Comparison between Suitable Priors for Additive Bayesian Networks

Additive Bayesian networks are types of graphical models that extend the usual Bayesian generalized linear model to multiple dependent variables through the factorisation of the joint probability distribution of the underlying variables. When fitting an ABN model, the choice of the prior of the parameters is of crucial importance. If an inadequate prior - like a too weakly informative one - is used, data separation and data sparsity lead to issues in the model selection process. In this work a simulation study between two weakly and a strongly informative priors is presented. As weakly informative prior we use a zero mean Gaussian prior with a large variance, currently implemented in the R-package abn. The second prior belongs to the Student's t-distribution, specifically designed for logistic regressions and, finally, the strongly informative prior is again Gaussian with mean equal to true parameter value and a small variance. We compare the impact of these priors on the accuracy of the learned additive Bayesian network in function of different parameters. We create a simulation study to illustrate Lindley's paradox based on the prior choice. We then conclude by highlighting the good performance of the informative Student's t-prior and the limited impact of the Lindley's paradox. Finally, suggestions for further developments are provided.Comment: 8 pages, 4 figure

Use of simple sequence repeat (SSR) markers for screening blue disease resistance in cotton germplasm exchange

Blue disease of cotton is an economically important disease of the crop first described from the Central African Republic and spread to other countries. Brazil and other South American countries record crop losses of up to 80% from infection but no cases of the disease have been reported in Tanzania. Resistance to the disease has been found in African germplasm and transferred to crop cultivars worldwide. Molecular markers linked to blue disease resistance genes have been identified presenting useful tools to identify resistant germplasm. All plants of three Tanzanian cotton cultivars (Gossypium hirsutum L.) UK91, UK08 and UKM08 showed resistance alleles for both the simple sequence repeat (SSR) (DC20027-202 bp) and single nucleotide polymorphisms (SNP) (NG0204310-C) markers but some plants of the Brazilian cultivars (G. hirsutum L.); Ipê, Cedro, Aroeira and Araça lacked resistance alleles. The findings suggest the need for caution to be taken during introduction of exotic germplasm and recognize the value of resistance trait to susceptible Brazilian germplasm when  breeding for blue disease resistance.Key words: Cotton blue disease, cotton single nucleotide polymorphisms (SNPs), simple sequence repeat(SSR), resistant alleles in cotton

Marker-assisted Screening of Cotton Cultivars for Bacterial Blight Resistance Gene

Bacterial blight or leaf blight is a common disease of cotton in almost all cotton growing countries, including Tanzania. Bacterial blight is caused by infection of plants with the bacteria (Xanthomonas axonopodis pv. malvacearum) and the use of resistant cultivars is the most effective long-term strategy to manage the disease. The strategy starts with identification of resistant individuals, which can be identified either phenotypically by inoculation or by use of molecular markers linked to genes that confer resistance. The B12 gene is known to confer a high level of resistance to all Xanthomonas axonopodis pv. malvacearum races found in USA and Africa. Four Brazilian and three local cultivars were screened for the presence of SSR (CIR246) and SNP NG0207155 markers linked to B12. The SNP marker showed the greatest frequency of resistance-linked alleles in the cultivar UK08 (85.71%) followed by UK91 (75%),UKM08 and Ipê (25%), Araça(8.33%),Aroeira (7.1%) and the least in Cedro (0%). Comparable results were recorded for SSR marker where the cultivar UK08 presented relatively higher frequency of resistance alleles (85.71%) of samples tested followed by UK91 (68.75%), UKM08 (25%), Ipê, Aroeira and Araça (8%) and the last was Cedro (0%). The results suggest the potential utility of Tanzanian germplasm in breeding for resistance to Xanthomonas axonopodis pv. malvacearum race 18 and the need to purify the same germplasm by marker assisted selection.Key words: Bacterial Blight, Cotton, Resistant cultivars, Tanzania

Reliability and validity of the Turkish translation of the beliefs about medicines questionnaire (BMQ-T) in patients with Behçet’s disease

OBJECTIVES: The aim of this study was to evaluate the reliability and validity of the Turkish translation of the Beliefs about Medicines Questionnaire (BMQ-T, ©Prof. Rob Horne) for patients with Behçet's disease. METHODS: This methodological study enrolled a sample of 125 patients. The scale was adapted to Turkish through a process including translation, comparison with versions in other languages, back translation, and pretesting. Construct validity was evaluated by factor analysis. Medication adherence evaluated as poor, moderate and good according to the Morisky Medication Adherence Scale (MMAS). BMQ-T scores compared along medication adherence status groups. RESULTS: In our study, as in the original scale, the factor analysis confirmed that the BMQ-T had a four-factor structure explaining 54.73% of the total variance. The BMQ-T had acceptable internal consistency (Cronbach's alpha coefficient: Specific Necessity=.812; Specific Concerns=.672; General Harm=.677; General Overuse=.656), adequate test-retest reliability (intraclass correlation coefficients: Specific Necessity=.715; Specific Concerns=.680; General Harm=.678; General Overuse=.327). Specific Necessity and Specific Concerns scores were significantly different between medication adherence status groups. CONCLUSIONS: The psychometric properties of the BMQ-T were consistent with those reported in the original study. The BMQ-T was found to be a valid and reliable tool for evaluating beliefs about medicines in patients with Behçet's disease

Meropenem vs standard of care for treatment of neonatal late onset sepsis (NeoMero1): A randomised controlled trial.

BACKGROUND: The early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, recruited in single centres or countries, evaluated antibiotics not in clinical use anymore and had variable inclusion/exclusion criteria and outcome measures. Moreover, antibiotic-resistant bacteria have become a major problem in many countries worldwide. We hypothesized that efficacy of meropenem as a broad-spectrum antibiotic is superior to standard of care regimens (SOC) in empiric treatment of LOS and aimed to compare meropenem to SOC in infants aged 44 weeks meeting the Goldstein criteria of sepsis, were randomized in a 1:1 ratio to receive meropenem or one of the two SOC regimens (ampicillin+gentamicin or cefotaxime+gentamicin) chosen by each site prior to the start of the study for 8-14 days. The primary outcome was treatment success (survival, no modification of allocated therapy, resolution/improvement of clinical and laboratory markers, no need of additional antibiotics and presumed/confirmed eradication of pathogens) at test-of-cure visit (TOC) in full analysis set. Stool samples were tested at baseline and Day 28 for meropenem-resistant Gram-negative organisms (CRGNO). The primary analysis was performed in all randomised patients and in patients with culture confirmed LOS. Proportions of participants with successful outcome were compared by using a logistic regression model adjusted for the stratification factors. From September 3, 2012 to November 30th 2014, total of 136 patients (instead of planned 275) in each arm were randomized; 140 (52%) were culture positive. Successful outcome at TOC was achieved in 44/136 (32%) in the meropenem arm vs. 31/135 (23%) in the SOC arm (p = 0.087). The respective numbers in patients with positive cultures were 17/63 (27%) vs. 10/77 (13%) (p = 0.022). The main reason of failure was modification of allocated therapy. Treatment emergent adverse events occurred in 72% and serious adverse events in 17% of patients, the Day 28 mortality was 6%. Cumulative acquisition of CRGNO by Day 28 occurred in 4% of patients in the meropenem and 12% in the SOC arm (p = 0.052). CONCLUSIONS: Within this study population, we found no evidence that meropenem was superior to SOC in terms of success at TOC, short term hearing disturbances, safety or mortality were similar in both treatment arms but the study was underpowered to detect the planned effect. Meropenem treatment did not select for colonization with CRGNOs. We suggest that meropenem as broad-spectrum antibiotic should be reserved for neonates who are more likely to have Gram-negative LOS, especially in NICUs where microorganisms producing extended spectrum- and AmpC type beta-lactamases are circulating

Effects of hyperoxia on 18F-fluoro-misonidazole brain uptake and tissue oxygen tension following middle cerebral artery occlusion in rodents: Pilot studies.

PURPOSE: Mapping brain hypoxia is a major goal for stroke diagnosis, pathophysiology and treatment monitoring. 18F-fluoro-misonidazole (FMISO) positron emission tomography (PET) is the gold standard hypoxia imaging method. Normobaric hyperoxia (NBO) is a promising therapy in acute stroke. In this pilot study, we tested the straightforward hypothesis that NBO would markedly reduce FMISO uptake in ischemic brain in Wistar and spontaneously hypertensive rats (SHRs), two rat strains with distinct vulnerability to brain ischemia, mimicking clinical heterogeneity. METHODS: Thirteen adult male rats were randomized to distal middle cerebral artery occlusion under either 30% O2 or 100% O2. FMISO was administered intravenously and PET data acquired dynamically for 3hrs, after which magnetic resonance imaging (MRI) and tetrazolium chloride (TTC) staining were carried out to map the ischemic lesion. Both FMISO tissue uptake at 2-3hrs and FMISO kinetic rate constants, determined based on previously published kinetic modelling, were obtained for the hypoxic area. In a separate group (n = 9), tissue oxygen partial pressure (PtO2) was measured in the ischemic tissue during both control and NBO conditions. RESULTS: As expected, the FMISO PET, MRI and TTC lesion volumes were much larger in SHRs than Wistar rats in both the control and NBO conditions. NBO did not appear to substantially reduce FMISO lesion size, nor affect the FMISO kinetic rate constants in either strain. Likewise, MRI and TTC lesion volumes were unaffected. The parallel study showed the expected increases in ischemic cortex PtO2 under NBO, although these were small in some SHRs with very low baseline PtO2. CONCLUSIONS: Despite small samples, the apparent lack of marked effects of NBO on FMISO uptake suggests that in permanent ischemia the cellular mechanisms underlying FMISO trapping in hypoxic cells may be disjointed from PtO2. Better understanding of FMISO trapping processes will be important for future applications of FMISO imaging

Brain hypoxia mapping in acute stroke: Back-to-back T2′ MR versus 18F-fluoromisonidazole PET in rodents

Background Mapping the hypoxic brain in acute ischemic stroke has considerable potential for both diagnosis and treatment monitoring. PET using (18)F-fluoro-misonidazole (FMISO) is the reference method; however, it lacks clinical accessibility and involves radiation exposure. MR-based T2' mapping may identify tissue hypoxia and holds clinical potential. However, its validation against FMISO imaging is lacking. Here we implemented back-to-back FMISO-PET and T2' MR in rodents subjected to acute middle cerebral artery occlusion. For direct clinical relevance, regions of interest delineating reduced T2' signal areas were manually drawn. Methods Wistar rats were subjected to filament middle cerebral artery occlusion, immediately followed by intravenous FMISO injection. Multi-echo T2 and T2* sequences were acquired twice during FMISO brain uptake, interleaved with diffusion-weighted imaging. Perfusion-weighted MR was also acquired whenever feasible. Immediately following MR, PET data reflecting the history of FMISO brain uptake during MR acquisition were acquired. T2' maps were generated voxel-wise from T2 and T2*. Two raters independently drew T2' lesion regions of interest. FMISO uptake and perfusion data were obtained within T2' consensus regions of interest, and their overlap with the automatically generated FMISO lesion and apparent diffusion coefficient lesion regions of interest was computed. Results As predicted, consensus T2' lesion regions of interest exhibited high FMISO uptake as well as substantial overlap with the FMISO lesion and significant hypoperfusion, but only small overlap with the apparent diffusion coefficient lesion. Overlap of the T2' lesion regions of interest between the two raters was ∼50%. Conclusions This study provides formal validation of T2' to map non-core hypoxic tissue in acute stroke. T2' lesion delineation reproducibility was suboptimal, reflecting unclear lesion borders.This study was funded by an EU Grant (EUSTROKE Health-F2-2008-2022131). DJW was funded by an MRC collaborative grant (G0600986), RM by the NIHR Cambridge Biomedical Research Centre, and UJK by a fellowship from the Deutsche Forschungsgemeinschaft (Je 598/1-1)

Understanding the power of the prime minister : structure and agency in models of prime ministerial power

Understanding the power of the prime minister is important because of the centrality of the prime minister within the core executive of British government, but existing models of prime ministerial power are unsatisfactory for various reasons. This article makes an original contribution by providing an overview and critique of the dominant models of prime ministerial power, highlighting their largely positivist bent and the related problem of the prevalence of overly parsimonious conceptions of the structural contexts prime ministers face. The central argument the paper makes is that much of the existing literature on prime ministerial power is premised on flawed understandings of the relationship between structure and agency, that this leads to misunderstandings of the real scope of prime ministerial agency, as well as its determinants, and that this can be rectified by adopting a strategic-relational view of structure and agency