonic day 19, specific SET immunoreactivity was found in the epithelium of skin, respiratory tract, intestine, and retina as well as in muscle and cartilage. In these cells SET was stained mostly in the nucleus, which was supported indirectly by nuclear transport of enhanced green fluorescence protein-SET fusion proteins in ECV304 endothelial cells. Set mRNA expression was further confirmed in various cultured cells, including NIH 3T3 cells, L6 myoblast cells, human umbilical vein endothelial cells, and ECV304 cells. Using F9 teratocarcinoma cell lines, which were stimulated to differentiate into the two different cell lineages of parietal and visceral endoderm, we have further examined the role of SET. The expression of set mRNA and SET protein was diminished about three-fold in both differentiated endoderm cells compared to the undifferentiated F9 cells. However, when F9 cells were subjected to serum starvation, reduction of set mRNA abundance also took place at a similar level to that observed in response to differentiation. Consistent with this, quiescent L6 myoblast showed a marked downregulation of set mRNA compared to proliferating cells. These results suggest that SET is involved mainly in the regulation of cell proliferation rather than differentiation during embryonic development.

3T3 Cells↗
PubMed1998

Importance of selected athletic trainer employment characteristics in collegiate, sports medicine clinic, and high school settings.

OBJECTIVE: We examined employer importance ratings of 35 employee characteristics in the collegiate, sports medicine clinic, and high school settings and made comparisons among these settings. DESIGN AND SETTING: All prospective employers were sent a survey. Of the 472 surveys mailed, 282 (60%) were returned, with a sample error rate of 1.9%. SUBJECTS: All prospective employers listed on the NATA position vacancy notices from January 1, 1994 to October 1, 1994. MEASUREMENTS: Employers were asked to rate 35 employee characteristics as "not important" " minimally important," " important." or "very important." Additionally, employers chose 1 of 15 job descriptors that best identified their position vacancy. These 15 descriptors were then categorized into collegiate, sports medicine clinic, and high school settings. Discriminant analysis and analysis of variance procedures were used to determine if the 35 employee characteristics differed across the 3 settings. RESULTS: The discriminant analysis produced 2 significant discriminant functions (P < .05) with 23 of the original 35 characteristics remaining in the analysis. The first function discriminated between the collegiate setting and the other settings, with the collegiate setting scoring the highest. The second function discriminated among all 3 groups, with the sports medicine clinic and high school settings scoring the highest and lowest, respectively. Additionally, the analyses of variance (ANOVAs) revealed that 21 of the characteristics remaining in the discriminant analysis differed across the 3 settings. CONCLUSIONS: Employers from all 3 settings rated educational program reputation, written recommendations, job interview performance, and NATA-BOC certification eligibility as important to very important. For the collegiate setting, 7 characteristics were rated above important and included such characteristics as possession of a master's degree and collegiate experience. For the sports medicine clinic, 8 characteristics were rated above important and included sports medicine clinic experience, high school experience, and sport-specific experience. Finally, for the high school setting, 5 characteristics were rated above important. These included NATA-BOC certification, a bachelor's degree, and high school experience.

Journal Article↗
PubMedDate not supplied

[Spatial synchronization of cortical electrical activity at different stages of visual set in preschool children].

Changes in the alpha-rhythm synchronization were revealed at different stages of cognitive visual set in 5- to 7-year-old children. We found a clear-cut correlation of these changes with set plasticity. In children with a plastic set, the EEG synchronization between the frontal and other brain regions substantially increased in the period of set-shifting (the actualization stage). At the set extinction stage, after set-shifting has already taken place, the EEG-synchronization becomes minimal. On the contrary, in children who formed a rigid set, EEG coherence considerably increases at the set extinction stage. This finding suggests that the rigid set still affects the cognitive activity even after (judging from oral reports) the set shift has been completed. The age-related differences in cognitive set formation clearly correlate with the time course of the EEG synchronization between the frontal and other brain regions. We think that the ability to form a plastic visual set depends on the frontal cortex maturation, which occurs at the age of 6-7 years, and its age-related effect on the brain cognitive functions.

Age Factors↗
PubMed1998

Estimating risk associated with care in alternative settings: deterioration among children hospitalized.

BACKGROUND: Although managed care favors use of alternative settings in an attempt to avoid hospitalization, uncertainty about possible deterioration creates concern about their safety. OBJECTIVE: To derive preliminary estimates for the risk of adverse outcome in children hospitalized with acute illness who met criteria for admission to potentially less-expensive, alternative settings (eg, short-stay unit, home nursing). DESIGN: Description of hospitalization outcomes for a community-wide childhood population. SETTING AND POPULATION: All 11591 hospitalizations for residents of Monroe County (Rochester), New York, aged 1 month to 18 years in 1991 and 1992. MEASUREMENTS: To identify potential adverse outcomes in alternative settings (numerator estimate), hospital medical records for admissions to regular inpatient units were examined. To ascertain deterioration among these admissions, detailed record reviews were conducted if the child died or was transferred to another hospital or to a critical care unit. To estimate the total number of admissions eligible for care in alternative settings (denominator estimate), hospital discharge files were analyzed. RESULTS: Deterioration was found in 83 medical admissions. Of these 83, major chronic problems (n=53) or severe illness at presentation (n=27) precluded alternative setting eligibility, leaving only 3 in whom alternative setting care might have been considered. The total number of admissions eligible for alternative setting care was estimated between 1661 (restrictive criteria) and 3322 (inclusive criteria) for the 2-year observation period. Based on these observations, best- and worst-case estimates for the risk of deterioration in candidates for care in alternative settings were 0.6 and 1.8 per 1000, respectively. For the 3 children for whom alternative setting care might have been considered, the shortest period from first indication of deterioration to arrival in the critical care unit was 3.0 hours. CONCLUSIONS: These preliminary estimates suggest that alternative settings may be safe for the care of many children currently hospitalized. A randomized clinical trial to evaluate directly the potential benefits and harms of alternative setting care should be considered.

Adolescent↗
PubMed2004

OMERACT-OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited.

BACKGROUND: The OARSI Standing Committee for Clinical Trials Response Criteria Initiative had developed two sets of responder criteria to present the results of changes after treatment in three symptomatic domains (pain, function, and patient's global assessment) as a single variable for clinical trials (1). For each domain, a response was defined by both a relative and an absolute change, with different cut-offs with regard to the drug, the route of administration and the OA localization. OBJECTIVE: To propose a simplified set of responder criteria with a similar cut-off, whatever the drug, the route or the OA localization. METHODS: Data driven approach: (1) Two databases were considered: the "elaboration" database with which the formal OARSI sets of responder criteria were elaborated, and the "revisit" database. (2) Six different scenarios were evaluated: The two formal OARSI sets of criteria; Four proposed scenarios of simplified sets of criteria. Data from clinical randomized blinded placebo controlled trials were used to evaluate the performances of the two formal scenarios with two different databases ("elaboration" versus "revisit") and those of the four proposed simplified scenarios within the "revisit" database. The placebo effect, active effect, treatment effect, and the required sample arm size to obtain the placebo effect and the active treatment effect observed were the performances evaluated for each of the six scenarios. Experts' opinion approach: Results were discussed among the participants of the OMERACT VI meeting, who voted to select the definite OMERACT-OARSI set of criteria (one of the six evaluated scenarios). RESULTS: Data driven approach: Fourteen trials totaling 1886 OA patients and fifteen studies involving 8164 OA patients were evaluated in the "elaboration"and the "revisit" databases respectively. The variability of the performances observed in the "revisit" database when using the different simplified scenarios was similar to that observed between the two databases ("elaboration" versus "revisit") when using the formal scenarios. The treatment effect and the required sample arm size were similar for each set of criteria. Experts' opinion approach: According to the experts, these two previous performances were the most important of an optimal set of responder criteria. They chose the set of criteria considering both pain and function as evaluation domain and requiring an absolute change and a relative change from baseline to define a response, with similar cut-offs whatever the drug, the route of administration or the OA localization. CONCLUSION: This data driven and experts' opinion approach is the basis for proposing an optimal simplified set of responder criteria for OA clinical trials. Other studies, using other sets of OA patients, are required in order to further validate this proposed OMERACT-OARSI set of criteria.

Clinical Trials as Topic↗
PubMed1996

Which setting of the dynamometer provides maximal grip strength?

The purpose of this study was to determine which setting of the clinical dynamometer produced maximal grip strength and to correlate that setting with characteristics of the individual. Using a computerized isometric dynamometer, the maximal grip strength was determined in 288 normal asymptomatic hands in 4- to 78-year-old individuals at five dynamometer size settings. The majority of hands (256, or 89%) had a maximal grip strength at setting II. Mean body weight and mean height were lower in the group that had a maximal strength at or equal to setting I than in those individuals with maximal setting II and above. However, no clear significant correlation between body mass or hand size and maximal setting was evident. Those with a maximal grip at setting III or IV did not have larger hands or other features that differed from those with maximal settings at II. If measured at setting II only, maximal grip strength would have been underestimated in about 10% of individuals, but the error was small, ranging from 2% to 24%. Since no feature was identified that predicted maximal grip strength setting, it is recommended that grip strength of all patients should be routinely measured at setting II, irrespective of age, weight, or hand dimensions.

Adolescent↗
PubMed1995

The effect of conversational setting on topic continuation in mother-child dyads.

Twelve children (five boys and seven girls, mean age 4; I) interacted with their mothers in two conversational settings: playing with a favourite toy and helping to prepare lunch or muffins. The percentage of two topic continuation processes--topic incorporation and collaboration--used by mothers and children was analysed. It was hypothesized that the help setting with a predetermined structure would elicit a greater percentage of topic incorporation by the dyads than the play setting. In fact, the play setting elicited a greater percentage of topic incorporation from mothers than the help setting. Children did not differ significantly in the percentage of use of topic incorporation between the two settings, but appeared to be equally proficient in incorporating topics in settings with and without a predetermined structure. The play setting also elicited more topic collaboration from the children than the help setting. While the help setting appeared to support collaborative action, the play setting permitted the dyads to be informative about the toys as well as related topics. Therefore, the two settings provided different opportunities for the dyads to continue topics.

Child Language↗
PubMed2002

Intravascular administration sets are accurate and in appropriate condition after 7 days of continuous use: an in vitro study.

BACKGROUND: The ideal duration of intravascular administration set use is unknown. Studies have compared the infective implications of 1--7 days of use. The Centers for Disease Control recommend at least 3 days usage. No previous study has evaluated the accuracy of volume delivery or integrity of administration sets after prolonged use. AIM: To evaluate the accuracy and condition of intravascular administration sets used continuously for 7 days. DESIGN: Prospective, randomized, experimental study in the laboratory setting. METHODS: Four administration sets were randomly assigned to deliver 2 mL/hour (IMEDreg syringe set 2280--0000), 20, 50 or 100 mL/hour (IMEDreg infusion sets 2210--0500) of crystalloid solution continuously for 7 days through an IMEDreg Geminireg four channel infusion pump (PC4). At study commencement and daily for 7 days, a 4-hour volume measurement and an inspection for leaks/erosion of administration sets occurred for each administration set (total measurements = 32). RESULTS: Mean volume outputs over 4 hours were 7.84 mL (2 mL/hour), 80.66 mL (20 mL/hour), 205.35 (50 mL/hour) and 406.37 (100 mL/hour). These differed significantly from the programmed volumes (P=0.00--0.01). Usage duration did not influence performance (F=0.866, P=0.55). Accuracy of volume delivery differed significantly with pump speed (F=106.933, P < 0.001) exhibiting increased volume to 50 mL/hour then a reduction at 100 mL/hour. Differences were within manufacturer specifications (+/-5%) and were clinically acceptable. All administration sets remained in appropriate condition displaying no leakage or erosion. CONCLUSION: There were small inaccuracies found between programmed and delivered volumes, however, there was no deterioration in performance over time. This suggests that inaccuracies were because of normal pump performance rather than the administration sets. Administration sets retain acceptable accuracy and condition after 7 days continuous use. Further research should assess the infective and other impacts of prolonged usage.

Analysis of Variance↗
PubMed1997

Impact of the method of calculation on assessment of the PTH-calcium set point.

BACKGROUND: Although the methodology for calculating the PTH secretory parameters is well established, a consensus on a common methodology for calculation of the set point value has not yet been achieved. This is probably one of the major reasons for the conflicting results obtained for this secretory parameter. The aim of the present study was to analyse the influence of the different methods of calculation on the values of set point obtained in clinical nephrology practice. METHODS: We analysed 68 PTH-calcium sigmoidal curves, obtained by infusion of 37 mg/kg Na2-EDTA i.v. in 2 h and 8 mg/kg Ca gluconate based on the calcium element i.v. in 2 h on two separate days. The set point was calculated according to three different methods: method A, the originally described method, based on the classical four-parameter model, which considers the set point as the calcium concentration corresponding to the PTH value intermediate between the maximal and minimal values (the midrange value method); method B (set point = calcium concentration corresponding to 50% of maximal PTH), and method C (set point = calcium concentration corresponding to 50% inhibition of basal PTH value). The three different sets of set point values were entered into the formula of the sigmoidal curve to test the best fitting of the PTH experimentally observed values. RESULTS: The set point values calculated with the classical midrange value method were lower than the corresponding values calculated by the other two methods; method C gave the highest values. Furthermore the best fitting of the experimentally observed PTH levels was obtained by method A the worst by method C, while method B gave intermediate results. The difference between method A and method B was analysed in order to see if this difference is constant over the whole range of PTH secretory conditions and calcium concentrations. The higher the basal serum calcium concentrations and the lower the suppressibility of PTH, the greater was the overestimation of set point values by method B compared to the midrange value method. CONCLUSIONS: Method A, the midrange value method, gives the set point values closest to the original concept of the four parameter model. Although method B (50% of maximal PTH) is well correlated with the original method, it overestimates the set point values and most importantly, this overestimation is not constant, but largely affected by calcium concentration and by the secretory conditions of parathyroid glands.

Adult↗
PubMed2006

Effects of programming threshold and maplaw settings on acoustic thresholds and speech discrimination with the MED-EL COMBI 40+ cochlear implant.

OBJECTIVES: The principal task in the programming of a cochlear implant (CI) speech processor is the setting of the electrical dynamic range (output) for each electrode, to ensure that a comfortable loudness percept is obtained for a range of input levels. This typically involves separate psychophysical measurement of electrical threshold ([theta] e) and upper tolerance levels using short current bursts generated by the fitting software. Anecdotal clinical experience and some experimental studies suggest that the measurement of [theta]e is relatively unimportant and that the setting of upper tolerance limits is more critical for processor programming. The present study aims to test this hypothesis and examines in detail how acoustic thresholds and speech recognition are affected by setting of the lower limit of the output ("Programming threshold" or "PT") to understand better the influence of this parameter and how it interacts with certain other programming parameters. DESIGN: Test programs (maps) were generated with PT set to artificially high and low values and tested on users of the MED-EL COMBI 40+ CI system. Acoustic thresholds and speech recognition scores (sentence tests) were measured for each of the test maps. Acoustic thresholds were also measured using maps with a range of output compression functions ("maplaws"). In addition, subjective reports were recorded regarding the presence of "background threshold stimulation" which is occasionally reported by CI users if PT is set to relatively high values when using the CIS strategy. RESULTS: Manipulation of PT was found to have very little effect. Setting PT to minimum produced a mean 5 dB (S.D. = 6.25) increase in acoustic thresholds, relative to thresholds with PT set normally, and had no statistically significant effect on speech recognition scores on a sentence test. On the other hand, maplaw setting was found to have a significant effect on acoustic thresholds (raised as maplaw is made more linear), which provides some theoretical explanation as to why PT has little effect when using the default maplaw of c = 500. Subjective reports of background threshold stimulation showed that most users could perceive a relatively loud auditory percept, in the absence of microphone input, when PT was set to double the behaviorally measured electrical thresholds ([theta]e), but that this produced little intrusion when microphone input was present. CONCLUSIONS: The results of these investigations have direct clinical relevance, showing that setting of PT is indeed relatively unimportant in terms of speech discrimination, but that it is worth ensuring that PT is not set excessively high, as this can produce distracting background stimulation. Indeed, it may even be set to minimum values without deleterious effect.

Acoustic Stimulation↗
PubMed1992

Can, a putative oncogene associated with myeloid leukemogenesis, may be activated by fusion of its 3' half to different genes: characterization of the set gene.

The translocation (6;9)(p23;q34) in acute nonlymphocytic leukemia results in the formation of a highly consistent dek-can fusion gene. Translocation breakpoints invariably occur in single introns of dek and can, which were named icb-6 and icb-9, respectively. In a case of acute undifferentiated leukemia, a breakpoint was detected in icb-9 of can, whereas no breakpoint could be detected in dek. Genomic and cDNA cloning showed that instead of dek, a different gene was fused to can, which was named set. set encodes transcripts of 2.0 and 2.7 kb that result from the use of alternative polyadenylation sites. Both transcripts contain the open reading frame for a putative SET protein with a predicted molecular mass of 32 kDa. The set-can fusion gene is transcribed into a 5-kb transcript that contains a single open reading frame predicting a 155-kDa chimeric SET-CAN protein. The SET sequence shows homology with the yeast nucleosome assembly protein NAP-I. The only common sequence motif of SET and DEK proteins is an acidic region. SET has a long acidic tail, of which a large part is present in the predicted SET-CAN fusion protein. The set gene is located on chromosome 9q34, centromeric of c-abl. Since a dek-can fusion gene is present in t(6;9) acute myeloid leukemia and a set-can fusion gene was found in a case of acute undifferentiated leukemia, we assume that can may function as an oncogene activated by fusion of its 3' part to dek, set, or perhaps other genes.

Acute Disease↗
PubMed2005

A motif within SET-domain proteins binds single-stranded nucleic acids and transcribed and supercoiled DNAs and can interfere with assembly of nucleosomes.

The evolutionary conserved SET domain is present in many eukaryotic chromatin-associated proteins, including some members of the trithorax (TrxG) group and the polycomb (PcG) group of epigenetic transcriptional regulators and modifiers of position effect variegation. All SET domains examined exhibited histone lysine methyltransferase activity, implicating these proteins in the generation of epigenetic marks. However, the mode of the initial recruitment of SET proteins to target genes and the way that their association with the genes is maintained after replication are not known. We found that SET-containing proteins of the SET1 and SET2 families contain motifs in the pre-SET region or at the pre-SET-SET and SET-post-SET boundaries which very tightly bind single-stranded DNA (ssDNA) and RNA. These motifs also bind stretches of ssDNA generated by superhelical tension or during the in vitro transcription of duplex DNA. Importantly, such binding withstands nucleosome assembly, interfering with the formation of regular nucleosomal arrays. Two representatives of the SUV39 SET family, SU(VAR)3-9 and G9a, did not bind ssDNA. The trxZ11 homeotic point mutation, which is located within TRX SET and disrupts embryonic development, impairs the ssDNA binding capacity of the protein. We suggest that the motifs described here may be directly involved in the biological function(s) of SET-containing proteins. The binding of single-stranded nucleic acids might play a role in the initial recruitment of the proteins to target genes, in the maintenance of their association after DNA replication, or in sustaining DNA stretches in a single-stranded configuration to allow for continuous transcription.

Amino Acid Motifs↗
PubMed2026

Phylogenetic inconsistency of pairwise SNP clustering for inferring tuberculosis transmission in a high-burden, endemic setting: a case study from Thailand.

Whole-genome sequence analysis is now widely used to delineate tuberculosis transmission clusters. A standard practice is to cluster bacterial isolates based on a fixed maximum genome-wide pairwise single nucleotide polymorphism (pwSNP) distance threshold. In this study, we evaluated the phylogenetic consistency of pwSNP-distance clustering with thresholds ranging between 1 and 25 single nucleotide polymorphisms (SNPs) using two contrasting data sets: (i) a data set from the UK (N = 390) published by T. M. Walker, C. L. C. Ip, R. H. Harrell, J. T. Evans, et al. (Lancet Infect Dis 13:137-146, 2013, https://doi.org/10.1016/S1473-3099(12)70277-3), which was foundational to the establishment of this method, and (ii) a data set from Thailand (N = 3,341), characterized by persistent transmission and sparse, non-systematic sampling. For the UK data set, the standard pwSNP-distance clustering using thresholds of &#x2265;12 SNPs yielded entirely monophyletic clusters and showed high concordance with a comparative monophyly constrained, tree-based method. In contrast, for the Thai data set, pwSNP-distance clustering often generated non-monophyletic clusters, even by the 25-SNP threshold. The pwSNP-distance and comparative tree-based clustering methods only showed large consistency at thresholds of &#x2265;22 SNPs. This suggests that SNP clusters defined by low distance thresholds (i.e., <12 SNPs for the UK data set, and <22 SNPs for the Thai data set) may lack robustness, and the problem is particularly severe for data sets characterized by persistent transmission, likely due to poorer cluster separation. Moreover, our findings indicate that large cluster sizes, high maximum intra-cluster genetic distances, and broad sample collection time spans may serve as useful indicators of potentially non-monophyletic clusters. We also demonstrate that mixed infections can produce spurious, phylogenetically long-range SNP linkages, underscoring the necessity of strict sequence quality control.IMPORTANCEFixed-threshold pairwise single nucleotide polymorphism (pwSNP)-distance clustering is commonly used to delineate tuberculosis transmission clusters. From an epidemiological perspective, a genuine transmission cluster must be monophyletic, originating from a single source. However, pwSNP-distance clustering is inherently simplistic and can therefore violate this principle, making the assessment of its phylogenetic consistency critical. Our results demonstrate that while this method effectively delineated complete transmission clusters for the data set from the UK, a low-burden and non-persistent transmission setting, it frequently generated non-monophyletic clusters when applied to the Thai data set, characterized by persistent transmission alongside sparse and non-systematic sampling. Furthermore, we found that clusters derived using low distance thresholds could notably vary between the pwSNP-distance and comparative tree-based clustering methods, suggesting limited reliability and robustness. To accurately delineate tuberculosis transmission clusters, especially for complex data from high-burden, endemic settings, we recommend transitioning from pwSNP-distance clustering toward more robust, phylogenetic clustering that respects evolutionary descent.

Mycobacterium tuberculosis↗
PubMed2006

Matrix factorization algorithms for the identification of muscle synergies: evaluation on simulated and experimental data sets.

Several recent studies have used matrix factorization algorithms to assess the hypothesis that behaviors might be produced through the combination of a small number of muscle synergies. Although generally agreeing in their basic conclusions, these studies have used a range of different algorithms, making their interpretation and integration difficult. We therefore compared the performance of these different algorithms on both simulated and experimental data sets. We focused on the ability of these algorithms to identify the set of synergies underlying a data set. All data sets consisted of nonnegative values, reflecting the nonnegative data of muscle activation patterns. We found that the performance of principal component analysis (PCA) was generally lower than that of the other algorithms in identifying muscle synergies. Factor analysis (FA) with varimax rotation was better than PCA, and was generally at the same levels as independent component analysis (ICA) and nonnegative matrix factorization (NMF). ICA performed very well on data sets corrupted by constant variance Gaussian noise, but was impaired on data sets with signal-dependent noise and when synergy activation coefficients were correlated. Nonnegative matrix factorization (NMF) performed similarly to ICA and FA on data sets with signal-dependent noise and was generally robust across data sets. The best algorithms were ICA applied to the subspace defined by PCA (ICAPCA) and a version of probabilistic ICA with nonnegativity constraints (pICA). We also evaluated some commonly used criteria to identify the number of synergies underlying a data set, finding that only likelihood ratios based on factor analysis identified the correct number of synergies for data sets with signal-dependent noise in some cases. We then proposed an ad hoc procedure, finding that it was able to identify the correct number in a larger number of cases. Finally, we applied these methods to an experimentally obtained data set. The best performing algorithms (FA, ICA, NMF, ICAPCA, pICA) identified synergies very similar to one another. Based on these results, we discuss guidelines for using factorization algorithms to analyze muscle activation patterns. More generally, the ability of several algorithms to identify the correct muscle synergies and activation coefficients in simulated data, combined with their consistency when applied to physiological data sets, suggests that the muscle synergies found by a particular algorithm are not an artifact of that algorithm, but reflect basic aspects of the organization of muscle activation patterns underlying behaviors.

Algorithms↗
PubMed2005

PAGE: parametric analysis of gene set enrichment.

BACKGROUND: Gene set enrichment analysis (GSEA) is a microarray data analysis method that uses predefined gene sets and ranks of genes to identify significant biological changes in microarray data sets. GSEA is especially useful when gene expression changes in a given microarray data set is minimal or moderate. RESULTS: We developed a modified gene set enrichment analysis method based on a parametric statistical analysis model. Compared with GSEA, the parametric analysis of gene set enrichment (PAGE) detected a larger number of significantly altered gene sets and their p-values were lower than the corresponding p-values calculated by GSEA. Because PAGE uses normal distribution for statistical inference, it requires less computation than GSEA, which needs repeated computation of the permutated data set. PAGE was able to detect significantly changed gene sets from microarray data irrespective of different Affymetrix probe level analysis methods or different microarray platforms. Comparison of two aged muscle microarray data sets at gene set level using PAGE revealed common biological themes better than comparison at individual gene level. CONCLUSION: PAGE was statistically more sensitive and required much less computational effort than GSEA, it could identify significantly changed biological themes from microarray data irrespective of analysis methods or microarray platforms, and it was useful in comparison of multiple microarray data sets. We offer PAGE as a useful microarray analysis method.

Computational Biology↗
PubMed2000

The appropriate setting of noninvasive pressure support ventilation in stable COPD patients.

STUDY OBJECTIVE: To evaluate the short-term physiologic effects of two settings of nasal pressure-support ventilation (NPSV) in stable COPD patients with chronic hypercapnia. DESIGN: Randomized controlled physiologic study. SETTING: Lung function units and outpatient clinic of two affiliated pulmonary rehabilitation centers. PATIENTS: Twenty-three patients receiving domiciliary nocturnal NPSV for a mean (+/- SD) duration of 31 +/- 20 months. METHODS: Evaluation of arterial blood gases, breathing pattern, respiratory muscles, and dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn) during both unassisted and assisted ventilation. Two settings of NPSV were randomly applied for 30 min each: (1) usual setting (U), the setting of NPSV actually used by the individual patient at home; and (2) physiologic setting (PHY), the level of inspiratory pressure support (IPS) and external positive end-expiratory pressure (PEEPe) tailored to patient according to invasive evaluation of respiratory muscular function and mechanics. RESULTS: All patients tolerated NPSV well throughout the procedure. Mean U was IPS, 16 +/- 3 cm H(2)O and PEEPe, 3.6 +/- 1.4 cm H(2)O; mean PHY was IPS, 15 +/- 3 cm H(2)O and PEEPe, 3.1 +/- 1.6 cm H(2)O. NPSV was able to significantly (p < 0.01) improve arterial blood gases independent of the setting applied. When compared with spontaneous breathing, both settings induced a significant increase in minute ventilation (p < 0.01). Both settings were able to reduce the diaphragmatic pressure-time product, but the reduction was significantly greater with PHY (by 64%; p < 0.01) than with U (56%; p < 0.05). Eleven of 23 patients (48%) with U and 7 of 23 patients (30%) with PHY showed ineffective efforts (IE); the prevalence of IE (20 +/- 39% vs 6 +/- 11% of their respiratory rate with U and PHY, respectively) was statistically different (p < 0.05). CONCLUSION: In COPD patients with chronic hypercapnia, NPSV is effective in improving arterial blood gases and in unloading inspiratory muscles independent of whether it is set on the basis of patient comfort and improvement in arterial blood gases or tailored to a patient's respiratory muscle effort and mechanics. However, setting of inspiratory assistance and PEEPe by the invasive evaluation of lung mechanics and respiratory muscle function may result in reduction in ineffective inspiratory efforts. These short-term results must be confirmed in the long-term clinical setting.

Aged↗
PubMed2004

Quantitative analysis of single- vs. multiple-set programs in resistance training.

The purpose of this study was to examine the existing research on single-set vs. multiple-set resistance training programs. Using the meta-analytic approach, we included studies that met the following criteria in our analysis: (a) at least 6 subjects per group; (b) subject groups consisting of single-set vs. multiple-set resistance training programs; (c) pretest and posttest strength measures; (d) training programs of 6 weeks or more; (e) apparently "healthy" individuals free from orthopedic limitations; and (f) published studies in English-language journals only. Sixteen studies generated 103 effect sizes (ESs) based on a total of 621 subjects, ranging in age from 15-71 years. Across all designs, intervention strategies, and categories, the pretest to posttest ES in muscular strength was (chi = 1.4 +/- 1.4; 95% confidence interval, 0.41-3.8; p < 0.001). The results of 2 x 2 analysis of variance revealed simple main effects for age, training status (trained vs. untrained), and research design (p < 0.001). No significant main effects were found for sex, program duration, and set end point. Significant interactions were found for training status and program duration (6-16 weeks vs. 17-40 weeks) and number of sets performed (single vs. multiple). The data indicated that trained individuals performing multiple sets generated significantly greater increases in strength (p < 0.001). For programs with an extended duration, multiple sets were superior to single sets (p < 0.05). This quantitative review indicates that single-set programs for an initial short training period in untrained individuals result in similar strength gains as multiple-set programs. However, as progression occurs and higher gains are desired, multiple-set programs are more effective.

Adolescent↗
PubMed2006

The acute effects of a single set of contrast preloading on a loaded countermovement jump training session.

The aim of this research was to assess the effect of a single set of contrast preloading on peak vertical displacement (PD) during a loaded countermovement jump (LCMJ) training session. Nine strength-trained males participated in 2 randomly assigned, crossover design testing sessions consisting of 5 sets of 6 repetitions of 20-kg LCMJs with 3-minute rest intervals between sets. The preloading intervention was performed 3 minutes after the first set and 4 minutes before the second set of 20-kg LCMJs. The control (CON) group performed 1 set of 20-kg LCMJs, whereas the jump squat (JS) group performed 1 set of 40-kg LCMJs. The number of repetitions performed during each preloading condition was varied to match total concentric work between the 2 sessions. A significant (p < 0.05) preload x set interaction for PD was observed, with the JS group jumping significantly higher during the third set performed after the preload in comparison with the CON group. Analysis of peak power output and mean power output during the concentric movement for this set revealed that as the knee flexion angle increased, the effect of the preload was augmented. These results suggest that a single set of preloading exercises enhances performance during a lower-body explosive power training session; however, the effects of a single preloading set may not peak until midway through the training session.

Adolescent↗