PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (40)
 

Clipboard (0)
None

Select a Filter Below

Year of Publication
more »
2.  The INTERGROWTH-21st Project Neurodevelopment Package: A Novel Method for the Multi-Dimensional Assessment of Neurodevelopment in Pre-School Age Children 
PLoS ONE  2014;9(11):e113360.
Background
The International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) Project is a population-based, longitudinal study describing early growth and development in an optimally healthy cohort of 4607 mothers and newborns. At 24 months, children are assessed for neurodevelopmental outcomes with the INTERGROWTH-21st Neurodevelopment Package. This paper describes neurodevelopment tools for preschoolers and the systematic approach leading to the development of the Package.
Methods
An advisory panel shortlisted project-specific criteria (such as multi-dimensional assessments and suitability for international populations) to be fulfilled by a neurodevelopment instrument. A literature review of well-established tools for preschoolers revealed 47 candidates, none of which fulfilled all the project's criteria. A multi-dimensional assessment was, therefore, compiled using a package-based approach by: (i) categorizing desired outcomes into domains, (ii) devising domain-specific criteria for tool selection, and (iii) selecting the most appropriate measure for each domain.
Results
The Package measures vision (Cardiff tests); cortical auditory processing (auditory evoked potentials to a novelty oddball paradigm); and cognition, language skills, behavior, motor skills and attention (the INTERGROWTH-21st Neurodevelopment Assessment) in 35–45 minutes. Sleep-wake patterns (actigraphy) are also assessed. Tablet-based applications with integrated quality checks and automated, wireless electroencephalography make the Package easy to administer in the field by non-specialist staff. The Package is in use in Brazil, India, Italy, Kenya and the United Kingdom.
Conclusions
The INTERGROWTH-21st Neurodevelopment Package is a multi-dimensional instrument measuring early child development (ECD). Its developmental approach may be useful to those involved in large-scale ECD research and surveillance efforts.
doi:10.1371/journal.pone.0113360
PMCID: PMC4244160  PMID: 25423589
3.  MULTI-CENTRE STUDIES OF THE GLOBAL IMPACT OF ENDOMETRIOSIS AND THE PREDICTIVE VALUE OF ASSOCIATED SYMPTOMS 
Journal of endometriosis  2009;1(1):36-45.
Introduction
Endometriosis can be difficult to diagnose clinically and models that use symptoms to predict whether the disease is present or not are based on limited patient populations. Endometriosis also influences health-related quality of life, but little is known about its impact across the world. We therefore initiated two integrated multicentre studies to collect prospective, standardised, epidemiological data, to 1) examine the global impact of endometriosis and relative effect of risk-factors, and 2) develop a symptom-based diagnostic tool.
Methods
The Global Study of Women’s Health (GSWH) and the Women’s Health Symptom Survey (WHSS) prospectively recruit 18-45 year old women having a laparoscopy across 23 and 19 centres, respectively, worldwide. Women with a previous surgical diagnosis of endometriosis are excluded. Multi-lingual patient questionnaires and a surgical questionnaire, incorporating validated instruments, are used to collect the data. The GSWH aims to recruit >2,000 women by December 2009; the WHSS to recruit 1,000 women in each of the two model-generating and validation stages.
Results
A six-week pilot study in Oxford, UK, established the feasibility of the study protocols. Of 32 eligible women, 27 participated (response rate - 84.4%); 26% completed the questionnaire online. Endometriosis was found in 47.4%. Extrapolating the recruitment rates from the pilot study, the target sample sizes for the GWSH and WHSS were deemed feasible.
Conclusions
Using standardised data collection, the GSWH and WHSS will provide insight into the global impact of endometriosis and develop a validated, symptom-based, diagnostic tool. They have the potential to provide the basis for future, longitudinal, follow-up studies and a collaborative Endometriosis Biobank implementing standardised collection of DNA and tissue samples.
PMCID: PMC4197400  PMID: 25328660
Endometriosis; Global; Quality of life; Pelvic pain; Infertility; Symptom; Diagnostic tool; Epidemiology
4.  Common variants in the CYP2C19 gene are associated with susceptibility to endometriosis 
Fertility and sterility  2014;102(2):496-502.e5.
Objective
To follow-up previous studies highlighting a possible role for cytochrome P450, family 2, subfamily C, 19 (CYP2C19) in susceptibility to endometriosis by searching for additional variants in the CYP2C19 gene that may be associated with the disease.
Design
Case-control study.
Setting
Academic research.
Subject(s)
Cases = 2,271 women with surgically confirmed endometriosis; Controls = 939 women with self-report of no endometriosis and 1,770 unscreened population samples.
Intervention(s)
Sequencing of the CYP2C19 region and follow-up of 80 SNPs in two case-control samples.
Main outcome measure(s)
Allele frequency differences between cases and controls.
Results
Sequencing of the CYP2C19 gene region resulted in the detection of a large number of known and novel SNPs. Genotyping of 80 polymorphic SNPs in 901 endometriosis cases and 939 controls resulted in study-wide significant association signals for SNPs in moderate or complete LD with rs4244285, a functional SNP in exon 5 that abrogates CYP2C19 function through the creation of an alternative splice site. Evidence of association was also detected for another functional SNP in the CYP2C19 promoter, rs12248560, highlighted in our previous study.
Conclusion(s)
Functional variants in CYP2C19 may contribute to endometriosis susceptibility in both familial and sporadic cases.
doi:10.1016/j.fertnstert.2014.04.015
PMCID: PMC4150687  PMID: 24796765
Endometriosis; association; pooled sequencing; CYP2C19; rs12248560; rs4244285
5.  Effectiveness of a Brief Condom Promotion Program in Reducing Risky Sexual Behaviors among African American Males 
doi:10.1111/j.1365-2753.2012.01841.x
PMCID: PMC3382027  PMID: 22435646
Condom Promotion Program; African American Males; Minority Health; Intervention Research; HIV/STDs; Condom Use Behavior
6.  Cationic Peptide Exposure Enhances Pulsed-Electric-Field-Mediated Membrane Disruption 
PLoS ONE  2014;9(3):e92528.
Background
The use of pulsed electric fields (PEFs) to irreversibly electroporate cells is a promising approach for destroying undesirable cells. This approach may gain enhanced applicability if the intensity of the PEF required to electrically disrupt cell membranes can be reduced via exposure to a molecular deliverable. This will be particularly impactful if that reduced PEF minimally influences cells that are not exposed to the deliverable. We hypothesized that the introduction of charged molecules to the cell surfaces would create regions of enhanced transmembrane electric potential in the vicinity of each charged molecule, thereby lowering the PEF intensity required to disrupt the plasma membranes. This study will therefore examine if exposure to cationic peptides can enhance a PEF’s ability to disrupt plasma membranes.
Methodology/Principal Findings
We exposed leukemia cells to 40 μs PEFs in media containing varying concentrations of a cationic peptide, polyarginine. We observed the internalization of a membrane integrity indicator, propidium iodide (PI), in real time. Based on an individual cell’s PI fluorescence versus time signature, we were able to determine the relative degree of membrane disruption. When using 1–2 kV/cm, exposure to >50 μg/ml of polyarginine resulted in immediate and high levels of PI uptake, indicating severe membrane disruption, whereas in the absence of peptide, cells predominantly exhibited signatures indicative of no membrane disruption. Additionally, PI entered cells through the anode-facing membrane when exposed to cationic peptide, which was theoretically expected.
Conclusions/Significance
Exposure to cationic peptides reduced the PEF intensity required to induce rapid and irreversible membrane disruption. Critically, peptide exposure reduced the PEF intensities required to elicit irreversible membrane disruption at normally sub-electroporation intensities. We believe that these cationic peptides, when coupled with current advancements in cell targeting techniques will be useful tools in applications where targeted destruction of unwanted cell populations is desired.
doi:10.1371/journal.pone.0092528
PMCID: PMC3966810  PMID: 24671150
7.  HIV/STD Risk Behaviors Among In-School Adolescents in Post-Conflict Liberia 
We conducted a randomized trial to address the health needs of in-school adolescents in Liberia, where we analyzed data from a behavioral survey administered to 820 students from 8 urban schools. Our findings suggest that adolescents are at significant risk for HIV and other sexually transmitted diseases (STDs): 36% of respondents were sexually experienced, 34% of those had first sex at ages 14 or younger, and 66% of first sexual encounters were unprotected while 16% were described as “forced.” Also, females were more likely to have older boyfriends (Pearson chi square = 19.2, p = 0.0001) and sex resulting into pregnancies (Pearson chi square = 11.5, p = 0.01), while males were more likely to have a greater number of sexual partners (Pearson chi square = 5.6, p = 0.05) in the previous 3 months. We recommend further research to explore challenges associated with implementing behavioral-driven studies in post-conflict environments.
doi:10.1016/j.jana.2011.05.005
PMCID: PMC3244556  PMID: 21924644
adolescents; HIV/STDs; Liberia; post-conflict setting; school; sub-Saharan Africa
8.  Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries 
Fertility and sterility  2011;96(2):366-373.e8.
Objective
To assess the impact of endometriosis on health-related quality of life (HRQoL) and work productivity.
Design
Multicenter cross-sectional study with prospective recruitment.
Setting
Sixteen clinical centers in ten countries.
Patient(s)
A total of 1,418 premenopausal women, aged 18–45 years, without a previous surgical diagnosis of endometriosis, having laparoscopy to investigate symptoms or to be sterilized.
Intervention(s)
None.
Main Outcome Measure(s)
Diagnostic delay, HRQoL, and work productivity.
Result(s)
There was a delay of 6.7 years, principally in primary care, between onset of symptoms and a surgical diagnosis of endometriosis, which was longer in centers where women received predominantly state-funded health care (8.3 vs. 5.5 years). Delay was positively associated with the number of pelvic symptoms (chronic pelvic pain, dysmenorrhoea, dyspareunia, and heavy periods) and a higher body mass index. Physical HRQoL was significantly reduced in affected women compared with those with similar symptoms and no endometriosis. Each affected woman lost on average 10.8 hours (SD 12.2) of work weekly, mainly owing to reduced effectiveness while working. Loss of work productivity translated into significant costs per woman/week, from US$4 in Nigeria to US$456 in Italy.
Conclusion(s)
Endometriosis impairs HRQoL and work productivity across countries and ethnicities, yet women continue to experience diagnostic delays in primary care. A higher index of suspicion is needed to expedite specialist assessment of symptomatic women. Future research should seek to clarify pain mechanisms in relation to endometriosis severity.
doi:10.1016/j.fertnstert.2011.05.090
PMCID: PMC3679489  PMID: 21718982
Endometriosis; quality of life; work productivity
9.  Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study 
Fertility and sterility  2012;98(3):692-701.e5.
Objective
To generate and validate symptom-based models to predict endometriosis among symptomatic women prior to undergoing their first laparoscopy.
Design
Prospective, observational, two-phase study, in which women completed a 25-item questionnaire prior to surgery.
Setting
Nineteen hospitals in 13 countries.
Patient(s)
Symptomatic women (n = 1,396) scheduled for laparoscopy without a previous surgical diagnosis of endometriosis.
Intervention(s)
None.
Main Outcome Measure(s)
Sensitivity and specificity of endometriosis diagnosis predicted by symptoms and patient characteristics from optimal models developed using multiple logistic regression analyses in one data set (phase I), and independently validated in a second data set (phase II) by receiver operating characteristic (ROC) curve analysis.
Result(s)
Three hundred sixty (46.7%) women in phase I and 364 (58.2%) in phase II were diagnosed with endometriosis at laparoscopy. Menstrual dyschezia (pain on opening bowels) and a history of benign ovarian cysts most strongly predicted both any and stage III and IV endometriosis in both phases. Prediction of any-stage endometriosis, although improved by ultrasound scan evidence of cyst/nodules, was relatively poor (area under the curve [AUC] = 68.3). Stage III and IV disease was predicted with good accuracy (AUC = 84.9, sensitivity of 82.3% and specificity 75.8% at an optimal cut-off of 0.24).
Conclusion(s)
Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy. Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis. We invite other researchers to validate the key models in additional populations.
doi:10.1016/j.fertnstert.2012.04.022
PMCID: PMC3679490  PMID: 22657249
Endometriosis; predictive model; logistic regression
10.  Why Are Women Dying When They Reach Hospital on Time? A Systematic Review of the ‘Third Delay’ 
PLoS ONE  2013;8(5):e63846.
Background
The ‘three delays model’ attempts to explain delays in women accessing emergency obstetric care as the result of: 1) decision-making, 2) accessing services and 3) receipt of appropriate care once a health facility is reached. The third delay, although under-researched, is likely to be a source of considerable inequity in access to emergency obstetric care in developing countries. The aim of this systematic review was to identify and categorise specific facility-level barriers to the provision of evidence-based maternal health care in developing countries.
Methods and Findings
Five electronic databases were systematically searched using a 4-way strategy that combined search terms related to: 1) maternal health care; 2) maternity units; 3) barriers, and 4) developing countries. Forty-three original research articles were eligible to be included in the review. Thirty-two barriers to the receipt of timely and appropriate obstetric care at the facility level were identified and categorised into six emerging themes (Drugs and equipment; Policy and guidelines; Human resources; Facility infrastructure; Patient-related and Referral-related). Two investigators independently recorded the frequency with which barriers relating to the third delay were reported in the literature. The most commonly cited barriers were inadequate training/skills mix (86%); drug procurement/logistics problems (65%); staff shortages (60%); lack of equipment (51%) and low staff motivation (44%).
Conclusions
This review highlights how a focus on patient-side delays in the decision to seek care can conceal the fact that many health facilities in the developing world are still chronically under-resourced and unable to cope effectively with serious obstetric complications. We stress the importance of addressing supply-side barriers alongside demand-side factors if further reductions in maternal mortality are to be achieved.
doi:10.1371/journal.pone.0063846
PMCID: PMC3660500  PMID: 23704943
11.  Reducing sexual risk taking behaviors among adolescents who engage in transactional sex in post-conflict Liberia 
Transactional sex (TS) has been correlated with HIV/STD infection, pregnancy, early marriage, and sexual violence in sub-Saharan Africa (SSA). Few Western-based HIV prevention programs adapted for SSA have examined intervention impacts for this group. This article examines whether an HIV prevention intervention, delivered to sixth-grade students in Liberia (age range 14–17) and found to increase condom use and other mediators for the larger sample, significantly impacted sexual behaviors and mediators for those who engaged in TS. Using an attention-matched, group-randomized controlled design, four matched pairs of elementary schools in Monrovia, Liberia, were randomly assigned to an adapted eight-module HIV prevention or a general health curriculum. Nine-month impacts of the intervention on sexual risk behaviors and mediators for those who engaged in TS, when compared with other study participants, are presented. Twelve percent of our sample of sixth graders (n = 714) ever engaged in TS. The majority of females reported being promised something in exchange for sex (52%), whereas the majority of males (52%) reported being both the giver and recipient of gifts in exchange for sex. Compared with other students, those who engaged in TS reported greater increases in the number of sex partners, reported greater frequency of sexual intercourse, were more likely to try to get pregnant or someone else pregnant, and reported greater reductions in protective sexual attitudes and HIV risk perception at the nine month follow-up, in both the intervention and the control groups. Our intervention, although successful for the general in-school adolescent sample, did not impact risk behaviors or mediators for adolescents who engaged in TS. Future research should explore the complex sexual economy in which TS is embedded and consider adapting HIV prevention interventions to the needs of this high-risk group.
doi:10.1080/17450128.2011.647773
PMCID: PMC3634670  PMID: 23626654
adolescents; AIDS; Liberia; prevention; transactional sex
12.  IMPACT OF SCHOOL-BASED HIV PREVENTION PROGRAM IN POST-CONFLICT LIBERIA 
This paper presents findings of a feasibility study to adapt and evaluate the impact of an evidence-based HIV prevention intervention on sexual risk behaviors of in-school 6th grade youth in post-conflict Liberia (n = 812). The study used an attention-matched, group randomized controlled trial. Four matched pairs of elementary/middle schools in Monrovia, Liberia, were randomly assigned to either an adapted eight-module HIV prevention or a general health curriculum. Three- and nine-month impacts of the intervention on sexual risk behaviors and on mediating variables are presented. The intervention significantly impacted protective peer norms and positive condom attitudes and increased frequency of condom use at the nine-month follow-up. The intervention did not impact sexual initiation or multiple sex partnerships. Future intervention research should address the salient pressures that are unique to post-conflict settings and include longer follow-up time periods and smaller class sizes to meaningfully impact sexual initiation and multiple sex partnerships.
doi:10.1521/aeap.2012.24.1.68
PMCID: PMC3633464  PMID: 22339146
14.  Genome-wide association meta-analysis identifies new endometriosis risk loci 
Nature genetics  2012;44(12):1355-1359.
We conducted a genome-wide association (GWA) meta-analysis of 4,604 endometriosis cases and 9,393 controls of Japanese1 and European2 ancestry. We show that rs12700667 on chromosome 7p15.2, previously found in Europeans, replicates in Japanese (P = 3.6 × 10−3), and confirm association of rs7521902 on 1p36.12 near WNT4. In addition, we establish association of rs13394619 in GREB1 on 2p25.1 and identify a novel locus on 12q22 near VEZT (rs10859871). Excluding European cases with minimal or unknown severity, we identified additional novel loci on 2p14 (rs4141819), 6p22.3 (rs7739264) and 9p21.3 (rs1537377). All seven SNP effects were replicated in an independent cohort and produced P < 5 × 10−8 in a combined analysis. Finally, we found a significant overlap in polygenic risk for endometriosis between the European and Japanese GWA cohorts (P = 8.8 × 10−11), indicating that many weakly associated SNPs represent true endometriosis risk loci and risk prediction and future targeted disease therapy may be transferred across these populations.
doi:10.1038/ng.2445
PMCID: PMC3527416  PMID: 23104006
15.  No evidence for genetic association with the let-7 microRNA-binding site or other common KRAS variants in risk of endometriosis 
Human Reproduction (Oxford, England)  2012;27(12):3616-3621.
STUDY QUESTION
Is there a contribution of the minor allele at the KRAS single nucleotide polymorphism (SNP) rs61764370 in the let-7 microRNA-binding site to endometriosis risk?
SUMMARY ANSWER
We found no evidence for association between endometriosis risk and rs61764370 or any other SNPs in KRAS.
WHAT IS KNOWN ALREADY
The rs61764370 SNP in the 3′ untranslated region of the KRAS gene is predicted to disrupt a complementary binding site (LCS6) for the let-7 microRNA, and was recently reported to be at a high frequency (31%) in 132 women of varying ancestry with endometriosis compared with frequencies in a database of population controls (up to 7.6% depending on ancestry), suggesting a strong effect of this KRAS SNP in the aetiology of endometriosis.
STUDY DESIGN, SIZE AND DURATION
This was a case–control study with a total of 11 206 subjects. The study was performed between February 2012 and July 2012.
PARTICIPANTS/MATERIALS, SETTING AND METHODS
We first investigated a possible association between common markers in KRAS and endometriosis risk from our genome-wide association (GWA) data in 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry. Although rs61764370 was not genotyped on the GWA arrays, five SNPs typed in the study were highly correlated with this variant. The rs61764370 and two SNPs highly correlated with rs61764370 were then genotyped in 933 endometriosis cases and 952 controls using the Sequenom MassARRAY platform.
MAIN RESULTS AND THE ROLE OF CHANCE
There was no evidence for an association between rs61764370 and endometriosis risk P = 0.411 and odds ratio = 1.10 (95% confidence intervals: 0.88–1.36). We also found no evidence for an association between the highly correlated SNP rs17387019 and endometriosis. Their minor allele frequencies in cases and controls were of 0.087–0.091 similar to the population frequency reported previously for this variant in controls. Analyses of endometriosis cases with revised American Fertility Society stage III/IV disease also showed no evidence for an association between these SNPs and endometriosis risk.
LIMITATIONS AND REASONS FOR CAUTION
The GWA and genotyped data sets were not independent since individuals and cases from some families overlap. Controls in our GWA study were not screened for endometriosis.
WIDER IMPLICATIONS OF THE FINDINGS
The key SNP, rs61764370, was genotyped in a subset of samples. Our results do not support the suggestion that carrying the minor allele at rs61764370 contributes to a significant number of endometriosis cases and rs61764370 is, therefore, unlikely to be a useful marker of endometriosis risk.
STUDY FUNDING/COMPETING INTEREST(S)
The research was funded by grants from the Australian National Health and Medical Research Council and Wellcome Trust. None of the authors has competing interests for the study.
doi:10.1093/humrep/des329
PMCID: PMC3501245  PMID: 23010532
endometriosis; KRAS; microRNA; genetic association
16.  Is early age at menarche a risk factor for endometriosis? A systematic review and meta-analysis of case-control studies 
Fertility and Sterility  2012;98(3):702-712.e6.
Objective
To review published studies evaluating early menarche and the risk of endometriosis.
Design
Systematic review and meta-analysis of case-control studies.
Setting
None.
Patient(s)
Eighteen case-control studies of age at menarche and risk of endometriosis including 3,805 women with endometriosis and 9,526 controls.
Intervention(s)
None.
Main Outcome Measure(s)
Medline and Embase databases were searched from 1980 to 2011 to locate relevant studies. Results of primary studies were expressed as effect sizes of the difference in mean age at menarche of women with and without endometriosis. Effect sizes were used in random effects meta-analysis.
Result(s)
Eighteen of 45 articles retrieved met the inclusion criteria. The pooled effect size in meta-analysis was 0.10 (95% confidence interval −0.01–0.21), and not significantly different from zero (no effect). Results were influenced by substantial heterogeneity between studies (I2 = 72.5%), which was eliminated by restricting meta-analysis to studies with more rigorous control of confounders; this increased the pooled effect size to 0.15 (95% confidence interval 0.08–0.22), which was significantly different from zero. This represents a probability of 55% that a woman with endometriosis had earlier menarche than one without endometriosis if both were randomly chosen from a population.
Conclusion(s)
There is a small increased risk of endometriosis with early menarche. The potential for disease misclassification in primary studies suggests that this risk could be higher.
doi:10.1016/j.fertnstert.2012.05.035
PMCID: PMC3502866  PMID: 22728052
Endometriosis; menarche; systematic review; meta-analysis
17.  Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study 
Fertility and Sterility  2012;98(3):692-701.e5.
Objective
To generate and validate symptom-based models to predict endometriosis among symptomatic women prior to undergoing their first laparoscopy.
Design
Prospective, observational, two-phase study, in which women completed a 25-item questionnaire prior to surgery.
Setting
Nineteen hospitals in 13 countries.
Patient(s)
Symptomatic women (n = 1,396) scheduled for laparoscopy without a previous surgical diagnosis of endometriosis.
Intervention(s)
None.
Main Outcome Measure(s)
Sensitivity and specificity of endometriosis diagnosis predicted by symptoms and patient characteristics from optimal models developed using multiple logistic regression analyses in one data set (phase I), and independently validated in a second data set (phase II) by receiver operating characteristic (ROC) curve analysis.
Result(s)
Three hundred sixty (46.7%) women in phase I and 364 (58.2%) in phase II were diagnosed with endometriosis at laparoscopy. Menstrual dyschezia (pain on opening bowels) and a history of benign ovarian cysts most strongly predicted both any and stage III and IV endometriosis in both phases. Prediction of any-stage endometriosis, although improved by ultrasound scan evidence of cyst/nodules, was relatively poor (area under the curve [AUC] = 68.3). Stage III and IV disease was predicted with good accuracy (AUC = 84.9, sensitivity of 82.3% and specificity 75.8% at an optimal cut-off of 0.24).
Conclusion(s)
Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy. Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis. We invite other researchers to validate the key models in additional populations.
doi:10.1016/j.fertnstert.2012.04.022
PMCID: PMC3679490  PMID: 22657249
Endometriosis; predictive model; logistic regression
18.  High-density fine-mapping of a chromosome 10q26 linkage peak suggests association between endometriosis and variants close to CYP2C19 
Fertility and sterility  2011;95(7):2236-2240.
Objective
To refine a previously reported linkage peak for endometriosis on chromosome 10q26, and conduct follow-up analyses and a fine-mapping association study across the region to identify new candidate genes for endometriosis.
Design
Case-control study.
Setting
Academic research.
Subject(s)
Cases = 3,223 women with surgically confirmed endometriosis; Controls = 1,190 women without endometriosis and 7,060 population samples.
Intervention(s)
Analysis of 11,984 SNPs on chromosome 10.
Main outcome measure(s)
Allele frequency differences between cases and controls.
Results
Linkage analyses on families grouped by endometriosis symptoms (primarily subfertility) provided increased evidence for linkage (logarithm of odds (LOD) score = 3.62) near a previously reported linkage peak. Three independent association signals were found at 96.59 Mb (rs11592737, P=4.9 × 10−4), 105.63 Mb (rs1253130, P=2.5 × 10−4) and 124.25 Mb (rs2250804, P=9.7 × 10−4). Analyses including only samples from linkage families supported the association at all three regions. However, only rs11592737 in the cytochrome P450 subfamily C (CYP2C19) gene was replicated in an independent sample of 2,079 cases and 7060 population controls.
Conclusion(s)
The role of the CYP2C19 gene in conferring risk for endometriosis warrants further investigation.
doi:10.1016/j.fertnstert.2011.03.062
PMCID: PMC3125525  PMID: 21497341
Endometriosis; linkage; association; subfertility; CYP2C19
19.  Fertility Preservation in Girls 
Children that undergo treatment for cancer are at risk of suffering from subfertility or hormonal dysfunction due to the detrimental effects of radiotherapy and chemotherapeutic agents on the gonads. Cryopreservation of ovarian tissue prior to treatment offers the possibility of restoring gonadal function after resumption of therapy. Effective counseling and management of pediatric patients is crucial for preserving their future reproductive potential. The purpose of this article is to review recent literature and to revise recommendations we made in a 2007 article. Pediatric hemato-oncology, reproductive endocrinology, surgery, anesthesia and bioethics perspectives are discussed and integrated to propose guidelines for offering ovarian cryopreservation to premenarcheal girls with cancer.
doi:10.1155/2012/139193
PMCID: PMC3307018  PMID: 22496695
20.  Ultrasound Evidence of Early Fetal Growth Restriction after Maternal Malaria Infection 
PLoS ONE  2012;7(2):e31411.
Background
Intermittent preventive treatment (IPT), the main strategy to prevent malaria and reduce anaemia and low birthweight, focuses on the second half of pregnancy. However, intrauterine growth restriction may occur earlier in pregnancy. The aim of this study was to measure the effects of malaria in the first half of pregnancy by comparing the fetal biparietal diameter (BPD) of infected and uninfected women whose pregnancies had been accurately dated by crown rump length (CRL) before 14 weeks of gestation.
Methodology/Principal Findings
In 3,779 women living on the Thai-Myanmar border who delivered a normal singleton live born baby between 2001–10 and who had gestational age estimated by CRL measurement <14 weeks, the observed and expected BPD z-scores (<24 weeks) in pregnancies that were (n = 336) and were not (n = 3,443) complicated by malaria between the two scans were compared. The mean (standard deviation) fetal BPD z-scores in women with Plasmodium (P) falciparum and/or P.vivax malaria infections were significantly lower than in non-infected pregnancies; −0.57 (1.13) versus −0.10 (1.17), p<0.001. Even a single or an asymptomatic malaria episode resulted in a significantly lower z-score. Fetal female sex (p<0.001) and low body mass index (p = 0.01) were also independently associated with a smaller BPD in multivariate analysis.
Conclusions/Significance
Despite early treatment in all positive women, one or more (a)symptomatic P.falciparum or P.vivax malaria infections in the first half of pregnancy result in a smaller than expected mid-trimester fetal head diameter. Strategies to prevent malaria in pregnancy should include early pregnancy.
doi:10.1371/journal.pone.0031411
PMCID: PMC3276538  PMID: 22347473
21.  MAVIDOS Maternal Vitamin D Osteoporosis Study: study protocol for a randomized controlled trial. The MAVIDOS Study Group 
Trials  2012;13:13.
MAVIDOS is a randomised, double-blind, placebo-controlled trial (ISRCTN82927713, registered 2008 Apr 11), funded by Arthritis Research UK, MRC, Bupa Foundation and NIHR.
Background
Osteoporosis is a major public health problem as a result of associated fragility fractures. Skeletal strength increases from birth to a peak in early adulthood. This peak predicts osteoporosis risk in later life. Vitamin D insufficiency in pregnancy is common (31% in a recent Southampton cohort) and predicts reduced bone mass in the offspring. In this study we aim to test whether offspring of mothers supplemented with vitamin D in pregnancy have higher bone mass at birth than those whose mothers were not supplemented.
Methods/Design
Women have their vitamin D status assessed after ultrasound scanning in the twelfth week of pregnancy at 3 trial centres (Southampton, Sheffield, Oxford). Women with circulating 25(OH)-vitamin D levels 25-100 nmol/l are randomised in a double-blind design to either oral vitamin D supplement (1000 IU cholecalciferol/day, n = 477) or placebo at 14 weeks (n = 477). Questionnaire data include parity, sunlight exposure, dietary information, and cigarette and alcohol consumption. At 19 and 34 weeks maternal anthropometry is assessed and blood samples taken to measure 25(OH)-vitamin D, PTH and biochemistry. At delivery venous umbilical cord blood is collected, together with umbilical cord and placental tissue. The babies undergo DXA assessment of bone mass within the first 14 days after birth, with the primary outcome being whole body bone mineral content adjusted for gestational age and age. Children are then followed up with yearly assessment of health, diet, physical activity and anthropometric measures, with repeat assessment of bone mass by DXA at age 4 years.
Discussion
As far as we are aware, this randomised trial is one of the first ever tests of the early life origins hypothesis in human participants and has the potential to inform public health policy regarding vitamin D supplementation in pregnancy. It will also provide a valuable resource in which to study the influence of maternal vitamin D status on other childhood outcomes such as glucose tolerance, blood pressure, cardiovascular function, IQ and immunology.
doi:10.1186/1745-6215-13-13
PMCID: PMC3395865  PMID: 22314083
Vitamin D; cholecalciferol; supplementation; trial; osteoporosis; DXA; pregnancy; neonate
22.  Effect of malaria on placental volume measured using three-dimensional ultrasound: a pilot study 
Malaria Journal  2012;11:5.
Background
The presence of malaria parasites and histopathological changes in the placenta are associated with a reduction in birth weight, principally due to intrauterine growth restriction. The aim of this study was to examine the feasibility of studying early pregnancy placental volumes using three-dimensional (3D) ultrasound in a malaria endemic area, as a small volume in the second trimester may be an indicator of intra-uterine growth restriction and placental insufficiency.
Methods
Placenta volumes were acquired using a portable ultrasound machine and a 3D ultrasound transducer and estimated using the Virtual Organ Computer-aided AnaLysis (VOCAL) image analysis software package. Intra-observer reliability and limits of agreement of the placenta volume measurements were calculated. Polynomial regression models for the mean and standard deviation as a function of gestational age for the placental volumes of uninfected women were created and tested. Based on these equations each measurement was converted into a z -score. The z-scores of the placental volumes of malaria infected and uninfected women were then compared.
Results
Eighty-four women (uninfected = 65; infected = 19) with a posterior placenta delivered congenitally normal, live born, single babies. The mean placental volumes in the uninfected women were modeled to fit 5th, 10th, 50th, 90th and 95th centiles for 14-24 weeks' gestation. Most placenta volumes in the infected women were below the 50th centile for gestational age; most of those with Plasmodium falciparum were below the 10th centile. The 95% intra-observer limits of agreement for first and second measurements were ± 37.0 mL and ± 25.4 mL at 30 degrees and 15 degrees rotation respectively.
Conclusion
The new technique of 3D ultrasound volumetry of the placenta may be useful to improve our understanding of the pathophysiological constraints on foetal growth caused by malaria infection in early pregnancy.
doi:10.1186/1475-2875-11-5
PMCID: PMC3317826  PMID: 22222152
Malaria; Pregnancy; Three-dimensional ultrasound; Placenta volume; IUGR
23.  Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis 
Nature genetics  2010;43(1):51-54.
Endometriosis is a common gynaecological disease associated with pelvic pain and sub-fertility. We conducted a genome-wide association (GWA) study in 3,194 surgically confirmed endometriosis cases and 7,060 controls from Australia and the UK. Polygenic predictive modelling showed significantly increased genetic loading among 1,364 cases with moderate-severe endometriosis. The strongest association signal was on 7p15.2 (rs12700667) for ‘all’ endometriosis (P = 2.6 × 10−7, OR = 1.22 (1.13-1.32)) and for moderate-severe disease (P = 1.5 × 10−9 (OR = 1.38 (1.24-1.53)). We replicated rs12700667 in an independent US cohort of 2,392 self-reported surgically confirmed endometriosis cases and 2,271 controls (P = 1.2 × 10−3, OR = 1.17 (1.06-1.28)), resulting in a genome-wide significant P-value of 1.4 × 10−9 (OR = 1.20 (1.13-1.27)) for ‘all’ endometriosis in our combined datasets of 5,586 cases and 9,331 controls. SNP rs12700667 is located in an inter-genic region upstream of plausible candidate genes NFE2L3 and HOXA10.
doi:10.1038/ng.731
PMCID: PMC3019124  PMID: 21151130
24.  Association between psychosocial factors and pain in patients with trigger finger 
Purpose
To test the hypothesis that psychological factors correlate with pain intensity in trigger finger (TF).
Methods
Patients with TF were selected from two previous cohort studies measuring pain intensity and psychological parameters, 82 from one study and 72 from another. Correlation testing and multiple linear regression was performed. Measures included the pain catastrophizing scale (PCS), pain self-efficacy questionnaire (PSEQ), patient health questionnaire depression (PHQ-D) scale, center for epidemiologic studies depression (CES-D) scale, pain anxiety symptoms score (PASS), and the eysenck personality questionnaire (EPQ-R) scales.
Results
There was moderate correlation between pain intensity and PCS (ρ = 0.52; P < 0.001) and PSEQ (ρ = − 0.36; P < 0.001). There was weak correlation between pain and PHQ-D (ρ = 0.23; P = 0.019). No significant correlation existed with CES-D or EPQ-R. PCS accounted for 26% of the variance in pain for patients awaiting surgery (P < 0.001).
Conclusion
Self-reported pain in TF has moderate correlation with psychological factors, most predominantly pain catastrophizing.
doi:10.1007/s12593-010-0009-4
PMCID: PMC3452976  PMID: 23129948
25.  Transactional Sex among Youths in Post-conflict Liberia 
This paper presents findings on sexual risk behaviours of Liberian youths based on five focus-group discussions conducted with 6th and 7th graders (n=36) attending an elementary/middle school in Monrovia, Liberia. The purpose of the focus-group discussions was to gain an understanding of the sexual behaviours of in-school Liberian adolescents. The focus-group discussions were part of a larger study to adapt an evi-dence-based HIV-prevention intervention—Making Proud Choices!—for in-school youths. Post-conflict conditions were discussed as a contributor to the emergence of high-risk sexual behaviours, including transactional sex, sexual violence, and lack of condom-use. Transactional sex was often described by the focus-group participants as occurring between young females and older, more financially-secure males to obtain cash, food, clothing, western commodities, and school-fees and was often encouraged by parents and promoted by peers. The findings also indicate that female adolescents make choices to engage in transactional sex to gain access to a continuum of material and consumer needs. These findings suggest that individual risk-taking behaviours are nested within complex sexual economies and that HIV-prevention interventions should be considered that leverage females’ agency and control.
PMCID: PMC3126983  PMID: 21608420
Acquired immunodeficiency syndrome; HIV; Sex behaviour; Transactional sex; Youth; Liberia

Results 1-25 (40)