Alternative strategies for deciphering the genetic architecture of childhood Pre-B acute lymphoblastic leukemia

La leucémie lymphoblastique aigüe (LLA) est une maladie génétique complexe. Malgré que cette maladie hématologique soit le cancer pédiatrique le plus fréquent, ses causes demeurent inconnues. Des études antérieures ont démontrées que le risque à la LLA chez l’enfant pourrait être influencé par des gènes agissant dans le métabolisme des xénobiotiques, dans le maintient de l’intégrité génomique et dans la réponse au stress oxydatif, ainsi que par des facteurs environnementaux. Au cours de mes études doctorales, j’ai tenté de disséquer davantage les bases génétiques de la LLA de l’enfant en postulant que la susceptibilité à cette maladie serait modulée, au moins en partie, par des variants génétiques agissant dans deux voies biologiques fondamentales : le point de contrôle G1/S du cycle cellulaire et la réparation des cassures double-brin de l’ADN. En utilisant une approche unique reposant sur l’analyse d’une cohorte cas-contrôles jumelée à une cohorte de trios enfants-parents, j’ai effectué une étude d’association de type gènes/voies biologiques candidats. Ainsi, j’ai évaluer le rôle de variants provenant de la séquence promotrice de 12 gènes du cycle cellulaire et de 7 gènes de la voie de réparation de l’ADN, dans la susceptibilité à la LLA. De tels polymorphismes dans la région promotrice (pSNPs) pourraient perturber la liaison de facteurs de transcription et mener à des différences dans les niveaux d’expression des gènes pouvant influencer le risque à la maladie. En combinant différentes méthodes analytiques, j’ai évalué le rôle de différents mécanismes génétiques dans le développement de la LLA chez l’enfant. J’ai tout d’abord étudié les associations avec gènes/variants indépendants, et des essaies fonctionnels ont été effectués afin d’évaluer l’impact des pSNPs sur la liaison de facteurs de transcription et l’activité promotrice allèle-spécifique. Ces analyses ont mené à quatre publications. Il est peu probable que ces gènes de susceptibilité agissent seuls; j’ai donc utilisé une approche intégrative afin d’explorer la possibilité que plusieurs variants d’une même voie biologique ou de voies connexes puissent moduler le risque de la maladie; ces travaux ont été soumis pour publication. En outre, le développement précoce de la LLA, voir même in utero, suggère que les parents, et plus particulièrement la mère, pourraient jouer un rôle important dans le développement de cette maladie chez l’enfant. Dans une étude par simulations, j’ai évalué la performance des méthodes d’analyse existantes de détecter des effets fœto-maternels sous un design hybride trios/cas-contrôles. J’ai également investigué l’impact des effets génétiques agissant via la mère sur la susceptibilité à la LLA. Cette étude, récemment publiée, fût la première à démontrer que le risque de la leucémie chez l’enfant peut être modulé par le génotype de sa mère. En conclusions, mes études doctorales ont permis d’identifier des nouveaux gènes de susceptibilité pour la LLA pédiatrique et de mettre en évidence le rôle du cycle cellulaire et de la voie de la réparation de l’ADN dans la leucémogenèse. À terme, ces travaux permettront de mieux comprendre les bases génétiques de la LLA, et conduiront au développement d’outils cliniques qui amélioreront la détection, le diagnostique et le traitement de la leucémie chez l’enfant.

Genotype effect on carcass and meat quality of lambs finished in irrigated pastures in the semiarid Northeastern Brazil

The aim of this study was to compare four genetic groups of sheep on the carcass and meat quality traits. Thirty-three contemporary and unrelated male lambs, all of single birth were used in the experiment, being thirteen from the Santa Inês (SI) breed, seven from the Brazilian Somali breed (BS), six from the Morada Nova (MN) breed and seven from the ½ Dorper - ½ Morada Nova (F1) crossbreed. The genotypes SI, BS and F1 presented similar performances in relation to hot and cold carcass weights, which values were 10.76±0.53kg and 10.46±0.52kg for SI, 9.20±0.73kg and 8.99±0.71kg for BS, and 9.35±0.73kg and 9.13±0.71kg for F1, respectively. The BS had a better hot carcass yield (47.10±0.88%) and cold carcass yield (46.00±0.87%). Better carcass conformation was observed in SI and F1 (2.73±0.12 and 2.50±0.17, respectively) while the BS presented a better finishing (3.29±0.20). The average for the rib eye area (REA) was 9.94±0.49cm², 8.66±0.67cm², 7.18±0.72cm² and 9.8±0.67cm², and for the carcass compactness index (CCI) it was 0.17±0.01kg/cm, 0.17±0.01kg/cm, 0.11±0.01kg/cm and 0.16±0,01kg/cm, for SI, SB, MN and F1, respectively. There were no significant differences between SI, BS and F1 regarding REA and CCI. Although, in general, the MN presented a relatively lower performance than the other genotypes, this breed had similar carcass yields and fat thickness when compared to SI and F1 and similar conformation and REA in comparison to the BS. Regarding meat quality, no differences were observed between genotypes, except for redness and cooking losses. It is concluded that no one group had a higher or lower performance in all traits analyzed. Moreover, for the management conditions employed in this study, there was evidence of greater specialization in meat production for genotypes SI, BS and F1 when compared to MN, although there are no substantial differences between the four groups regarding meat quality.

Enhancing agrobacterium-mediated transformation efficiency of sugarcane : progress towards an efficient, genotype-independent method

Several key issues need to be resolved before an efficient and reproducible Agrobacterium-mediated sugarcane transformation method can be developed for a wider range of sugarcane cultivars. These include loss of morphogenetic potential in sugarcane cells after Agrobacterium-mediated transformation, effect of exposure to abiotic stresses during in vitro selection, and most importantly the hypersensitive cell death response of sugarcane (and other nonhost plants) to Agrobacterium tumefaciens. Eight sugarcane cultivars (Q117, Q151, Q177, Q200, Q208, KQ228, QS94-2329, and QS94-2174) were evaluated for loss of morphogenetic potential in response to the age of the culture, exposure to Agrobacterium strains, and exposure to abiotic stresses during selection. Corresponding changes in the polyamine profiles of these cultures were also assessed. Strategies were then designed to minimize the negative effects of these factors on the cell survival and callus proliferation following Agrobacterium-mediated transformation. Some of these strategies, including the use of cell death protector genes and regulation of intracellular polyamine levels, will be discussed.

Effect of C282Y Genotype on Self-Reported Musculoskeletal Complications in Hereditary Hemochromatosis

OBJECTIVE: Arthropathy that mimics osteoarthritis (OA) and osteoporosis (OP) is considered a complication of hereditary hemochromatosis (HH). We have limited data comparing OA and OP prevalence among HH patients with different hemochromatosis type 1 (HFE) genotypes. We investigated the prevalence of OA and OP in patients with HH by C282Y homozygosity and compound heterozygosity (C282Y/H63D) genotype. METHODS: A total of 306 patients with HH completed a questionnaire. Clinical and demographic characteristics and presence of OA, OP and related complications were compared by genotype, adjusting for age, sex, body mass index (BMI), current smoking and menopausal status. RESULTS: In total, 266 of the 306 patients (87%) were homozygous for C282Y, and 40 (13%) were compound heterozygous. The 2 groups did not differ by median age [60 (interquartile range [IQR] 53 to 68) vs. 61 (55 to 67) years, P=0.8], sex (female: 48.8% vs. 37.5%, P=0.18) or current smoking habits (12.4% vs. 10%, P=0.3). As compared with compound heterozygous patients, C282Y homozygous patients had higher median serum ferritin concentration at diagnosis [1090 (IQR 610 to 2210) vs. 603 (362 to 950) µg/L, P<0.001], higher median transferrin saturation [80% (IQR 66 to 91%) vs. 63% (55 to 72%), P<0.001]) and lower median BMI [24.8 (22.1 to 26.9) vs. 26.2 (23.5 to 30.3) kg/m2, P<0.003]. The overall prevalence of self-reported OA was significantly higher with C282Y homozygosity than compound heterozygosity (53.4% vs. 32.5%; adjusted odds ratio [aOR] 2.4 [95% confidence interval 1.2-5.0]), as was self-reported OP (25.6% vs. 7.5%; aOR 3.5 [1.1-12.1]). CONCLUSION: Patients with C282Y homozygosity may be at increased risk of musculoskeletal complications of HH.

Keeping it natural: Does persuasive magazine content have an effect on young women's intentions for birth?

Information in the popular media tends to be biased toward promoting the benefits of medicalized birth for low-risk pregnancies. We aimed to assess the effect of communicating the benefits of non-medicalized birth in magazine articles on women’s birth intentions and to identify the mechanisms by which social communication messages affected women’s intentions for birth. A convenience sample of 180 nulliparous Australian women aged 18–35 years were randomly exposed to a magazine article endorsing non-medicalized birth (using either celebrity or non-celebrity endorsement) or organic eating (control) throughout June–July 2011. Magazine articles that endorsed non-medicalized birth targeted perceived risk of birth, expectations for labor and birth, and attitudes toward birth. These variables and intention for birth were assessed by self-report before and after exposure. Exposure to a magazine article that endorsed non-medicalized birth significantly reduced women’s intentions for a medicalized birth, regardless of whether the endorsement was by celebrities or non-celebrities. Changes in perceived risk of birth mediated the effect of magazine article exposure on women’s intentions for a medicalized birth. Persuasive communication that endorses non-medicalized birth could be delivered at the population level and may reduce women’s intentions for a medicalized birth.

Dietary fat manipulation has a greater impact on postprandial lipid metabolism than the apolipoprotein E (epsilon) genotype: insights from the SATgenε study

Scope: Our aim was to determine the effects of chronic dietary fat manipulation on postprandial lipaemia according to apolipoprotein (APO)E genotype. Methods and results:Men (mean age 53 (SD 9) years), prospectively recruited for the APOE genotype (n = 12 E3/E3, n = 11 E3/E4), were assigned to a low fat (LF), high fat, high-saturated fat (HSF), and HSF diet with 3.45 g/day docosahexaenoic acid (HSF-DHA), each for an 8-week period in the same order. At the end of each dietary period, a postprandial assessment was performed using a test meal with a macronutrient profile representative of that dietary intervention. A variable postprandial plasma triacylglycerol (TAG) response according to APOE genotype was evident, with a greater sensitivity to the TAG-lowering effects of DHA in APOE4 carriers (p ≤ 0.005). There was a lack of an independent genotype effect on any of the lipid measures. In the groups combined, dietary fat manipulation had a significant impact on lipids in plasma and Svedberg flotation rate (Sf) 60–400 TAG-rich lipoprotein fraction, with lower responses following the HSF-DHA than HSF intervention (p < 0.05). Conclusion: Although a modest impact of APOE genotype was observed on the plasma TAG profile, dietary fat manipulation emerged as a greater modulator of the postprandial lipid response in normolipidaemic men.

The peripheral L-arginine-nitric oxide-cyclic GMP pathway and ATP-sensitive K+ channels are involved in the antinociceptive effect of crotalphine on neuropathic pain in rats

Crotalphine, a 14 amino acid peptide first isolated from the venom of the South American rattlesnake Crotalus durissus terrificus, induces a peripheral long-lasting and opioid receptor-mediated antinociceptive effect in a rat model of neuropathic pain induced by chronic constriction of the sciatic nerve. In the present study, we further characterized the molecular mechanisms involved in this effect, determining the type of opioid receptor responsible for this effect and the involvement of the nitric oxide-cyclic GMP pathway and of K+ channels. Crotalphine (0.2 or 5 mu g/kg, orally; 0.0006 mu g/paw), administered on day 14 after nerve constriction, inhibited mechanical hyperalgesia and low-threshold mechanical allodynia. The effect of the peptide was antagonized by intraplantar administration of naltrindole, an antagonist of delta-opioid receptors, and partially reversed by norbinaltorphimine, an antagonist of kappa-opioid receptors. The effect of crotalphine was also blocked by 7-nitroindazole, an inhibitor of the neuronal nitric oxide synthase; by 1H-(1,2,4) oxadiazolo[4,3-a]quinoxaline-1-one, an inhibitor of guanylate cyclase activation; and by glibenclamide, an ATP-sensitive K+ channel blocker. The results suggest that peripheral delta-opioid and kappa-opioid receptors, the nitric oxide-cyclic GMP pathway, and ATP-sensitive K+ channels are involved in the antinociceptive effect of crotalphine. The present data point to the therapeutic potential of this peptide for the treatment of chronic neuropathic pain. Behavioural Pharmacology 23:14-24 (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Patterns

In recent years there has been widespread interest in patterns, perhaps provoked by a realisation that they constitute a fundamental brain activity and underpin many artificial intelligence systems. Theorised concepts of spatial patterns including scale, proportion, and symmetry, as well as social and psychological understandings are being revived through digital/parametric means of visualisation and production. The effect of pattern as an ornamental device has also changed from applied styling to mediated dynamic effect. The interior has also seen patterned motifs applied to wall coverings, linen, furniture and artefacts with the effect of enhancing aesthetic appreciation, or in some cases causing psychological and/or perceptual distress (Rodemann 1999). ----- ----- While much of this work concerns a repeating array of surface treatment, Philip Ball’s The Self- Made Tapestry: Pattern Formation in Nature (1999) suggests a number of ways that patterns are present at the macro and micro level, both in their formation and disposition. Unlike the conventional notion of a pattern being the regular repetition of a motif (geometrical or pictorial) he suggests that in nature they are not necessarily restricted to a repeating array of identical units, but also include those that are similar rather than identical (Ball 1999, 9). From his observations Ball argues that they need not necessarily all be the same size, but do share similar features that we recognise as typical. Examples include self-organized patterns on a grand scale such as sand dunes, or fractal networks caused by rivers on hills and mountains, through to patterns of flow observed in both scientific experiments and the drawings of Leonardo da Vinci.

Determinants of skin self-examination (SSE) in men aged 50 years or older

Background: Queensland men aged 50 years and older are at high risk for melanoma. Early detection via skin self examination (SSE) (particularly whole-body SSE) followed by presentation to a doctor with suspicious lesions, may decrease morbidity and mortality from melanoma. Prevalence of whole-body SSE (wbSSE) is lower in Queensland older men compared to other population subgroups. With the exception of the present study no previous research has investigated the determinants of wbSSE in older men, or interventions to increase the behaviour in this population. Furthermore, although past SSE intervention studies for other populations have cited health behaviour models in the development of interventions, no study has tested these models in full. The Skin Awareness Study: A recent randomised trial, called the Skin Awareness Study, tested the impact of a video-delivered intervention compared to written materials alone on wbSSE in men aged 50 years or older (n=930). Men were recruited from the general population and interviewed over the telephone at baseline and 13 months. The proportion of men who reported wbSSE rose from 10% to 31% in the control group, and from 11% to 36% in the intervention group. Current research: The current research was a secondary analysis of data collected for the Skin Awareness Study. The objectives were as follows: • To describe how men who did not take up any SSE during the study period differed from those who did take up examining their skin. • To determine whether the intervention program was successful in affecting the constructs of the Health Belief Model it was aimed at (self-efficacy, perceived threat, and outcome expectations); and whether this in turn influenced wbSSE. • To determine whether the Health Action Process Approach (HAPA) was a better predictor of wbSSE behaviour compared to the Health Belief Model (HBM). Methods: For objective 1, men who did not report any past SSE at baseline (n=308) were categorised as having ‘taken up SSE’ (reported SSE at study end) or ‘resisted SSE’ (reported no SSE at study end). Bivariate logistic regression, followed by multivariable regression, investigated the association between participant characteristics measured at baseline and resisting SSE. For objective 2 proxy measures of self-efficacy, perceived threat, and outcome expectations were selected. To determine whether these mediated the effect of the intervention on the outcome, a mediator analysis was performed with all participants who completed interviews at both time points (n=830) following the Baron and Kenny approach, modified for use with structural equation modelling (SEM). For objective 3, control group participants only were included (n=410). Proxy measures of all HBM and HAPA constructs were selected and SEM was used to build up models and test the significance of each hypothesised pathway. A likelihood ratio test compared the HAPA to the HBM. Results: Amongst men who did not report any SSE at baseline, 27% did not take up any SSE by the end of the study. In multivariable analyses, resisting SSE was associated with having more freckly skin (p=0.027); being unsure about the statement ‘if I saw something suspicious on my skin, I’d go to the doctor straight away’ (p=0.028); not intending to perform SSE (p=0.015), having lower SSE self-efficacy (p<0.001), and having no recommendation for SSE from a doctor (p=0.002). In the mediator analysis none of the tested variables mediated the relationship between the intervention and wbSSE. In regards to health behaviour models, the HBM did not predict wbSSE well overall. Only the construct of self-efficacy was a significant predictor of future wbSSE (p=0.001), while neither perceived threat (p=0.584) nor outcome expectations (p=0.220) were. By contrast, when the HAPA constructs were added, all three HBM variables predicted intention to perform SSE, which in turn predicted future behaviour (p=0.015). The HAPA construct of volitional self-efficacy was also associated with wbSSE (p=0.046). The HAPA was a significantly better model compared to the HBM (p<0.001). Limitations: Items selected to measure HBM and HAPA model constructs for objectives 2 and 3 may not have accurately reflected each construct. Conclusions: This research added to the evidence base on how best to target interventions to older men; and on the appropriateness of particular health behaviour models to guide interventions. Findings indicate that to overcome resistance those men with more negative pre-existing attitudes to SSE (not intending to do it, lower initial self-efficacy) may need to be targeted with more intensive interventions in the future. Involving general practitioners in recommending SSE to their patients in this population, alongside disseminating an intervention, may increase its success. Comparison of the HBM and HAPA showed that while two of the three HBM variables examined did not directly predict future wbSSE, all three were associated with intention to self-examine skin. This suggests that in this population, intervening on these variables may increase intention to examine skin, but not necessarily the behaviour itself. Future interventions could potentially focus on increasing both the motivational variables of perceived threat and outcome expectations as well as a combination of both action and volitional self-efficacy; with the aim of increasing intention as well as its translation to taking up and maintaining regular wbSSE.

The relationship between chronic disease self-efficacy and nutritional status, functional ability and quality of life in older adults at risk of hospital readmission

Background and significance: Older adults with chronic diseases are at increasing risk of hospital admission and readmission. Approximately 75% of adults have at least one chronic condition, and the odds of developing a chronic condition increases with age. Chronic diseases consume about 70% of the total Australian health expenditure, and about 59% of hospital events for chronic conditions are potentially preventable. These figures have brought to light the importance of the management of chronic disease among the growing older population. Many studies have endeavoured to develop effective chronic disease management programs by applying social cognitive theory. However, limited studies have focused on chronic disease self-management in older adults at high risk of hospital readmission. Moreover, although the majority of studies have covered wide and valuable outcome measures, there is scant evidence on examining the fundamental health outcomes such as nutritional status, functional status and health-related quality of life. Aim: The aim of this research was to test social cognitive theory in relation to self-efficacy in managing chronic disease and three health outcomes, namely nutritional status, functional status, and health-related quality of life, in older adults at high risk of hospital readmission. Methods: A cross-sectional study design was employed for this research. Three studies were undertaken. Study One examined the nutritional status and validation of a nutritional screening tool; Study Two explored the relationships between participants. characteristics, self-efficacy beliefs, and health outcomes based on the study.s hypothesized model; Study Three tested a theoretical model based on social cognitive theory, which examines potential mechanisms of the mediation effects of social support and self-efficacy beliefs. One hundred and fifty-seven patients aged 65 years and older with a medical admission and at least one risk factor for readmission were recruited. Data were collected from medical records on demographics, medical history, and from self-report questionnaires. The nutrition data were collected by two registered nurses. For Study One, a contingency table and the kappa statistic was used to determine the validity of the Malnutrition Screening Tool. In Study Two, standard multiple regression, hierarchical multiple regression and logistic regression were undertaken to determine the significant influential predictors for the three health outcome measures. For Study Three, a structural equation modelling approach was taken to test the hypothesized self-efficacy model. Results: The findings of Study One suggested that a high prevalence of malnutrition continues to be a concern in older adults as the prevalence of malnutrition was 20.6% according to the Subjective Global Assessment. Additionally, the findings confirmed that the Malnutrition Screening Tool is a valid nutritional screening tool for hospitalized older adults at risk of readmission when compared to the Subjective Global Assessment with high sensitivity (94%), and specificity (89%) and substantial agreement between these two methods (k = .74, p < .001; 95% CI .62-.86). Analysis data for Study Two found that depressive symptoms and perceived social support were the two strongest influential factors for self-efficacy in managing chronic disease in a hierarchical multiple regression. Results of multivariable regression models suggested advancing age, depressive symptoms and less tangible support were three important predictors for malnutrition. In terms of functional status, a standard regression model found that social support was the strongest predictor for the Instrumental Activities of Daily Living, followed by self-efficacy in managing chronic disease. The results of standard multiple regression revealed that the number of hospital readmission risk factors adversely affected the physical component score, while depressive symptoms and self-efficacy beliefs were two significant predictors for the mental component score. In Study Three, the results of the structural equation modelling found that self-efficacy partially mediated the effect of health characteristics and depression on health-related quality of life. The health characteristics had strong direct effects on functional status and body mass index. The results also indicated that social support partially mediated the relationship between health characteristics and functional status. With regard to the joint effects of social support and self-efficacy, social support fully mediated the effect of health characteristics on self-efficacy, and self-efficacy partially mediated the effect of social support on functional status and health-related quality of life. The results also demonstrated that the models fitted the data well with relative high variance explained by the models, implying the hypothesized constructs under discussion were highly relevant, and hence the application for social cognitive theory in this context was supported. Conclusion: This thesis highlights the applicability of social cognitive theory on chronic disease self-management in older adults at risk of hospital readmission. Further studies are recommended to validate and continue to extend the development of social cognitive theory on chronic disease self-management in older adults to improve their nutritional and functional status, and health-related quality of life.

The relationship between cannabis outcome expectancies and cannabis refusal self-efficacy in a treatment population

Background and aims Self-efficacy beliefs and outcome expectancies are central to Social Cognitive Theory (SCT). Alcohol studies demonstrate the theoretical and clinical utility of applying both SCT constructs. This study examined the relationship between refusal self-efficacy and outcome expectancies in a sample of cannabis users, and tested formal mediational models. Design Patients referred for cannabis treatment completed a comprehensive clinical assessment, including recently validated cannabis expectancy and refusal self-efficacy scales. Setting A hospital alcohol and drug out-patient clinic. Participants Patients referred for a cannabis treatment [n = 1115, mean age 26.29, standard deviation (SD) 9.39]. Measurements The Cannabis Expectancy Questionnaire (CEQ) and Cannabis Refusal Self-Efficacy Questionnaire (CRSEQ) were completed, along with measures of cannabis severity [Severity of Dependence Scale (SDS)] and cannabis consumption. Findings Positive (β = −0.29, P < 0.001) and negative (β = −0.19, P < 0.001) cannabis outcome expectancies were associated significantly with refusal self-efficacy. Refusal self-efficacy, in turn, fully mediated the association between negative expectancy and weekly consumption [95% confidence interval (CI) = 0.03, 0.17] and partially mediated the effect of positive expectancy on weekly consumption (95% CI = 0.06, 0.17). Conclusions Consistent with Social Cognitive Theory, refusal self-efficacy (a person's belief that he or she can abstain from cannabis use) mediates part of the association between cannabis outcome expectancies (perceived consequences of cannabis use) and cannabis use.

Young people's uses of music for well-being

The period between 15 and 25 years is characterised by much personal change and is the peak age of onset of mental health problems. This prompts an interest in everyday strategies that young people might use to support their well-being. Music use is the preferred leisure activity among young people yet little is known about how music is linked to well-being in this population. This study aimed to develop and test a model of the relationships between young people’s use of music and their well-being, drawing on theories from the music psychology and clinical psychology fields. A qualitative analysis of transcripts from focus groups with 11 participants aged 15–25 years revealed four ways in which music listening links with well-being: relationship building, modifying emotions, modifying cognitions and emotional immersion. These linking variables were operationalised using questionnaire scores and tested on a new sample of 107 young people. Results of a multiple mediation analysis revealed that music listening was significantly related to all four linking variables, but not directly related to well-being as measured by the Mental Health Continuum. Nevertheless, the four linking variables indirectly mediated the effect of music listening on social wellbeing. The findings are consistent with earlier research on the role of music in emotion regulation and social connection although there are clearly other factors involved in determining young peoples’ well-being. These findings will help inform music-based interventions for young people.

An empirical analysis of the factors and measures of Enterprise Architecture Management success

Enterprise Architecture Management (EAM) is discussed in academia and industry as a vehicle to guide IT implementations, alignment, compliance assessment, or technology management. Still, a lack of knowledge prevails about how EAM can be successfully used, and how positive impact can be realized from EAM. To determine these factors, we identify EAM success factors and measures through literature reviews and exploratory interviews and propose a theoretical model that explains key factors and measures of EAM success. We test our model with data collected from a cross-sectional survey of 133 EAM practitioners. The results confirm the existence of an impact of four distinct EAM success factors, ‘EAM product quality’, ‘EAM infrastructure quality’, ‘EAM service delivery quality’, and ‘EAM organizational anchoring’, and two important EAM success measures, ‘intentions to use EAM’ and ‘Organizational and Project Benefits’ in a confirmatory analysis of the model. We found the construct ‘EAM organizational anchoring’ to be a core focal concept that mediated the effect of success factors such as ‘EAM infrastructure quality’ and ‘EAM service quality’ on the success measures. We also found that ‘EAM satisfaction’ was irrelevant to determining or measuring success. We discuss implications for theory and EAM practice.

Follicle stimulating hormone secretion and dominant follicle growth during treatment of Bos indicus heifers with intra-vaginal progesterone releasing devices, oestradiol benzoate, equine chorionic gonadotrophin and prostaglandin F-2 alpha

The aim of this study was to investigate the effects on follicle stimulating hormone (FSH) secretion and dominant follicle (OF) growth, of treatment of Bos indicus heifers with different combinations of intra-vaginal progesterone releasing devices (IPRD), oestradiol benzoate (ODB), PGF(2 alpha), and eCG. Two-year-old Brahman (BN; n=30) and Brahman-cross (BNX; n=34) heifers were randomly allocated to three IPRD-treatments: (i) standard-dose IPRD [CM 1.56 g; 1.56 g progesterone (P-4); n = 17]; (ii) half-dose IPRD (CM 0.78 g; 0.78 g p(4); n=15); (iii) half-dose IPRD + 300 IU eCG at IPRD removal (CM 0.78 g+G; n=14); and, (iv) non-IPRD control (2 x PGF(2 alpha); n=18) 500 mu g cloprostenol on Days -16 and -2. IPRD-treated heifers received 250 mu g PGF(2 alpha) at IPRD insertion (Day 10) and IPRD removal (Day -2) and 1 mg ODB on Day -10 and Day -1. Follicular dynamics were monitored daily by trans-rectal ultrasonography from Day -10 to Day 1. Blood samples for determination of P-4 were collected daily and samples for FSH determination were collected at 12 h intervals from Day -9 to Day -2. A significant surge in concentrations of FSH was observed in the 2 x PGF(2 alpha), treatment 12 h prior and 48 h after follicular wave emergence, but not in the IPRD-treated heifers. Estimated mean concentrations of total plasma P-4 during the 8 days of IPRD insertion was greater (P<0.001) in the CM 1.56 g P-4 treated heifers compared to the CM 0.78 g P-4 treated heifers (18.38 ng/ml compared with 11.09 ng/ml, respectively). A treatment by genotype interaction (P=0.036) was observed in the mean plasma P4 concentration in heifers with no CL during IPRD insertion, whereby BN heifers in the CM 1.56 g treatment had greater plasma P-4 than the BNX heifers on Days-9, -7, -6, -5, and -4. However, there was no genotype effect in the CM 0.78 g +/- G or the 2 x PGF(2 alpha) treatment. Treatment had no effect on the DF growth from either day of wave emergence (P=0.378) or day of IPRD removal (P=0.780) to ovulation. This study demonstrates that FSH secretion in B. indicus heifers treated with a combination of IPRD's and ODB to synchronise ovulation was suppressed during the period of IPRD insertion but no significant effect on growth of the DF was observed. (C) 2013 Elsevier B.V. All rights reserved.

Cross-hemispheric collaboration and segregation associated with task difficulty as revealed by structural and functional connectivity.

Although it is known that brain regions in one hemisphere may interact very closely with their corresponding contralateral regions (collaboration) or operate relatively independent of them (segregation), the specific brain regions (where) and conditions (how) associated with collaboration or segregation are largely unknown. We investigated these issues using a split field-matching task in which participants matched the meaning of words or the visual features of faces presented to the same (unilateral) or to different (bilateral) visual fields. Matching difficulty was manipulated by varying the semantic similarity of words or the visual similarity of faces. We assessed the white matter using the fractional anisotropy (FA) measure provided by diffusion tensor imaging (DTI) and cross-hemispheric communication in terms of fMRI-based connectivity between homotopic pairs of cortical regions. For both perceptual and semantic matching, bilateral trials became faster than unilateral trials as difficulty increased (bilateral processing advantage, BPA). The study yielded three novel findings. First, whereas FA in anterior corpus callosum (genu) correlated with word-matching BPA, FA in posterior corpus callosum (splenium-occipital) correlated with face-matching BPA. Second, as matching difficulty intensified, cross-hemispheric functional connectivity (CFC) increased in domain-general frontopolar cortex (for both word and face matching) but decreased in domain-specific ventral temporal lobe regions (temporal pole for word matching and fusiform gyrus for face matching). Last, a mediation analysis linking DTI and fMRI data showed that CFC mediated the effect of callosal FA on BPA. These findings clarify the mechanisms by which the hemispheres interact to perform complex cognitive tasks.