A mixed model QTL analysis for sugarcane multiple-harvest-location trial data

Sugarcane-breeding programs take at least 12 years to develop new commercial cultivars. Molecular markers offer a possibility to study the genetic architecture of quantitative traits in sugarcane, and they may be used in marker-assisted selection to speed up artificial selection. Although the performance of sugarcane progenies in breeding programs are commonly evaluated across a range of locations and harvest years, many of the QTL detection methods ignore two- and three-way interactions between QTL, harvest, and location. In this work, a strategy for QTL detection in multi-harvest-location trial data, based on interval mapping and mixed models, is proposed and applied to map QTL effects on a segregating progeny from a biparental cross of pre-commercial Brazilian cultivars, evaluated at two locations and three consecutive harvest years for cane yield (tonnes per hectare), sugar yield (tonnes per hectare), fiber percent, and sucrose content. In the mixed model, we have included appropriate (co)variance structures for modeling heterogeneity and correlation of genetic effects and non-genetic residual effects. Forty-six QTLs were found: 13 QTLs for cane yield, 14 for sugar yield, 11 for fiber percent, and 8 for sucrose content. In addition, QTL by harvest, QTL by location, and QTL by harvest by location interaction effects were significant for all evaluated traits (30 QTLs showed some interaction, and 16 none). Our results contribute to a better understanding of the genetic architecture of complex traits related to biomass production and sucrose content in sugarcane.

Impact of FLT3 Internal Tandem Duplication on the Outcome of Related and Unrelated Hematopoietic Transplantation for Adult Acute Myeloid Leukemia in First Remission: A Retrospective Analysis

Purpose Patients with acute myeloid leukemia (AML) and FLT3/internal tandem duplication (FLT3/ITD) have poor prognosis if treated with chemotherapy only. Whether this alteration also affects outcome after allogeneic hematopoietic stem-cell transplantation (HSCT) remains uncertain. Patients and Methods We analyzed 206 patients who underwent HLA-identical sibling and matched unrelated HSCTs reported to the European Group for Blood and Marrow Transplantation with a diagnosis of AML with normal cytogenetics and data on FLT3/ITD (present: n = 120, 58%; absent: n = 86, 42%). Transplantations were performed in first complete remission (CR) after myeloablative conditioning. Results Compared with FLT3/ITD-negative patients, FLT3/ITD-positive patients had higher median leukocyte count at diagnosis (59 v 21 x 10(9)/L; P < .001) and shorter interval from CR to transplantation (87 v 99 days; P = .04). Other characteristics were similar in the two groups. At 2 years, relapse incidence (RI; +/- standard deviation) was higher (30% +/- 5% v 16% +/- 5%; P = .006) and leukemia-free survival (LFS) lower (58% +/- 5% v 71% +/- 6%; P = .04) in FLT3/ITD-positive compared with FLT3/ITD-negative patients. In multivariate analyses, FLT3/ITD led to increased RI (hazard ratio [HR], 3.4; 95% CI, 1.46 to 7.94; P = .005), as did older age, female sex, shorter interval between CR and transplantation, and higher number of chemotherapy courses before achieving CR. FLT3/ITD positivity was associated with decreased LFS (HR, 0.37; 95% CI, 0.19 to 0.73; P = .002), along with older age and higher number of chemotherapy courses before achieving CR. Conclusion FLT3/ITD adversely affected the outcome of HSCT in the same direction it does after chemotherapy; despite this, more than half of the patients harboring this mutation who received transplants were alive and leukemia free at 2 years. To further improve the results, use of FLT3 inhibitors before or after HSCT deserves investigation.

Bioelectrical Impedance Analysis and Skinfold Thickness Sum in Assessing Body Fat Mass of Renal Dialysis Patients

Objective: In chronic renal failure patients under hemodialysis (HD) treatment, the availability of simple, safe, and effective tools to assess body composition enables evaluation of body composition accurately, in spite of changes in body fluids that occur in dialysis therapy, thus contributing to planning and monitoring of nutritional treatment. We evaluated the performance of bioelectrical impedance analysis (BIA) and the skinfold thickness sum (SKF) to assess fat mass (FM) in chronic renal failure patients before (BHD) and after (AHD) HD, using air displacement plethysmography (ADP) as the standard method. Design: This single-center cross-sectional trial involved comparing the FM of 60 HD patients estimated BHD and AHD by BIA (multifrequential; 29 women, 31 men) and by SKF with those estimated by the reference method, ADP. Body fat-free mass (FFM) was also obtained by subtracting the total body fat from the individual total weight. Results: Mean estimated FM (kg [%]) observed by ADP BHD was 17.95 +/- 0.99 kg (30.11% +/- 1.30%), with a 95% confidence interval (CI) of 16.00 to 19.90 (27.56 to 32.66); mean estimated FM observed AHD was 17.92 +/- 1.11 kg (30.04% +/- 1.40%), with a 95% CI of 15.74 to 20.10 (27.28 to 32.79). Neither study period showed a difference in FM and FFM (for both kg and %) estimates by the SKF method when compared with ADP; however, the BIA underestimated the FM and overestimated the FFM (for both kg and %) when compared with ADP. Conclusion: The SKF, but not the BIA, method showed results similar to ADP and can be considered adequate for FM evaluation in HD patients. (C) 2012 by the National Kidney Foundation, Inc. All rights reserved.

Similar health benefits of endurance and high-intensity interval training in obese children

Purpose: To compare two modalities of exercise training (i.e., Endurance Training [ET] and High-Intensity Interval Training [HIT]) on health-related parameters in obese children aged between 8 and 12 years. Methods: Thirty obese children were randomly allocated into either the ET or HIT group. The ET group performed a 30 to 60-minute continuous exercise at 80% of the peak heart rate (HR). The HIT group training performed 3 to 6 sets of 60-s sprint at 100% of the peak velocity interspersed by a 3-min active recovery period at 50% of the exercise velocity. HIT sessions last similar to 70% less than ET sessions. At baseline and after 12 weeks of intervention, aerobic fitness, body composition and metabolic parameters were assessed. Results: Both the absolute (ET: 26.0%; HIT: 19.0%) and the relative VO2 peak (ET: 13.1%; HIT: 14.6%) were significantly increased in both groups after the intervention. Additionally, the total time of exercise (ET: 19.5%; HIT: 16.4%) and the peak velocity during the maximal graded cardiorespiratory test (ET: 16.9%; HIT: 13.4%) were significantly improved across interventions. Insulinemia (ET: 29.4%; HIT: 30.5%) and HOMA-index (ET: 42.8%; HIT: 37.0%) were significantly lower for both groups at POST when compared to PRE. Body mass was significantly reduced in the HIT (2.6%), but not in the ET group (1.2%). A significant reduction in BMI was observed for both groups after the intervention (ET: 3.0%; HIT: 5.0%). The responsiveness analysis revealed a very similar pattern of the most responsive variables among groups. Conclusion: HIT and ET were equally effective in improving important health related parameters in obese youth.

A multicenter, multinational analysis of mitomycin C in refractory metastatic colorectal cancer

Background: A considerable number of metastatic colorectal cancer (mCRC) patients who progress on standard treatment with 5-fluorouracil (5FU), oxaliplatin, irinotecan and monoclonal antibodies, still have adequate performance status and desire further treatment. Mitomycin C (MMC) has been widely used in this context, and despite good tolerability, there are doubts regarding its true benefit. Methods: In order to assess the activity of MMC in the refractory mCRC setting, we retrospectively evaluated 109 heavily pre-treated patients who received MMC as single agent or in combination for mCRC at three different institutions in two countries. Results: Median patient's age was 54 years old, 57% were male and 94% had performance status ECOG 0 or 1. MMC was used in second line in 11%, third line in 38% and fourth line or beyond in 51% of patients. 58% received MMC combinations, mainly with capecitabine. Grade 3 or 4 toxicity was observed in 5% of patients and 6% required dose reductions. Median time to treatment failure (TTF) was 1.7 months with MMC and 3.6 months on the regimen prior to MMC, with a ratio between these TTF below 1 in 82% of patients. Median survival was only 4.5 months (95% confidence interval (CI) of 3.48-5.56). Conclusions: This retrospective data represent the largest reported series of unselected refractory mCRC patients treated with MMC. The median survival of 4.5 months is similar to the survival expected for best supportive care. This lack of activity strongly suggests that MMC should not be routinely used in refractory mCRC. (C) 2012 Elsevier Ltd. All rights reserved.

Mechanical analysis of conventional and small diameter conical implant abutments

PURPOSE. The aim of the present study was to evaluate if a smaller morse taper abutment has a negative effect on the fracture resistance of implant-abutment connections under oblique compressive loads compared to a conventional abutment MATERIALS AND METHODS. Twenty morse taper conventional abutments (4.8 mm diameter) and smaller abutments (3.8 mm diameter) were tightened (20 Ncm) to their respective implants (3.5 x 11 mm) and after a 10 minute interval, implant/abutment assemblies were subjected to static compressive test, performed in a universal test machine with 1 mm/min displacement, at 45 degrees inclination. The maximum deformation force was determined. Data were statistically analyzed by student t test. RESULTS. Maximum deformation force of 4.8 mm and 3.8 mm abutments was approximately 95.33 kgf and 95.25 kgf, respectively, but no fractures were noted after mechanical test. Statistical analysis demonstrated that the evaluated abutments were statistically similar (P=.230). CONCLUSION. Abutment measuring 3.8 mm in diameter (reduced) presented mechanical properties similar to 4.8 mm (conventional) abutments, enabling its clinical use as indicated. [J Adv Prosthodont 2012;4:158-61]

Association analysis of clinical aspects and vitamin D receptor gene polymorphism with external apical root resorption in orthodontic patients

Introduction: Vitamin D is responsible for the regulation of certain genes at the transcription level, via interaction with the vitamin D receptor, and influences host immune responses and aspects of bone development, growth, and homeostasis. Our aim was to investigate the association of TaqI vitamin D receptor gene polymorphism with external apical root resorption during orthodontic treatment. Methods: Our subjects were 377 patients with Class II Division 1 malocclusion, divided into 3 groups: (1) 160 with external apical root resorption <= 1.43 mm, (2) 179 with external apical root resorption >1.43 mm), and (3) 38 untreated subjects. External apical root resorption of the maxillary incisors was evaluated on periapical radiographs taken before and after 6 months of treatment. After DNA collection and purification, vitamin D receptor TaqI polymorphism analysis was performed by polymerase chain reaction-restriction fragment length polymorphism. Univariate and multivariate analyses were performed to verify the association of clinical and genetic variables with external apical root resorption (P <0.05). Results: There was a higher proportion of external apical root resorption in orthodontically treated patients compared with the untreated subjects. In patients orthodontically treated, age higher than 14 years old, initial size of the maxillary incisor root superior to 30 mm, and premolar extraction were associated with increased external apical root resorption. Genotypes containing the C allele were weakly associated with protection against external apical root resorption (CC + CT x TT [odds ratio, 0.29; 95% confidence interval, 0.07-1.23; P = 0.091]) when treated orthodontic patients were compared to untreated individuals. Conclusions: Clinical factors and vitamin D receptor TaqI polymorphism were associated with external apical root resorption in orthodontic patients. (Am J Orthod Dentofacial Orthop 2012; 142: 339-47)

Pre- and Postoperative Quantitative Analysis of Contour Abnormalities in Graves Upper Eyelid Retraction

Purpose: One of the most common problems of the surgical management of Graves upper eyelid retraction is the occurrence of eyelid contour abnormalities. In the present study, the postoperative contour of a large sample of eyelids of patients with Graves orbitopathy was measured. Methods: The postoperative upper eyelid contour of 62 eyes of 43 patients with Graves orbitopathy was subjectively classified by 3 experienced surgeons in 3 categories: poor, fair, and good. The shape of the eyelid contours in each category was then measured with a recently developed custom-made software by measuring multiple midpupil eyelid distances each 15 degrees along the palpebral fissure. The upper eyelid contour of 60 normal subjects was also quantified as a control group. Results: The mean ratio between the sum of the lateral and medial midpupil eyelid distances (lateral/medial ratio) was 1.10 +/- 0.11 standard deviation in controls and 1.15 +/- 0.13 standard deviation in patients. Postoperatively, the mean midpupil eyelid distance at 90 degrees was 4.16 +/- 1.13 mm standard deviation. The distribution lateral/medial ratios of the eyelids judged as having good contours was similar to the distribution of the controls with a modal value centered on the interval between 1.0 and 1.10. The distribution of lateral/medial ratios of the eyelids judged as having poor contour was bimodal, with eyelids with low and high lateral/medial ratios. Low lateral/medial ratios occurred when there was a lateral overcorrection, giving the eyelid a flat or a medial ptosis appearance. High lateral/medial ratios were due to a central or medial overcorrection or a lateral peak maintenance. Conclusions: Postoperative upper eyelid contour abnormalities can be quantified by comparing the sum of multiple midpupil eyelid distances of the lateral and medial sectors of the eyelid. Low and high lateral/medial ratios are anomalous and judged as unpleasant. (Ophthal Plast Reconstr Surg 2012;28:429-433)

Aging reduces complexity of heart rate variability assessed by conditional entropy and symbolic analysis

Increasing age is associated with a reduction in overall heart rate variability as well as changes in complexity of physiologic dynamics. The aim of this study was to verify if the alterations in autonomic modulation of heart rate caused by the aging process could be detected by Shannon entropy (SE), conditional entropy (CE) and symbolic analysis (SA). Complexity analysis was carried out in 44 healthy subjects divided into two groups: old (n = 23, 63 +/- A 3 years) and young group (n = 21, 23 +/- A 2). It was analyzed SE, CE [complexity index (CI) and normalized CI (NCI)] and SA (0V, 1V, 2LV and 2ULV patterns) during short heart period series (200 cardiac beats) derived from ECG recordings during 15 min of rest in a supine position. The sequences characterized by three heart periods with no significant variations (0V), and that with two significant unlike variations (2ULV) reflect changes in sympathetic and vagal modulation, respectively. The unpaired t test (or Mann-Whitney rank sum test when appropriate) was used in the statistical analysis. In the aging process, the distributions of patterns (SE) remain similar to young subjects. However, the regularity is significantly different; the patterns are more repetitive in the old group (a decrease of CI and NCI). The amounts of pattern types are different: 0V is increased and 2LV and 2ULV are reduced in the old group. These differences indicate marked change of autonomic regulation. The CE and SA are feasible techniques to detect alteration in autonomic control of heart rate in the old group.

Effect of continuous and interval exercise training on the PETCO2 response during a graded exercise test in patients with coronary artery disease

OBJECTIVE: The purpose of this study was to evaluate the following: 1) the effects of continuous exercise training and interval exercise training on the end-tidal carbon dioxide pressure (PETCO2) response during a graded exercise test in patients with coronary artery disease; and 2) the effects of exercise training modalities on the association between PETCO2 at the ventilatory anaerobic threshold (VAT) and indicators of ventilatory efficiency and cardiorespiratory fitness in patients with coronary artery disease. METHODS: Thirty-seven patients (59.7 +/- 1.7 years) with coronary artery disease were randomly divided into two groups: continuous exercise training (n = 20) and interval exercise training (n = 17). All patients performed a graded exercise test with respiratory gas analysis before and after three months of the exercise training program to determine the VAT, respiratory compensation point (RCP) and peak oxygen consumption. RESULTS: After the interventions, both groups exhibited increased cardiorespiratory fitness. Indeed, the continuous exercise and interval exercise training groups demonstrated increases in both ventilatory efficiency and PETCO2 values at VAT, RCP, and peak of exercise. Significant associations were observed in both groups: 1) continuous exercise training (PETCO(2)VAT and cardiorespiratory fitness r = 0.49; PETCO(2)VAT and ventilatory efficiency r = -0.80) and 2) interval exercise training (PETCO(2)VAT and cardiorespiratory fitness r = 0.39; PETCO(2)VAT and ventilatory efficiency r = -0.45). CONCLUSIONS: Both exercise training modalities showed similar increases in PETCO2 levels during a graded exercise test in patients with coronary artery disease, which may be associated with an improvement in ventilatory efficiency and cardiorespiratory fitness.

Pedigree analysis and inbreeding depression on growth traits in Brazilian Marchigiana and Bonsmara breeds

The study of population structure by pedigree analysis is useful to identify important circumstances that affect the genetic history of populations. The intensive use of a small number of superior individuals may reduce the genetic diversity of populations. This situation is very common for the beef cattle breeds. Therefore, the objectives of the present study were to analyze the pedigree and possible inbreeding depression on traits of economic interest in the Marchigiana and Bonsmara breeds and to test the inclusion of the individual inbreeding coefficient (F-i) or individual increases in inbreeding coefficient (Delta F-i) in the genetic evaluation model for the quantification of inbreeding depression. The complete pedigree file of the Marchigiana breed included 29,411 animals born between 1950 and 2003. For the Bonsmara breed, the pedigree file included 18,695 animals born between 1988 and 2006. Only animals with at least 2 equivalent generations of known pedigree were kept in the analyses of inbreeding effect on birth weight, weaning weight measured at about 205 d, and BW at 14 mo in the Marchigiana breed, and on birth weight, weaning weight, and scro-tal circumference measured at 12 mo in the Bonsmara breed. The degree of pedigree knowledge was greater for Marchigiana than for Bonsmara animals. The average generation interval was 7.02 and 3.19 for the Marchigiana and Bonsmara breed, respectively. The average inbreeding coefficient was 1.33% for Marchigiana and 0.26% for Bonsmara. The number of ancestors explaining 50% of the gene pool and effective population size computed via individual increase in coancestry were 13 and 97.79 for Marchigiana and 41 and 54.57 for Bonsmara, respectively. These estimates indicate reduction in genetic variability in both breeds. Inbreeding depression was observed for most of the growth traits. The model including Delta F-i can be considered more adequate to quantify inbreeding depression. The inclusion of F-i or Delta F-i in the genetic evaluation model may not result in better fit to the data. A genetic evaluation with simultaneous estimation of inbreeding depression can be performed in Marchigiana and Bonsmara breeds, providing additional information to producers and breeders.

Influence of Alloying Elements Upon the Solidification Interval of CA6NM Cast Martensitic Stainless Steel

The influence of different Cr and C contents upon the solidification interval of ASTM A352M-06 Grade CA6NM cast martensitic stainless steel has been investigated using computational thermodynamics, and checked against DTA measurements in samples taken from 13 large cast parts, in order to identify potential sources for improvement on the part castability. Calculation results suggest, indeed, that this would be the case for C: when its content increases from 0.018 to 0.044 wt.% C (within the allowed range in the alloy specification), the solidification intervals increases from 25 to 43 K, which suggests improved castability with decreasing C contents. DTA results, however, do not support this prediction, showing a fairly constant solidification interval around 23 K for all investigated samples. The results are discussed both regarding the impact in alloy processing and the fitness of the existing databases to reproduce experimental results in these limiting cases.

Why Are Women With Cervical Cancer Not Being Diagnosed in Preinvasive Phase? An Analysis of Risk Factors Using a Hierarchical Model

Objective: To assess the risk factors for delayed diagnosis of uterine cervical lesions. Materials and Methods: This is a case-control study that recruited 178 women at 2 Brazilian hospitals. The cases (n = 74) were composed of women with a late diagnosis of a lesion in the uterine cervix (invasive carcinoma in any stage). The controls (n = 104) were composed of women with cervical lesions diagnosed early on (low-or high-grade intraepithelial lesions). The analysis was performed by means of logistic regression model using a hierarchical model. The socioeconomic and demographic variables were included at level I (distal). Level II (intermediate) included the personal and family antecedents and knowledge about the Papanicolaou test and human papillomavirus. Level III (proximal) encompassed the variables relating to individuals' care for their own health, gynecologic symptoms, and variables relating to access to the health care system. Results: The risk factors for late diagnosis of uterine cervical lesions were age older than 40 years (odds ratio [OR] = 10.4; 95% confidence interval [CI], 2.3-48.4), not knowing the difference between the Papanicolaou test and gynecological pelvic examinations (OR, = 2.5; 95% CI, 1.3-4.9), not thinking that the Papanicolaou test was important (odds ratio [OR], 4.2; 95% CI, 1.3-13.4), and abnormal vaginal bleeding (OR, 15.0; 95% CI, 6.5-35.0). Previous treatment for sexually transmissible disease was a protective factor (OR, 0.3; 95% CI, 0.1-0.8) for delayed diagnosis. Conclusions: Deficiencies in cervical cancer prevention programs in developing countries are not simply a matter of better provision and coverage of Papanicolaou tests. The misconception about the Papanicolaou test is a serious educational problem, as demonstrated by the present study.

DNA repair gene excision repair cross complementing-group 1 (ERCC1) in head and neck squamous cell carcinoma: analysis of methylation and polymorphism (G19007A), protein expression and association with epidemiological and clinicopathological factors

Aims: To evaluate the associations of excision repair cross complementing-group 1 (ERCC1) (DNA repair protein) (G19007A) polymorphism, methylation and immunohistochemical expression with epidemiological and clinicopathological factors and with overall survival in head and neck squamous cell carcinoma (HNSCC) patients. Methods and results: The study group comprised 84 patients with HNSCC who underwent surgery and adjuvant radiotherapy without chemotherapy. Bivariate and multivariate analyses were used. The allele A genotype variant was observed in 79.8% of the samples, GG in 20.2%, GA in 28.6% and AA in 51.2%. Individuals aged more than 45 years had a higher prevalence of the allelic A variant and a high (83.3%) immunohistochemical expression of ERCC1 protein [odds ratio (OR) = 4.86, 95% confidence interval (CI): 1.2-19.7, P = 0.027], which was also high in patients with advanced stage (OR= 5.04, 95% CI: 1.07-23.7, P = 0.041). Methylated status was found in 51.2% of the samples, and was higher in patients who did not present distant metastasis (OR = 6.67, 95% CI: 1.40-33.33, P = 0.019) and in patients with advanced stage (OR = 5.04, 95% CI: 1.07-23.7, P = 0.041). At 2 and 5 years, overall survival was 55% and 36%, respectively (median = 30 months). Conclusion: Our findings may reflect a high rate of DNA repair due to frequent tissue injury during the lifetime of these individuals, and also more advanced disease presentation in this population with worse prognosis.

Impact of pretransplant minimal residual disease after cord blood transplantation for childhood acute lymphoblastic leukemia in remission: an Eurocord, PDWP-EBMT analysis

To address the prognostic value of minimal residual disease (MRD) before unrelated cord blood transplantation (UCBT) in children with acute lymphoblastic leukemia (ALL), we analyzed 170 ALL children transplanted in complete remission (CR) after myeloablative conditioning regimen. In all, 72 (43%) were in first CR (CR1), 77 (45%) in second CR (CR2) and 21 (12%) in third CR (CR3). The median interval from MRD quantification to UCBT was 18 days. All patients received single-unit UCBT. Median follow-up was 4 years. Cumulative incidence (CI) of day-60 neutrophil engraftment was 85%. CI of 4 years relapse was 30%, incidence being lower in patients with negative MRD before UCBT (hazard ratio (HR) = 0.4, P = 0.01) and for those transplanted in CR1 and CR2 (HR = 0.3, P = 0.002). Probability of 4 years leukemia-free survival (LFS) was 44%, (56, 44 and 14% for patients transplanted in CR1, CR2 and CR3, respectively (P = 0.0001)). Patients with negative MRD before UCBT had better LFS after UCBT compared with those with positive MRD (54% vs 29%; HR = 2, P = 0.003). MRD assessment before UCBT for children with ALL in remission allows identifying patients at higher risk of relapse after transplantation. Approaches that may decrease relapse incidence in children given UCBT with positive MRD should be investigated to improve final outcomes. Leukemia (2012) 26, 2455-2461; doi:10.1038/leu.2012.123