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[Use of multilevel models in health research].

OBJECTIVE: The aim of this study was to analyze the use of multilevel methodology in health sciences. DESIGN: A literature search was performed in Medline for articles published between 1995 and 2001. Fifteen search words were used, some of which were "multilevel model", "multilevel analysis", "hierarchical linear model", "mixed model", and "random effects model". A total of 1288 abstracts were retrieved. Two hundred twenty-two of the articles on theoretical and/or applied issues related to multilevel methods were examined to determine their current use, the type of model, the number of levels, the units of analysis and the outcome variables related to health sciences. RESULTS: 66.7% of the articles studied was found with the keywords: "multilevel analysis", "multilevel modelling" and "multilevel model". Fifty-six percent of the articles were multilevel applications in different health sciences. However, in 10% of the articles, the main objective was to present and disseminate the methodology in a language comprehensible to non-specialists. CONCLUSIONS: The use of multilevel modelling in health has increased with time and is being applied in different health areas and specialties. However, it is still not considered a commonly used technique.

Biomedical Research↗

Characterization of QTLs for harvest index and source-sink characters in a DH population of rice (Oryza sativa L.).

A DH population containing 81 DH lines from an indica-japonica cross of rice and an RFLP linkage map consisting of 232 markers were used to map quantitative trait loci(QTLs) for harvest index, biomass, grain yield, sink capacity and plant height by a computer program QTLMapper1.0 based on mixed linear models. A total of 21 significant main-effect QTLs and 9 pairs of epistatic loci were detected. Of these, three detected QTLs for grain yield collectively accounted for 42% of the phenotypic variation with a LOD of 7.10. These three grain yield QTLs were corresponded either to QTLs for harvest index or QTLs for biomass in both locations and directions of additive effects, which sheds light on the genetic basis of the formula 'grain yield = biomass x harvest index'. Four detected QTLs for harvest index collectively explained 46% of the total phenotypic variation and four QTLs for biomass jointly accounted for 64% of the trait variation. No coincidence of harvest index QTLs with any biomass QTLs was found, therefore indicating the possibility of pyramiding favorable alleles for both traits through gene recombination so as to obtain a genotype possessing both high harvest index and heavy plant biomass. Five QTLs for plant height were detected that cumulatively explained 64% of the phenotypic variation with a LOD of 11.62. Among these, three with smaller effects respectively co-located with some of the QTLs for biomass, sink capacity and/or grain yield, but not with any of harvest index QTLs, thus suggesting that plant height was to some extent directly associated with 'source' and 'sink' but not with 'transportation' of the 'source-transportation-sink' concept, at least in this genetic background and environment. In view of a somewhat low resolution of the genetic map used in the study and the fact that when plant height QTLs co-located with those for yield and/or yield related traits, these co-located QTLs were all in the same directions of additive effects, it is more likely that these QTLs co-located in a same chromosomal region might be a single QTL which have effects on multiple traits. If this is true, the above observation have led us to assume that QTLs which have pleotropic effects on yield and/or yield related traits and plant height are very different from those which had relatively large effects only on plant height. The former contribute strongly to yield and/or yield related traits but weakly to plant height while the later contribute mainly to plant height. Obviously, due to that an increase of plant height is always coupled with an increase in lodging susceptibility, discriminating between above two types of QTLs is critical in breaking the traits' undesired association in breeding for improved yield potential of rice. In addition, based on the co-location analysis of main-effect QTLs for the studied traits, five genomic regions were found to be highly associated with harvest index, biomass, sink capacity and grain yield.

Biomass↗

Community- and individual-level determinants of Wuchereria bancrofti infection in Leogane Commune, Haiti.

We conducted a school-based assessment of the geographic distribution of Wuchereria bancrofti infection in Leogane Commune, Haiti, using the immunochromatographic test. In multivariate analyses performed using generalized linear mixed models, children attending schools in the foothills and plains were 3.95 (95% confidence interval [CI] = 1.28-12.23) and 23.56 (95% CI = 8.99-61.79) times as likely to be infected, respectively, as children attending mountain schools. Infection prevalence decreased with increasing altitude, but some local foci of infection were detected at higher altitudes. Higher school tuition, a marker of socioeconomic status (SES), was not associated with decreased infection prevalence. Our results indicate that although the force of infection in Leogane Commune is greatest below 70 meters above sea level, higher altitude communities are not exempt from infection. Lymphatic filariasis (LF) elimination programs should consider extending infection mapping activities to presumed non-LF altitudes. In addition, higher SES does not confer protection against W. bancrofti infection.

Animals↗

Bulk tank milk urea nitrogen: seasonal patterns and relationship to individual cow milk urea nitrogen values.

The objectives of this study were: 1) to determine if bulk tank milk urea nitrogen (BTMUN) and whole herd weighted average of the individual cow MUN levels (WHMUN) were equivalent measurements of herd MUN status; and 2) to determine the seasonal variation in BTMUN concentrations in Prince Edward Island (PEI) dairy herds. For BTMUN-WHMUN correlation testing, bulk tank milk samples from 176 herds were tested for MUN once every 1 to 2 wk between September 1999 and August 2002, as part of routine BTM testing for milk components. During this 3-year period, all herds had all milking cows tested for MUN once a month at the same lab. The WHMUN levels (weighted for milk production) were calculated for each month, and were compared to BTMUN levels using a concordance correlation coefficient (CCC) and a graphic procedure. Tests were only compared if they occurred on the same date, producing a final dataset of 669 comparisons. The BTMUN had good (but not perfect) correlation with WHMUN (CCC = 0.91). This high reliability extended to both the pasture and non-pasture seasons, various milk sampling protocols, and all herd sizes seen in PEI. For evaluating the seasonal variation of BTMUN, the 3 y worth of data (24 803 observations) were divided into 15 seasonal categories, 5 seasons per year (early, mid, and late pasture, and early and late stable). Using linear mixed modelling, significantly (P < 0.05) higher BTMUN values were found during the mid and late pasture seasons of 2000, likely because the precipitation was unusually high during this period, enhancing pasture growth.

Animals↗

Characterization of the genetic basis for yield and its component traits of rice revealed by doubled haploid population.

Main-effect QTL, epistatic effects and their interactions with environment are important genetic components of quantitative traits. In this study, we analyzed the QTLs, epistatic effects and QTL by environment interactions (QE) underlying nine traits of yield and yield-component, using a doubled-haploid (DH) population consisted of 190 lines from the cross between an indica parent Zhenshan 97 and a japonica parent WYJ 2, and tested in two-year replicated field trials. A genetic linkage map with 179 SSR (simple sequence repeat) marker loci was constructed. A mixed linear model approach was applied to detect QTLs, digenic interactions and QEs for the nine traits. In total, 57 QTLs of main effects, 41 digenic interactions, eight QEs and seven interactions of epistasis by environment were detected. Each of the main-effect QTLs individually explained 1.3 % to 25.8% of the phenotypic variations. And they collectively explained 11.5% to 66.8% of the phenotypic variations for these traits. Most of the traits (except seed setting) had the QTLs simultaneously detected in two years. Many of the traits shared same QTLs with each other, which is consistent with their significant phenotypic correlations. The pleiotropism or tight linkage of QTLs for different traits might be the important genetic base for trait correlations. The environmental influences on the stability of the trait performance were also discussed.

Crops, Agricultural↗

Circulating endogenous retinoic acid concentrations among participants enrolled in a randomized placebo-controlled clinical trial of retinyl palmitate.

Retinoids have been studied extensively for their chemopreventive properties. The biological activity of retinoids is acquired through their conversion to retinoic acid (RA). Characterization of endogenous circulating RA concentrations after supplementation with vitamin A over longer time periods has not been done previously. Our investigation was conducted to determine whether vitamin A (retinyl palmitate) supplementation significantly increases circulating RA concentrations of all-trans-, 9-cis-, and 13-cis-RA. Using plasma samples from 41 participants enrolled in a randomized clinical trial of placebo, 25,000, 50,000, or 75,000 IU supplemental retinyl palmitate daily, high-performance liquid chromatography analyses were conducted for concentrations of three RA isomers. Seven plasma samples were analyzed for each participant over a 16-month period. Based on an intention-to-treat analysis, results obtained using linear mixed models showed that supplementation with retinyl palmitate statistically significantly increased concentrations of all three RA isomers from baseline levels. This study suggests that supplementation with retinyl palmitate is an effective means to increase circulating all-trans, 9-cis-, and 13-cis-RA concentrations among humans.

Aged↗

The effect of adhesive and flowable composite on postoperative sensitivity: 2-week results.

OBJECTIVE: To measure 2-week postoperative sensitivity in Class II composite restorations placed with a self-etching adhesive (Clearfil SE Bond) or a total-etch adhesive (Prime&Bond NT) with or without a flowable composite as cervical increment. METHOD AND MATERIALS: Upon approval by the University of Guarulhos Committee on Human Subjects, 100 restorations were inserted in 46 patients who required Class II restorations in their molars and premolars. Enamel and dentin walls were conditioned with a self-etching primer (for Clearfil SE Bond) or etched with 34% phosphoric acid (for Prime&Bond NT). A 1- to 2-mm-thick increment of a flowable composite (Filtek Flow) was used in the proximal box in 50% of the restorations of each adhesive. Preparations were restored with a packable composite (Surefil). The restorations were evaluated preoperatively and 2 weeks postoperatively for sensitivity to cold, air, and masticatory forces using a visual analog scale. Marginal integrity of the accessible margins was also evaluated. Statistical analysis used a mixed linear model with subject as a random effect. RESULTS: Ninety-eight teeth from 44 subjects were observed at 2 weeks. The type of adhesive and use of flowable composite had no significant effects or interaction for any of the four outcomes of interest, ie, change from baseline to 2 weeks in sensitivity and response time for the cold or air stimulus. For the air stimulus, the overall average change from baseline was not significant for either sensitivity or response time. For the cold stimulus, the overall average change from baseline was significant for both sensitivity and response time. No case of sensitivity to masticatory forces was observed. CONCLUSION: No differences in postoperative sensitivity were observed between a self-etch adhesive and a total-etch adhesive at 2 weeks. The use of flowable composite did not decrease postoperative sensitivity.

Acid Etching, Dental↗

Health conditions of growing-finishing pigs in fully-slatted pens and multi-surface systems.

The health status of finishing pigs was investigated in 97 farms with either fully-slatted pens (SF, n = 39) or littered multi-surface systems with outdoor yard (MS, n = 58). Pigs (11,194) were checked twice by one person at the beginning and the end of the fattening period in summer or winter. Animal health was determined by the presence of skin and tail lesions, lameness, coughing and sneezing. Housing and management practices were recorded by answering a detailed questionnaire. After merging health information with the questionnaire the data were analysed using generalised mixed linear models. Prevalence rates of health disorders were low (tail = 0.9%; skin = 2.6%; lameness = 0.6 %, coughing = 2.2 %; sneezing = 9.5 %). Pigs exposed to MS showed a lower odds ratio (OR) for tail (OR = 0.22; p < 0.0001) and skin lesions (OR = 0.29; p = 0.002) compared to pigs on SF (OR = 1.0). Conversely, pigs kept in MS had a 3.0 times higher risk of lameness than pigs on SF. No significant housing effects were found for any of the respiratory disorders. Health disorders were strongly affected by the random herd effect (p < 0.0001) indicating the impact of farm layout, management practices and motivational aspects for the animal health status at farm level.

Animal Husbandry↗

Oral protein-energy supplements in peritoneal dialysis: a multicenter study.

BACKGROUND: Protein-energy malnutrition is prevalent in peritoneal dialysis (PD) patients and is associated with increased morbidity and mortality. OBJECTIVE: To evaluate the impact of prophylactic treatment with an oral protein-energy supplement (Protenplus; Fresenius AG, Bad Homburg, Germany) on nutritional parameters in patients starting PD. DESIGN: Prospective, multicenter, randomized study of group A patients (Protenplus, n = 35) and group B (controls, n = 30), with evaluations at baseline and at 6 and 12 months. STATISTICAL METHODS: Efficacy of factors by linear mixed model analysis for repeated measurements, chi-square, t-test, and Mann-Whitney test. OUTCOME PARAMETERS: Patient compliance, serum albumin, and other nutritional parameters. RESULTS: No significant differences were found at baseline evaluation. During follow-up, a significant number of group A patients abandoned intake of the supplement due to non-compliance (n = 7) or side effects (n = 8) (chi2 p < 0.01). Patients with lower residual renal function were less likely to comply. The mixed model in the "intention to treat" analysis showed a significant increase related to supplement intake only in total lymphocyte count in group A. The "as treated" analysis of the 29 patients who fulfilled the study (9 in group A, 20 in group B) disclosed that belonging to group A constituted an independent factor for increased lymphocyte count (p < 0.001), body weight (p < 0.03), tricipital skinfold thickness (p < 0.01), middle-arm muscle circumference (p < 0.025), lean body mass (LBM) (p < 0.002), creatinine LBM related to body surface area (p < 0.001), and creatinine generation rate (p < 0.002). However, these data may have been biased by the high rate of noncompliance in group A. CONCLUSIONS: Protenplus proved to be unsuitable as a long term, oral protein-energy supplement in PD patients due to a high rate of noncompliance and intolerance, primarily among patients with lower residual renal function. The question of whether other products, better-tolerated as nutritional supplements, could compensate for daily protein peritoneal losses in long-term PD remains open.

Adolescent↗

Heterogeneity of daily pulmonary function in response to air pollution among asthmatic children.

Several epidemiological studies have demonstrated the association of short-term exposure to air pollution with transient declines in pulmonary function. Although the magnitudes of declines in pulmonary function found in these studies are relatively small, the effects vary among children. This study examined whether the variation is evidence of biological heterogeneity or due to random variation by analyzing data from a panel study of 83 asthmatic school children exposed to SO2 and PM10 in the Mae Moh district of Thailand. Daily pulmonary function testing was performed on the children for 61 days. General linear mixed models were used to examine and test for the null hypothesis of no variation in the subject-specific slopes of pulmonary functions in response to the air pollutants. The individual daily pulmonary functions measured were FVC, FEV1, PEFR, and FEF(25-75%). These were used as an outcome to compare with air pollutant concentrations as random effects, adjusting for height, gender, time, and temperature. The results indicate evidence of inter-individual variation for subject-specific changes in FVC, FEV1, and PEFR due to the effects of SO2 and PM10 on children. In conclusion, even at low concentrations of daily SO2 and PM10 in the study area, there is evidence of a heterogeneous response to short-term exposure to SO2 and PM10 in children.

Adolescent↗

Multivariable conditional analysis for complex trait and its components.

Methods of multivariable conditional analysis were proposed for analyzing contribution of component traits to complex target trait based on mixed linear model approaches. The contribution ratio and the contributed genetic effect were defined. The contribution ratio could measure the proportion of genetic variation of the given component trait on the target trait. The contributed genetic effect could quantify genetic effect of the given component traits contributed to the target trait. A worked example from the cotton data is given to illustrate the application of the new methods for analyzing the contribution of three yield components to lint yield.

Breeding↗

[Pridiction of the Sex-effects of the Cocoon Quality Characters in Silkworm.].

In this paper , the sex-effects of the cocoon quality characters in silkworm was predicted with Mixed linear model úThe fact that the probability of effect variance and predictability of random gender of whole cocoon weight, cocoon shell weight, ratio of cocoon shell and pupa weight reached a level of extreme significance showed that the gender effect of the four traits was extremely significant, which matched with the reality completely. The predictive values of gender effect of the four traits of female(male) were 0.248g (-0.247g), 2.423cg(-2.394)cg, -1.976%(1.992%) and 0.224g(-0.223g) respectively. Each trait showed single peak distribution after adjusting by sex-effects, which fitted for the request that quantitative traits should show continuously normal standard distribution if QTL analysis was taken.

Animals↗

[QTL mapping and interaction analysis of genotype x environment (Fe2+ -concentrations ) for mesocotyl length in rice (Oryza sativa L.)].

A recombinant inbred lines (RILs) population derived from a cross between Zhenshan97B and Miyang46 was used for detecting QTLs with additive effects and additive-by-additive epistasis for rice mesocotyl length. A linkage map consisting of 207 DNA markers,distributing on the 12 chromosomes of rice,was employed for QTL mapping by using software QTL Mapper 1.6 of mixed linear model. Rice mesocotyl length under germination conditions with 4 different FeSO4 concentrations (0, 1.79, 7.16, 14.32 mmol/L) was measured 7 days after planting. A total of 6 QTLs with significant additive effects on chromosome 1, 5 and 9, with variance explained of 3.5%-11.4%, eleven QTLs with significant additive x additive epistatic effects on chromosome 1, 2, 3, 4, 5, 8 were detected, with variance explained of 4.5%-8.1%. In addition, one QTL for environmental interaction (Fe2+ -concentrations) was detected.

Alleles↗

[Study on the genetic basis of plant height and ear height in maize (Zea mays L.) by QTL dissection].

One hundred and ninety-one F2 individuals derives from the cross, Mo17xHuangzao4, were genotyped by SSR and AFLP markers to construct the genetic linkage map, and 184 corresponding F2:3 families were phenotyped for maize (Zea mays L.) plant hright and ear height in Changping and Shunyi. A mixed linear model approach and its software were used to detect QTLs with main effect, QTLs involved in digenic interations and Q x E interations. In total, 7 QTLs of plant height, 18 pairs of digenic epistatic loci of plant height, 13 pairs of digenic epistatic loci of ear height were detected. It was found that 6 QTLs of plant height, 8 QTLs of ear height, and 4 pairs of digenic epistatic loci of plant height and ear height and a significant interaction with environments. Genetic compnents underlying these quantitative traits were analyzed, and the study showed that additive, dominance and epistaship between plant height and ear height, and the results described above were also discussed for their possible application in molecular breeding.

Breeding↗

Does initial choice of antimicrobial therapy affect length of stay for patients with complicated intra-abdominal infections?

Outcomes for complicated intra-abdominal infection are influenced by operation for source control, patient-related factors, and medical management, including antibiotic treatment. We analyzed length of stay (LOS) at 33 hospitals for 2,150 patients discharged between February 2002 and June 2003, who were > 18 years, had intra-abdominal infection, and received one of 6 first-line antimicrobials. A regression tree analysis selected important variables, their interactions, and their order of significance in explaining LOS. A linear mixed model evaluated the difference in LOS between treatment groups. Adjusted LOS was calculated by the least squares means from the model and was used to assess treatment differences. Mean LOS analyzed by initial antimicrobial therapy and stratified by diagnosis showed LOS for ampicillin/sulbactam and ertapenem to be significantly shorter from levofloxacin, ceftriaxone, and piperacillin/tazobactam (all P < 0.05). Adjusting for all other factors, the variables associated with severity (e.g., diagnosis, ICU stay, and comorbidities) had the greatest impact on adjusted LOS (all P < 0.001). Our findings indicate ampicillin/sulbactam and ertapenem were associated with shorter hospital stays, which may be explained by unaccounted for underlying severity of infection and/or by surgeons stratifying antimicrobial selection according to severity of illness.

Abdominal Cavity↗

Long-term clinical experience with pure bicarbonate peritoneal dialysis solutions.

OBJECTIVES: The aim of this prospective study was to collect long-term experience in incident peritoneal dialysis (PD) patients treated with pure bicarbonate-buffered PD fluids. METHODS: The metabolic parameters acidosis, acid-base status, adequacy, fluid balance, nutritional markers, calcium, phosphorus, parathyroid hormone (PTH), and general laboratory work and medication were compared between incident PD patients in two groups: one treated with a 34 mmol/L bicarbonate-buffered PD fluid (BIC), the other with a 35 mmol/L lactate-buffered PD fluid (LAC). The observation period included 5 visits from 1 month (visit 1) until 12 months (visit 5) after the start of dialysis treatment. For the descriptive analysis, means and standard deviations were calculated. Student's t-test and linear mixed models were used to compare the two treatment groups. RESULTS: 36 patients were followed for 12 months, 18 in the BIC group and 18 in the LAC group. Statistically significant differences between the groups (at the end of study) were found. In BIC group, venous plasma bicarbonate was 27.4 +/- 2.3 mmol/L, base excess 0.8 +/- 2.2 mmol/L, and pH 7.31 +/- 0.05; in LAC group, venous bicarbonate was 25.9 +/- 2.4 mmol/L, base excess -0.6 +/- 2.1 mmol/L, and pH 7.30 +/- 0.04. No patient from the BIC group needed oral bicarbonate, in contrast to 4 patients in the LAC group. Whereas peritoneal urea and creatinine clearances did not differ between the groups, there was better renal solute clearance in the BIC group, accompanied by better-preserved diuresis at 12 months (1333 +/- 935 mL with BIC vs 839 +/- 556 mL with LAC). The reverse was true for ultrafiltration. CONCLUSIONS: Pure bicarbonate-buffered PD solutions were superior in correcting metabolic acidosis and they allowed omission of oral bicarbonate. The minor ultrafiltration with bicarbonate-buffered PD solutions was counterbalanced by better-preserved residual renal function with these solutions.

Acidosis↗

Clinical evaluation of a resin-modified glass-ionomer liner for cervical dentin hypersensitivity treatment.

PURPOSE: To evaluate the effectiveness of two agents for treating cervical dentin sensitivity associated with gingival recession or noncarious cervical lesions. METHODS: 44 patients with at least mild sensitivity affecting cervical dentin were enrolled in a longitudinal randomized clinical trial. A resin-based desensitizer or an experimental glass-ionomer was assigned to treat at most two teeth from each side of the mouth. Sensitivity was assessed by tactile and cold tests, measured with a Visual Analogue Scale at baseline, after treatment, and at 1 week, 1, 3, 6, and 12 months after treatment. Other noteworthy clinical observations were recorded. RESULTS: Both treatments effectively reduced dentin sensitivity (mixed linear model analysis). Sensitivity score for the glass-ionomer was significantly lower than for the resin-based desensitizer after treatment and at all follow-up periods (P < 0.0001). Some overhanging margins were observed in the glass-ionomer group, which could accumulate plaque and cause gingivitis. Despite material loss from some teeth treated with the glass-ionomer, the follow-up sensitivity scores were still lower than baseline scores.

Adult↗

Borderline personality features in childhood: a short-term longitudinal study.

Borderline personality disorder is a particularly devastating, yet understudied form of psychopathology. One of the most significant gaps in existing knowledge is the lack of systematic, prospective empirical attention to the developmental precursors of borderline personality. The present investigation was an exploratory attempt to address this limitation through (a) development of a psychometrically sound self-report instrument that assesses borderline personality features in childhood, the Borderline Personality Features Scale for Children (BPFS-C); (b) examination of the stability of BPF in childhood; (c) evaluation of gender differences in BPF in childhood; and (d) evaluation of the specificity of the BPFS-C for assessing borderline personality features. These goals were achieved through the prospective study of a normative sample of 400 (54% female) fourth though sixth graders who were assessed during the Fall of Year 1, Spring of Year 1, and Fall of Year 2. The use of linear mixed modeling techniques provided evidence for the construct validity of the BPFS-C. Further, borderline personality features as assessed with the BPFS-C were found to be moderately stable over the course of the study, with girls reporting higher levels of BPF than boys. Results also demonstrated that children's scores on the BPFS-C were uniquely related to indicators of borderline personality pathology above and beyond their scores on the Children's Depression Inventory. The implications of these results for the study of the development and etiology of borderline pathology are discussed.

Aggression↗