A Bayesian model for classifying all differentially expressed proteins simultaneously in 2D PAGE gels

Background: Two-dimensional polyacrylamide gel electrophoresis (2D PAGE) is commonly used to identify differentially expressed proteins under two or more experimental or observational conditions. Wu et al (2009) developed a univariate probabilistic model which was used to identify differential expression between Case and Control groups, by applying a Likelihood Ratio Test (LRT) to each protein on a 2D PAGE. In contrast to commonly used statistical approaches, this model takes into account the two possible causes of missing values in 2D PAGE: either (1) the non-expression of a protein; or (2) a level of expression that falls below the limit of detection.Results: We develop a global Bayesian model which extends the previously described model. Unlike the univariate approach, the model reported here is able treat all differentially expressed proteins simultaneously. Whereas each protein is modelled by the univariate likelihood function previously described, several global distributions are used to model the underlying relationship between the parameters associated with individual proteins. These global distributions are able to combine information from each protein to give more accurate estimates of the true parameters. In our implementation of the procedure, all parameters are recovered by Markov chain Monte Carlo (MCMC) integration. The 95% highest posterior density (HPD) intervals for the marginal posterior distributions are used to determine whether differences in protein expression are due to differences in mean expression intensities, and/or differences in the probabilities of expression.Conclusions: Simulation analyses showed that the global model is able to accurately recover the underlying global distributions, and identify more differentially expressed proteins than the simple application of a LRT. Additionally, simulations also indicate that the probability of incorrectly identifying a protein as differentially expressed (i.e., the False Discovery Rate) is very low. The source code is available at https://github.com/stevenhwu/BIDE-2D

Outcome of pregnancy after the mustard operation for transposition of the great arteries with intact ventricular septum

AbstractObjectives. This study examined the outcome of pregnancy in patients with transposition of the great arteries and an intact ventricular septum after a Mustard operation.Background. Before the introduction of surgical treatment, most children with transposition of the great arteries died in early infancy. A number of these patients have now reached their reproductive years. There is little information about the effect of pregnancy on cardiovascular status, particularly the ability of the right ventricle to adjust to the hemodynamic changes of pregnancy. The outcome for the offspring and their risk of congenital heart disease are also unknown.Methods. Twenty-three female late survivors after the Mustard operation >15 years of age were reviewed in relation to the occurrence of pregnancy and its outcome. Serial echocardiographic estimates of right ventricular volume during pregnancy were made in three local patients.Results. Nine women had 15 pregnancies. They were asymptomatic before pregnancy and remained free from cardiac symptoms during each pregnancy. Right ventricular volume in the three patients studied increased during pregnancy but returned to normal at 8 to 11 weeks postpartum. There were 12 live births, 2 spontaneous abortions and 1 intrauterine death. None of the liveborn infants had evidence of congenital heart disease.Conclusions. In this small group of women with good quality late survival after a Mustard operation, pregnancy was well tolerated. We suspect that the incidence of congenital heart disease in infants of mothers with transposition of the great arteries will be at the lower end of the range for mothers with different types of congenital heart disease, but further data will be needed to confirm this

A Prospective Cohort Study Investigating Associations between Hyperemesis Gravidarum and Cognitive, Behavioural and Emotional Well-Being in Pregnancy

Objectives: To investigate the association between hyperemesis gravidarum and altered cognitive, behavioural and emotional well-being in pregnancy. Methods: The study cohort consisted of 3423 nulliparous women recruited in the Screening for Pregnancy Endpoints (SCOPE) study performed in Auckland, New Zealand; Adelaide, Australia; Cork, Ireland; Manchester and London, United Kingdom between November 2004 and August 2008. Women were interviewed at 15±1 weeks' gestation and at 20±1weeks' gestation. Women with a diagnosis of hyperemesis gravidarum (HG) were compared with women who did not have a diagnosis of HG. Main outcome measures included the Short form State- Trait Anxiety Inventory (STAI) score (range 6–24), Perceived Stress Scale score (PSS, range 0–30), Edinburgh Postnatal Depression Scale (EPDS) score (range 0–30 or categories a–c) and behavioural responses to pregnancy score (limiting/resting [range 0–20] and all-or-nothing [range 0–28]). Results: During the study period 164 women suffered from HG prior to their 15 week interview. Women with HG had significantly higher mean STAI, PSS, EPDS and limiting response to pregnancy scores compared to women without HG. These differences were observed at both 15±1 and 20±1 weeks' of gestation. The magnitude of these differences was greater in women with severe HG compared to all women with HG. Women with severe HG had an increased risk of having a spontaneous preterm birth compared with women without HG (adjusted OR 2.6 [95% C.I. 1.2, 5.7]). Conclusion: This is the first large prospective study on women with HG. Women with HG, particularly severe HG, are at increased risk of cognitive, behavioural and emotional dysfunction in pregnancy. Women with severe HG had a higher rate of spontaneous preterm birth compared to women without HG. Further research is required to determine whether the provision of emotional support for women with HG is beneficial.Fergus P. McCarthy, Ali S. Khashan, Robyn A. North, Rona Moss-Morris, Philip N. Baker, Gus Dekker, Lucilla Poston, Louise C. Kenny on behalf of the SCOPE consortiu

Clinical risk prediction for pre-eclampsia in nulliparous women: development of model in international prospective cohort

Objectives To develop a predictive model for pre-eclampsia based on clinical risk factors for nulliparous women and to identify a subgroup at increased risk, in whom specialist referral might be indicated

Prediction of Small for Gestational Age Infants in Healthy Nulliparous Women Using Clinical and Ultrasound Risk Factors Combined with Early Pregnancy Biomarkers

Objective Most small for gestational age pregnancies are unrecognised before birth, resulting in substantial avoidable perinatal mortality and morbidity. Our objective was to develop multivariable prediction models for small for gestational age combining clinical risk factors and biomarkers at 15±1 weeks’ with ultrasound parameters at 20±1 weeks’ gestation. Methods Data from 5606 participants in the Screening for Pregnancy Endpoints (SCOPE) cohort study were divided into Training (n = 3735) and Validation datasets (n = 1871). The primary outcomes were All-SGA (small for gestational age with birthweight <10th customised centile), Normotensive-SGA (small for gestational age with a normotensive mother) and Hypertensive-SGA (small for gestational age with an hypertensive mother). The comparison group comprised women without the respective small for gestational age phenotype. Multivariable analysis was performed using stepwise logistic regression beginning with clinical variables, and subsequent additions of biomarker and then ultrasound (biometry and Doppler) variables. Model performance was assessed in Training and Validation datasets by calculating area under the curve. Results 633 (11.2%) infants were All-SGA, 465(8.2%) Normotensive-SGA and 168 (3%) Hypertensive-SGA. Area under the curve (95% Confidence Intervals) for All-SGA using 15±1 weeks’ clinical variables, 15±1 weeks’ clinical+ biomarker variables and clinical + biomarkers + biometry /Doppler at 20±1 weeks’ were: 0.63 (0.59–0.67), 0.64 (0.60–0.68) and 0.69 (0.66–0.73) respectively in the Validation dataset; Normotensive-SGA results were similar: 0.61 (0.57–0.66), 0.61 (0.56–0.66) and 0.68 (0.64–0.73) with small increases in performance in the Training datasets. Area under the curve (95% Confidence Intervals) for Hypertensive-SGA were: 0.76 (0.70–0.82), 0.80 (0.75–0.86) and 0.84 (0.78–0.89) with minimal change in the Training datasets. Conclusion Models for prediction of small for gestational age, which combine biomarkers, clinical and ultrasound data from a cohort of low-risk nulliparous women achieved modest performance. Incorporation of biomarkers into the models resulted in no improvement in performance of prediction of All-SGA and Normotensive-SGA but a small improvement in prediction of Hypertensive-SGA. Our models currently have insufficient reliability for application in clinical practice however, they have potential utility in two-staged screening tests which include third trimester biomarkers and or fetal biometry

Evaluating a team-based approach to research capacity building using a matched-pairs study design

Background: There is a continuing need for research capacity building initiatives for primary health care professionals. Historically strategies have focused on interventions aimed at individuals but more recently theoretical frameworks have proposed team-based approaches. Few studies have evaluated these new approaches. This study aims to evaluate a team-based approach to research capacity building (RCB) in primary health using a validated quantitative measure of research capacity in individual, team and organisation domains

Novel measures of cardiovascular health and its association with prevalence and progression of age-related macular degeneration: the CHARM study

<p>Abstract</p> <p>Background</p> <p>To determine if novel measures of cardiovascular health are associated with prevalence or progression of age-related macular degeneration (AMD).</p> <p>Methods</p> <p>Measures of the cardiovascular system: included intima media thickness (IMT), pulse wave velocity (PWV), systemic arterial compliance (SAC), carotid augmentation index (AI). For the prevalence study, hospital-based AMD cases and population-based age- and gender-matched controls with no signs of AMD in either eye were enrolled. For the progression component, participants with early AMD were recruited from two previous studies; cases were defined as progression in one or both eyes and controls were defined as no progression in either eye.</p> <p>Results</p> <p>160 cases and 160 controls were included in the prevalence component. The upper two quartiles of SAC, implying good cardiovascular health, were significantly associated with increased risk of AMD (OR = 2.54, 95% CL = 1.29, 4.99). High PWV was associated with increased prevalent AMD. Progression was observed in 82 (32.3%) of the 254 subjects recruited for the progression component. Higher AI (worse cardiovascular function) was protective for AMD progression (OR = 0.30, 95%CL = 0.13, 0.69). Higher aortic PWV was associated with increased risk of AMD progression; the highest risk was seen with the second lowest velocity (OR = 6.22, 95% CL = 2.35, 16.46).</p> <p>Conclusion</p> <p>The results were unexpected in that better cardiovascular health was associated with increased risk of prevalent AMD and progression. Inconsistent findings between the prevalence and progression components could be due to truly different disease etiologies or to spurious findings, as can occur with inherent biases in case control studies of prevalence. Further investigation of these non-invasive methods of characterizing the cardiovascular system should be undertaken as they may help to further elucidate the role of the cardiovascular system in the etiology of prevalent AMD and progression.</p

Risk factors for preterm birth in an international prospective cohort of nulliparous women

To identify risk factors for spontaneous preterm birth (birth ,37 weeks gestation) with intact membranes(SPTB-IM) and SPTB after prelabour rupture of the membranes (SPTB-PPROM) for nulliparous pregnant women. DESIGN: Prospective international multicentre cohort. PARTICIPANTS: 3234 healthy nulliparous women with a singleton pregnancy, follow up was complete in 3184 of participants (98.5%). RESULTS: Of the 3184 women, 156 (4.9%) had their pregnancy complicated by SPTB; 96 (3.0%) and 60 (1.9%) in the SPTB-IM and SPTB-PPROM categories, respectively. Independent risk factors for SPTB-IM were shorter cervical length, abnormal uterine Doppler flow, use of marijuana pre-pregnancy, lack of overall feeling of well being, being of Caucasian ethnicity, having a mother with diabetes and/or a history of preeclampsia, and a family history of low birth weight babies. Independent risk factors for SPTB-PPROM were shorter cervical length, short stature, participant’s not being the first born in the family, longer time to conceive, not waking up at night, hormonal fertility treatment (excluding clomiphene), mild hypertension, family history of recurrent gestational diabetes, and maternal family history of any miscarriage (risk reduction). Low BMI (<20) nearly doubled the risk for SPTB-PPROM (odds ratio 2.64; 95% CI 1.07–6.51). The area under the receiver operating characteristics curve (AUC), after internal validation, was 0.69 for SPTB-IM and 0.79 for SPTB-PPROM. CONCLUSION: The ability to predict PTB in healthy nulliparous women using clinical characteristics is modest. The dissimilarity of risk factors for SPTB-IM compared with SPTB-PPROM indicates different pathophysiological pathways underlie these distinct phenotypes.Gustaaf Albert Dekker, Shalem Y. Lee, Robyn A. North, Lesley M. McCowan, Nigel A.B. Simpson and Claire T. Robert