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In the present study, 148 commercial barley cultivars were assessed by 14 AFLP primer combinations and 32 SSRs primer pairs. Population structure, linkage disequilibrium, and genomic regions associated with physiological traits under drought stress were investigated. The phenotypic results showed a high level of diversity between studied cultivars. The studied barley cultivars were divided into two subgroups. Linkage disequilibrium analysis revealed that r 2 values among all possible marker pairs have an average value of 0.0178. The mixed linear model procedure showed that totally, 207 loci had a significant association with investigated traits. 120 QTLs out of 207 were detected for traits under normal conditions, and 90 QTLs were detected for traits under drought stress conditions. Identified QTLs after validation and transferring to SCAR markers in the case of AFLPs can be used to develop MAS strategies for barley breeding programs. Some common markers were identified for a particular trait or some traits across normal and drought stress conditions. These markers show low interaction with environmental conditions (stable markers); therefore, selection by them for a trait under normal conditions will improve the trait value under stress conditions, too., In the present study, 148 commercial barley cultivars were assessed by 14 AFLP primer combinations and 32 SSRs primer pairs as well as 14 Physiological traits under water deficit conditions. Mixed linear model procedure showed that totally, 207 loci had significant association with investigated traits. Some common markers were identified for a particular trait or some traits across normal and drought stress conditions.These markers show low interaction with environmental conditions (stable markers); therefore, selection by them for a trait under normal conditions will improve the trait value under stress conditions, too.

Background Amniotic membrane extract enhances the rate of epithelialisation after corneal ulceration in several species but has not been studied in the equine cornea. Objectives To evaluate the effect of amniotic membrane extract on re-epithelialisation of equine corneal ulcers compared to ulcers treated with antibiotic, antifungal, and mydriatic medical therapy alone; to evaluate equine corneal healing after experimentally induced superficial ulceration. Study design Masked, randomised, controlled experimental trial. Methods Superficial, 8 mm corneal ulcers were created bilaterally in each horse. One eye was treated with amniotic membrane extract; the opposite was control. Both eyes were treated with medical therapy. Treatment eyes received amniotic membrane extract, and control eyes received the amniotic membrane extract vehicle. Ulcers were stained with fluorescein and photographed in 12-hour increments until completely healed. Ulcer surface area was determined by analysing photographs with ImageJ. A mixed linear model was used to compare ulcer surface area and hours until healing between treatment groups. A regression model was also used to calculate corneal re-epithelialisation rate over time. Results Regardless of therapy, healing occurred in two phases: an initial rapid phase of 0.88 mm2 /hr (95% CI: 0.81 - 0.94 mm2 /hr) for approximately 48-54 hours followed by a second, slow phase of 0.07 mm2 /hr (95% CI: 0.04 - 0.09 mm2 /hr). Most eyes healed within 135.5 ± 48.5 hours. Treatment (amniotic membrane extract vs. control) was not significantly associated with size of ulcers over time (P=0.984). Discomfort was minimal to absent in all horses. Main limitations Results achieved experimental studies may differ from outcomes in the clinical setting. Conclusions There was no significant difference in healing rate with addition of amniotic membrane extract to medical therapy for equine superficial corneal ulcers. A biphasic corneal healing process was observed, with an initial rapid phase followed by a slow phase. Further study will be needed to determine if amniotic membrane extract will be helpful for infected or malacic equine corneal ulcers.

Aim To investigate the efficacy of a combination of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) versus an optimized degludec-based multiple daily injections (MDI) regimen + self-monitoring of blood glucose (SMBG) in people with type 1 diabetes with regard to optimizing glucose control. Material and methods The trial included 28 individuals who underwent a 4-week run-in phase, and were then randomized 1:1 to: (a) CSII + CGM followed by MDI + SMBG or (b) an MDI basal-bolus regimen followed by CSII + CGM. Results In patients randomized to the CSII + CGM → MDI + SMBG arm, a significant reduction in glycated haemoglobin (HbA1c) versus baseline was found at the end of the first phase (CSII + CGM) without significant variation in the following MDI + SMBG phase. In the arm randomized to the MDI + SMBG → CSII + CGM sequence, a significant improvement in HbA1c was observed in the first phase (MDI + SMBG), together with a further decrease in the following CSII + CGM phase. In the comparison of the two treatments using a mixed linear model, CSII + CGM was superior to MDI + SMBG with respect to change in HbA1c (P = 0.001). Conclusions This study suggests that CSII + CGM improves glycaemic control without relevant safety issues in type 1 diabetes, in comparison with MDI + SMBG.

BACKGROUND Communication practices used by veterinarians can impact client's involvement in decision-making. The objective of this study was to evaluate the level of client involvement in veterinary care decisions and factors impacting client involvement. METHODS A random sample of practising companion animal veterinarians and a convenience sample of pet owners were recruited. Each consultation was audio-video recorded and analyzed using the Observer OPTION5 instrument, adapted from human medicine, to assess veterinarians' level of shared decision-making. A mixed linear model was used to assess statistical associations between veterinarian, client and appointment-level factors and OPTION5 scores. RESULTS Sixty veterinarians and 909 of their clients were audio-video recorded during a consultation, of which 717 interactions included a decision identified for analysis using the OPTION5 instrument. Elements consistent with shared decision-making were uncommon, with a mean OPTION5 score of 22.6 (median = 20.0; sd = 13.05; range = 0-75) out of 100. OPTION5 scores were positively associated with the length of the appointment and negatively associated with the veterinarian's years in practice when controlling for statistical interaction between client income and appointment type. CONCLUSION Findings suggest an opportunity exists for veterinarians to incorporate more client involvement through increased use of shared decisionmaking behaviours during veterinary consultations.

The plasma very low-density lipoprotein (VLDL) concentration is an effective blood biochemical indicator that could be used to select lean chicken lines. In the current study, we used Genome-wide association study (GWAS) method to detect SNPs with significant effects on plasma VLDL concentration. As a result, 38 SNPs significantly associated with plasma VLDL concentration were identified using at least one of the three mixed linear model (MLM) packages, including GRAMMAR, EMMAX and GEMMA. Nearly, all these SNPs with significant effects on plasma VLDL concentration (except Gga_rs16160897) have significantly different allele frequencies between lean and fat lines. The 1-Mb regions surrounding these 38 SNPs were extracted, and twelve important regions were obtained after combining the overlaps. A total of 122 genes in these twelve important regions were detected. Among these genes, LRRK2, ABCD2, TLR4, E2F1, SUGP1, NCAN, KLF2 and RAB8A were identified as important genes for plasma VLDL concentration based on their basic functions. The results of this study may supply useful information to select lean chicken lines.

BACKGROUND Trust is a core aspect of the patient-physician relationship, especially in cancer care. We sought to examine parents' experiences with trust over the first year after a child's cancer diagnosis. PROCEDURE We conducted a prospective, questionnaire-based longitudinal cohort study of parents and physicians of children with cancer at two academic pediatric hospitals. We evaluated trust among 166 parents of children with cancer over the first year after diagnosis. Surveys were administered after diagnosis, at 4 months, and at 12 months after diagnosis. RESULTS Seventy-one percent of parents trusted the child's oncologist "completely" at baseline, as did 79% at 4 months and 77% at 12 months. At baseline, high-quality physician communication (OR 4.11 [1.78-9.51], P = .001) and information (OR 2.82 [1.29-6.16], P = .01) were associated with trust, after adjustment for parent gender, race/ethnicity, and education. Parents were less likely to trust the physician completely at 12 months if the child had experienced cancer relapse or progression (OR 0.28 [0.10-0.81], P = .02). In a mixed linear model adjusted for parent gender, race/ethnicity, education, and clustering by physician, trust was associated with high-quality communication (OR 3.40 [1.61-7.20], P = .001) and receipt of high-quality information (OR 2.48 [1.18-5.21], P = .02), and inversely associated with relapse or progression (OR 0.39 [0.17-0.92], P = 0.03); trust increased over time (P

Additive effects (A) and additive-by-environment interactions (A×E) for five rice yield components were analysed using 20 SSSLs under mixed linear model methodology. Thirty-one QTLs were detected. Different yield components have different QTL-by-environment (Q×E) interaction patterns. No A×E interaction effects were detected for the four QTLs for panicle number (PN). Four QTLs detected for spikelets per panicle (SPP) had A×E interactions. Five of seven QTLs detected for grains per panicle (GPP), two of 10 QTLs detected for 1000-grains weight (GWT) and three of six QTLs detected for seed set ratio (SSR) showed significant A×E interaction. Most of these QTLs were distributed in clusters across the genome. The complexity of linkage and pleiotropy of these QTLs plus environmental effect may result in the diversity of the yield phenotype in the SSSLs. Only S19 exhibited a significant increase in yield with a predicted gain by 281.58 kg ha−1. The results may be useful to design a better breeding strategy that takes advantage of QTL-by-environment interaction effects in each of the SSSLs.

Objective The aim of this study was to analyze failure modes and misfit of abutments with reduced diameter for both cement and screw retentions after cyclic loading. Material and methods Forty morse-taper abutment/implant sets of titanium were divided into four groups (N = 10): G4.8S-4.8 abutment with screw-retained crown; G4.8C-4.8 abutment with cemented crown; G3.8S-3.8 abutment with screw-retained crown; and G3.8C-3.8 abutment with cemented crown. Copings were waxed on castable cylinders and cast by oxygen gas flame and injected by centrifugation. After, esthetic veneering ceramic was pressed on these copings for obtaining metalloceramic crowns of upper canine. Cemented crowns were cemented on abutments with provisional cement (Temp Bond NE), and screw-retained crowns were tightened to their abutments with torque recommended by manufacturer (10 N cm). The misfit was measured using a stereomicroscope in a 10× magnification before and after cyclic loading (300,000 cycles). Tests were visually monitored, and failures (decementation, screw loosening and fractures) were registered. Misfit was analyzed by mixed linear model while failure modes by chi-square test (α = 0.05). Results Cyclic loading affected misfit of 3.8C (P ≤ 0.0001), 3.8S (P = 0.0055) and 4.8C (P = 0.0318), but not of 4.8S (P = 0.1243). No differences were noted between 3.8S with 4.8S before (P = 0.1550) and after (P = 0.9861) cyclic loading, but 3.8C was different from 4.8C only after (P = 0.0015) loading. Comparing different types of retentions at the same diameter abutment, significant difference was noted before and after cyclic loading for 3.8 and 4.8 abutments. Analyzing failure modes, retrievable failures were present at 3.8S and 3.8C groups, while irretrievable were only present at 3.8S. Conclusions The cyclic loading decreased misfit of cemented and screw-retained crowns on reduced diameter abutments, and misfit of cemented crowns is greater than screw-retained ones. Abutments of reduced diameter failed more than conventional.

Background and purpose Although the genetic contribution to stroke risk is well known, it remains unclear if young-onset stroke has a stronger genetic contribution than old-onset stroke. This study aims to compare the heritability of ischaemic stroke risk between young and old, using common genetic variants from whole-genome array data in population-based samples. Methods This analysis included 4050 ischaemic stroke cases and 5765 controls from six study populations of European ancestry; 47% of cases were young-onset stroke (age

Compliance (C) and resistance (R) maintain a unique, inverse relationship in the pulmonary circulation, resulting in a constant characteristic time [Formula: see text] that has been observed in healthy subjects as well as patients with pulmonary arterial hypertension (PAH). However, little is known about the dependence of right ventricular (RV) function on the coupled changes in R and C in the context of this inverse relationship. We hypothesized three simple dependencies of RV ejection fraction (RVEF) on R and C. The first model (linear-R) assumes a linear RVEF-R relation; the second (linear-C) assumes a linear RVEF-C relation; and the third one combines the former two in a mixed linear model. We found that the linear-R model and the mixed linear model are in good agreement with clinical evidence. A conclusive validation of these models will require more clinical data. Longitudinal data in particular are needed to identify the time course of ventricular-vascular impairment in PAH. Simple models like the ones we present here, once validated, will advance our understanding of the mechanisms of RV failure, which could improve strategies to manage RV dysfunction in PAH.

The aim of this article is to develop methodology for detecting influential observations in crossover models with random individual effects. Various case-weighted perturbations are performed. We obtain the influence of the perturbations on each parameter estimator and on their dispersion matrices. The obtained results exhibit the possibility to obtain closed-form expressions of the influence using the residuals in mixed linear models. Some graphical tools are also presented.

Area level models, such as the Fay–Herriot model, aim to improve direct survey estimates for small areas by borrowing strength from related covariates and from direct estimates across all areas. In their multivariate form, where related population characteristics are jointly modelled, area level models allow for inference about functions of two or more characteristics and may exploit dependence between the response variables to improve small area predictions. When model covariates are observed with random error, such as those drawn from another survey, it is important to account for this error in the modelling. We present a Bayesian analysis of a multivariate Fay–Herriot model with functional measurement error, allowing for both joint modelling of related characteristics and accounting for random observation error in some of the covariates. We apply it to modelling 2010 and 2011 poverty rates of school-aged children for US counties, for predicting 2011 poverty rates and the 2010–2011 changes. For this application, the measurement error model results in great improvements in prediction when compared with the direct estimates, and ignoring the measurement error results in uncertainty estimates that are misleading. We propose a computational approach to implementing this model via an independence chain Markov chain Monte Carlo algorithm and prove the propriety of the posterior distribution under a class of non-informative priors.

Purpose: To investigate the within and between subject variability of quantitative cerebral blood flow (CBF) measurements in normal subjects using various MRI techniques and positron emission tomography (PET). Materials and Methods: Repeated CBF measurements were performed in 17 healthy, young subjects using three different MRI techniques: arterial spin labeling (ASL), dynamic contrast enhanced T1 weighted perfusion MRI (DCE) and phase contrast mapping (PCM). All MRI measurements were performed within the same session. In 10 of the subjects repeated CBF measurements by 15O labeled water PET had recently been performed. A mixed linear model was used to estimate between subject (CVbetw) and within subject (CVwith) coefficients of variation. Results: Mean global CBF, CVbetw and CVwith using each of the four methods were for PCM 65.2 mL/100 g/min, 17.4% and 7.4%, for ASL 37.1 mL/100 g/min, 16.2% and 4.8%, for DCE 43.0 mL/100 g/min, 20.0%, 15.1% and for PET 41.9 mL/100 g/min, 16.5% and 11.9%, respectively. Only for DCE and PCM a significant positive correlation between measurements was demonstrated. Conclusion: These findings confirm large between subject variability in CBF measurements, but suggest also that in healthy subjects a subject-method interaction is a possible source of between subject variability and of method differences. J. Magn. Reson. Imaging 2012;35:1290–1299. © 2012 Wiley Periodicals, Inc.

Despite the wide use of live supervision in marriage and family therapy training, there have been no randomized trials comparing different variations of the practice. This randomized trial of 86 clients was designed to measure client satisfaction after an initial therapy session under two conditions: meeting the supervision team behind the observation mirror or not meeting the team. A mixed linear model analysis of covariance was used to examine the relationship between ‘meeting the team’ versus ‘not meeting the team’ and client satisfaction. There were no statistically significant differences in client satisfaction based on whether clients met the team or not. There was a trend toward greater satisfaction with the therapy session among clients who did not meet the supervision team.

We presented principles for the planning of factorial experiments concerned with protection of the environment, carried out on heterogeneous experimental material or, for example, in the case of non-uniform or, particularly, low levels of disease or pest infection. A block design with nested rows and columns (NRC) is proposed. We supposed that there are a levels of experimental factor A and b levels of experimental factor B. Hence ab experimental combinations and one control treatment are applied to experimental units. We assumed a mixed linear model resulting from randomization of blocks, rows and columns. We proposed stratum analysis and obtained the efficiency factors of estimation of treatment contrasts in the strata. We described a NRC design having certain properties. We considered type S designs, designs possessing C-property and presented constructions of type S NRC designs and NRC designs possessing C-property. A necessary and sufficient condition is obtained for a type S NRC design to be design possessing C-property. Copyright © 2009 John Wiley & Sons, Ltd.

The partial rust resistance genes Lr34 and Sr2 have been used extensively in wheat (Triticum aestivum L.) improvement, as they confer exceptional durability. Interestingly, the resistance of Lr34 is associated with the expression of leaf tip necrosis (LTN) and Sr2 with pseudo-black chaff (PBC). Genome-wide association mapping using CIMMYT's stem rust resistance screening nursery (SRRSN) wheat lines was done to identify genotyping-by-sequencing (GBS) markers linked to LTN and PBC. Phenotyping for these traits was done in Ithaca, New York (fall 2011); Njoro, Kenya (main and off-seasons, 2012), and Wellington, India (winter, 2013). Using the mixed linear model (MLM), 18 GBS markers were significantly associated with LTN. While some markers were linked to loci where the durable leaf rust resistance genes Lr34 (7DS), Lr46 (1BL), and Lr68 (7BL) were mapped, significant associations were also detected with other loci on 2BL, 5B, 3BS, 4BS, and 7BS. Twelve GBS markers linked to the Sr2 locus (3BS) and loci on 2DS, 4AL, and 7DS were significantly associated with PBC. This study provides insight into the complex genetic control of LTN and PBC. Further efforts to validate and study these loci might aid in determining the nature of their association with durable resistance.

Malaria is a cause of anemia, and may be associated with impaired physical growth in early childhood. In the context of lipid-based nutrient supplementation (LNS) that provided different doses of zinc and treatment for malaria, diarrhea and fever, the association of malaria with physical growth and hemoglobin concentration (Hb) in young Burkinabe children was assessed. Children (n=1960) received 20 g LNS daily and were visited weekly for morbidity assessment from 9-18 mo of age. At baseline and during the 9-mo follow-up, children were treated for confirmed malaria based on rapid diagnostic test (RDT), reported fever and diarrhea. At 9 and 18 mo, length, weight and Hb were assessed. A mixed linear model was used to examine the association. At 9 mo, 59% of children were RDT positive, 91% had Hb < 110 g/L, and 23% and 17% had length-for-age z-score (LAZ) and weight-for-length z-score (WLZ) < - 2.0 SD, respectively. During the 9-mo of follow-up, 27% of children had no malaria episode, 34% had one episode and ...

Background: The aim of this study was to compare the reproducibility and sensitivity of four commonly used methods for QT interval assessment when applied to ECG data obtained after infusion of ibutilide. Methods: Four methods were compared: (1) 12-lead simultaneous ECG (12-SIM), (2) lead II ECG (LEAD II), both measured on a digitizing board, (3) 3-LEAD ECG using a manual tangential method, and (4) a computer-based, proprietary algorithm, 12SL™ ECG Analysis software (AUT). QT intervals were measured in 10 healthy volunteers at multiple time points during 24 hours at baseline and after single intravenous doses of ibutilide 0.25 and 0.5 mg. Changes in QT interval from baseline were calculated and compared across ECG methods, using Bland–Altman plots. Variability was studied using a mixed linear model. Results: Baseline QT values differed between methods (range 376–395 ms), mainly based on the number of leads incorporated into the measurement, with LEAD II and 3-LEAD providing the shortest intervals. The 3-LEAD generated the largest QT change from baseline, whereas LEAD II and 12-SIM generated essentially identical result within narrow limits of agreement (0.4 ms mean difference, 95% confidence interval ± 20.5 ms). Variability with AUT (standard deviation 15.8 ms for within-subject values) was clearly larger than with 3-LEAD, LEAD II, and 12-SIM (9.6, 10.0, and 11.3 ms). Conclusion: This study demonstrated significant differences among four commonly used methods for QT interval measurement after pharmacological prolongation of cardiac repolarization. Observed large differences in variability of measurements will have a substantial impact on the sample size required to detect QT prolongation in the range that is currently advised in regulatory guidance.

Large governmental surveys typically provide accurate national statistics. To decrease the mean squared error of estimates for small areas, i.e., domains in which the sample size is small, auxiliary variables from administrative records are often used as covariates in a mixed linear model. It is generally assumed that the auxiliary information is available for every small area. In many cases, though, such information is available for only some of the small areas, either from another survey or from a previous administration of the same survey. The authors propose and study small area estimators that use multivariate models to combine information from several surveys. They discuss computational algorithms, and a simulation study indicates that if quantities in the different surveys are sufficiently correlated, substantial gains in efficiency can be achieved.

Summary Determination of reasonable non-informative priors in multiparameter problems is not easy; common non-informative priors, such as Jeffrey's prior, can have features that have an unexpectedly dramatic effect on the posterior. In recognition of this problem Berger and Bernardo (Bayesian Statistics IV. Oxford University Press, Oxford, UK, pp. 35–70, 1992), proposed the Reference Prior approach to the development of non-informative priors. In the present paper the reference priors of Berger and Bernardo (1992) are derived for the mixed linear model. In spite of these difficulties, there is growing evidence, mainly through examples that reference priors provide ‘sensible’ answers from a Bayesian point of view. We also examine whether the reference priors satisfy the probability-matching criterion. The theory and results are applied to a real problem consisting of 879 weaning weight records, from the progeny of 17 sires. These important aspects are explored via Monte Carlo simulations. Zusammenfassung Reference und Probability-Matching Priors in Bayesian Analysen von gemischten linearen Modellen Die Festlegung von vernunftigen Non-Informative Priors in Multi-Paramter Analysen ist nicht leicht; gewohnliche Non-Informative Priors, wie beispielsweise Jeffrey's Priors, konnen unerwartete dramatische Effekte auf die Losungen haben. Zur Losung dieses Problems schlagen Berger and Bernardo (Bayesian Statistics IV. Oxford University Press, Oxford, UK, pp. 35–70, 1992) den Reference Prior Ansatz zur Entwicklung von Non-Informative Priors vor. In der vorliegenden Untersuchung werden die von Berger and Bernardo (1992) vorgeschlagenen Reference Priors in linearen gemischten Modellen angewandt. Trotz der bekannten Schwierigkeiten gibt es hauptsachlich anhand von Beispielen mehr und mehr Anhaltspunkte, dass die Reference Priors aus der Sicht von Bayesians zu brauchbaren Antworten fuhren. Es wurde auch untersucht, ob diese Reference Priors den Probability-Matching Kriterien genugen. Die Theorie und die Ergebnisse sind an einem Beispiel mit 879 Datensatzen mit Absatzgewichten von Schafen, die von 17 Bocken abstammen, verifiziert worden. Die wichtigen Aspekte sind mittels Monte Carlo Simulation untersucht worden.

Objectives: Recommendations on wholegrain (WG) consumption are widespread but rarely quantitative. This work attempted to systematically review published human studies to quantify the daily intake of WG associated to favourable health outcomes. Results related to cardiovascular diseases (CVD) and type-2 diabetes (T2D) are presented here. Methods: Databases were searched from 1993 to 2012. Retrieved papers were screened by 3 PhDs. Six articles were selected for each outcome. A meta-analysis was done using multivariate-adjusted risk ratios of CVD comparing highest and lowest WG intake levels. Then, meta-regressions were performed on CVD and T2D rates relative to WG amounts by using a hierarchical mixed linear model. Results: First, we confirmed a significant inverse association between WG intake and CVD risk (overall RR = 0.84; p=0.004). Although quantitative meta-regression failed to demonstrate a significant relationship between WG intake and CVD rate, a significant relationship was observed for T2D (p

In this article, we estimate heritability or intraclass correlation in a mixed linear model having two sources of variation. In most applications, the commonly used restricted maximum likelihood (REML) estimator can only be obtained via an iterative approach. In some cases, the algorithm used to compute REML estimates may be slow or may even fail to converge. We develop a set of closed-form approximations to the REML estimator, and the performance of these estimators is compared with that of the REML estimator. We provide guidelines regarding how to choose the estimator that best approximates the REML estimator. Examples presented in the article suggest that the closed-form estimators compete with and, in some cases, outperform the REML estimator.