A validated normative model for human uterine volume from birth to age 40 years

Transabdominal pelvic ultrasound and/or pelvic Magnetic Resonance Imaging are safe, accurate and non - invasive means of determining the size and configuration of the internal female genitalia. The assessment of uterine size and volume is helpful in the assessment of many conditions including disorders of sex development, precocious or delayed puberty, infertility and menstrual disorders. Using our own data from the assessment of MRI scans in healthy young females and data extracted from four studies that assessed uterine volume using transabdominal ultrasound in healthy females we have derived and validated a normative model of uterine volume from birth to age 40 years. This shows that uterine volume increases across childhood, with a faster increase in adolescence reflecting the influence of puberty, followed by a slow but progressive rise during adult life. The model suggests that around 84% of the variation in uterine volumes in the healthy population up to age 40 is due to age alone . The derivation of a validated normative model for uterine volume from birth to age 40 years has important clinical applications by providing age-related reference values for uterine volume.Publisher PDFPeer reviewe

An externally validated age-related model of mean follicle density in the cortex of the human ovary

The population of non-growing follicles present in the ovary is defined as the ovarian reserve. This underpins the reproductive lifespan in women, with its depletion determining age at loss of fertility and the menopause. Data amassed from published results of indirect invasive and non-invasive procedures has resulted in the generation of predictive models which estimate the ovarian reserve from conception throughout adult life. The distribution of follicles in the ovary is not uniform, with the great majority of NGFs located in the cortex, which is the region normally biopsied and used for fertility preservation. Previous models have however analysed whole ovary NGF populations and ovarian volumes, but not cortical NGF density. In this study we compared mean non-growing follicle density values obtained from tissue samples from 13 ovarian cortical biopsies (16-37 years) against age- matched model-predicted values generated from population and ovarian volume models, taking into account the proportion of the ovary that is cortex. A mean non-growing follicle density was calculated for each patient by counting all follicles in a given volume of freshly biopsied ovarian cortical tissue. These values were compared to age-matched model generated densities and the correlation between data sets tested. Non-growing follicle density values obtained from fresh biopsied ovarian cortex samples closely matched model generated data with low mean difference, tight agreement limits and no proportional error between the observed and predicted results. These findings validate the use of the population and ovarian volume models to accurately predict mean follicle density in the ovarian cortex of adult women.Publisher PDFPeer reviewe

Anti-müllerian hormone is not associated with cardiometabolic risk factors in adolescent females

<p>Objectives: Epidemiological evidence for associations of Anti-Müllerian hormone (AMH) with cardiometabolic risk factors is lacking. Existing evidence comes from small studies in select adult populations, and findings are conflicting. We aimed to assess whether AMH is associated with cardiometabolic risk factors in a general population of adolescent females.</p> <p>Methods: AMH, fasting insulin, glucose, HDLc, LDLc, triglycerides and C-reactive protein (CRP) were measured at a mean age 15.5 years in 1,308 female participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Multivariable linear regression was used to examine associations of AMH with these cardiometabolic outcomes.</p> <p>Results: AMH values ranged from 0.16–35.84 ng/ml and median AMH was 3.57 ng/ml (IQR: 2.41, 5.49). For females classified as post-pubertal (n = 848) at the time of assessment median (IQR) AMH was 3.81 ng/ml (2.55, 5.82) compared with 3.25 ng/ml (2.23, 5.05) in those classed as early pubertal (n = 460, P≤0.001). After adjusting for birth weight, gestational age, pubertal stage, age, ethnicity, socioeconomic position, adiposity and use of hormonal contraceptives, there were no associations with any of the cardiometabolic outcomes. For example fasting insulin changed by 0% per doubling of AMH (95%CI: −3%,+2%) p = 0.70, with identical results if HOMA-IR was used. Results were similar after additional adjustment for smoking, physical activity and age at menarche, after exclusion of 3% of females with the highest AMH values, after excluding those that had not started menarche and after excluding those using hormonal contraceptives.</p> <p>Conclusion: Our results suggest that in healthy adolescent females, AMH is not associated with cardiometabolic risk factors.</p&gt

A Normative Model of Serum Inhibin B in Young Males

RTM is supported by a Wellcome Trust Intermediate Clinical Fellowship (Grant No: 098522).Inhibin B has been identified as a potential marker of Sertoli cell function in males. The aim of this study is to produce a normative model of serum inhibin B in males from birth to seventeen years. We used a well-defined search strategy to identify studies containing data that can contribute to a larger approximation of the healthy population. We combined data from four published studies (n = 709) and derived an internally validated model with high goodness-of-fit and normally distributed residuals. Our results show that inhibin B increases following birth to a post-natal peak of 270 pg/mL (IQR 210–335 pg/mL) and then decreases during childhood followed by a rise at around 8 years, peaking at a mean 305 pg/mL (IQR 240–445 pg/mL) at around age 17. Following this peak there is a slow decline to the standard mature adult normal range of 170 pg/mL (IQR 125–215 pg/mL). This normative model suggests that 35% of the variation in Inhibin B levels in young males is due to age alone, provides an age-specific reference range for inhibin B in the young healthy male population, and will be a powerful tool in evaluating the potential of inhibin B as a marker of Sertoli cell function in pre-pubertal boys.Publisher PDFPeer reviewe

Is health-related quality of life associated with the risk of low-energy wrist fracture: a case-control study

<p>Abstract</p> <p>Background</p> <p>Some risk factors for low-energy wrist fracture have been identified. However, self-reported measures such as health-related quality of life (HRQOL) have not been examined as potential risk factors for wrist fracture. The aims of this study were to compare HRQOL prior to a low-energy wrist fracture in elderly patients (≥ 50 years) with HRQOL in age- and sex-matched controls, and to explore the association between HRQOL and wrist fracture after adjusting for known risk factors for fracture such as age, weight, osteoporosis and falls.</p> <p>Methods</p> <p>Patients with a low-energy wrist fracture (n = 181) and age- and sex-matched controls (n = 181) were studied. Shortly after fracture (median 10 days), patients assessed their HRQOL before fracture using the Short Form 36 (SF-36). Statistical tests included <it>t </it>tests and multivariate logistic regression analysis.</p> <p>Results</p> <p>Several dimensions of HRQOL were significantly associated with wrist fracture. The direction of the associations with wrist fracture varied between the different sub-dimensions of the SF-36. After controlling for demographic and clinical variables, higher scores on <it>general health </it>(odds ratio (OR) = 1.31, 95% confidence interval (CI) = 1.10–1.56), <it>bodily pain </it>(OR = 1.18, 95% CI = 1.03–1.34) and <it>mental health </it>(OR = 1.39, 95% CI = 1.09–1.79) were related to an increased chance of being a wrist fracture patient rather than a control. In contrast, higher scores on <it>physical role limitation </it>(OR = 0.87, 95% CI = 0.79–0.95) and <it>social function </it>(OR = 0.65, 95% CI 0.53–0.80) decreased this chance. Significant associations with wrist fracture were also found for living alone (OR = 1.91, 95% CI 1.07–3.4), low body mass index (BMI) (OR = 0.92, 95% CI 0.86–0.98), osteoporosis (OR = 3.30, 95% CI 1.67–6.50) and previous falls (OR = 2.01, 95% CI 1.16–3.49).</p> <p>Conclusion</p> <p>Wrist fracture patients perceive themselves to be as healthy as the controls before fracture. Our data indicate that patients with favourable and unfavourable HRQOL measures may be at increased risk of wrist fracture.</p

Follicle Stimulating Hormone is an accurate predictor of azoospermia in childhood cancer survivors

Funding: RTM is supported by a Wellcome Trust Intermediate Clinical Fellowship (grant no: 098522), https://wellcome.ac.uk/what-we-do/directories/intermediate-clinical-fellowships-people-funded. TWK is supported by Engineering and Physical Sciences Research Council grant EP/P015638/1, http://gow.epsrc.ac.uk/NGBOViewGrant.aspx?GrantRef=EP/P015638/1.The accuracy of Follicle Stimulating Hormone as a predictor of azoospermia in adult survivors of childhood cancer is unclear, with conflicting results in the published literature. A systematic review and post hoc analysis of combined data (n = 367) were performed on all published studies containing extractable data on both serum Follicle Stimulating Hormone concentration and semen concentration in survivors of childhood cancer. PubMed and Medline databases were searched up to March 2017 by two blind investigators. Articles were included if they contained both serum FSH concentration and semen concentration, used World Health Organisation certified methods for semen analysis, and the study participants were all childhood cancer survivors. There was no evidence for either publication bias or heterogeneity for the five studies. For the combined data (n = 367) the optimal Follicle Stimulating Hormone threshold was 10.4 IU/L with specificity 81% (95% CI 76%–86%) and sensitivity 83% (95% CI 76%–89%). The AUC was 0.89 (95%CI 0.86–0.93). A range of threshold FSH values for the diagnosis of azoospermia with their associated sensitivities and specificities were calculated. This study provides strong supporting evidence for the use of serum Follicle Stimulating Hormone as a surrogate biomarker for azoospermia in adult males who have been treated for childhood cancer.Publisher PDFPeer reviewe

Qualitative modelling via constraint programming

Qualitative modelling is a technique integrating the fields of theoretical computer science, artificial intelligence and the physical and biological sciences. The aim is to be able to model the behaviour of systems without estimating parameter values and fixing the exact quantitative dynamics. Traditional applications are the study of the dynamics of physical and biological systems at a higher level of abstraction than that obtained by estimation of numerical parameter values for a fixed quantitative model. Qualitative modelling has been studied and implemented to varying degrees of sophistication in Petri nets, process calculi and constraint programming. In this paper we reflect on the strengths and weaknesses of existing frameworks, we demonstrate how recent advances in constraint programming can be leveraged to produce high quality qualitative models, and we describe the advances in theory and technology that would be needed to make constraint programming the best option for scientific investigation in the broadest sense

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Emotional well-being in children and adolescents treated with atomoxetine for attention-deficit/hyperactivity disorder: Findings from a patient, parent and physician perspective using items from the pediatric adverse event rating scale (PAERS)

<p>Abstract</p> <p>Background</p> <p>The objective of this analysis was to measure changes in items on the Pediatric Adverse Event Rating Scale (PAERS) that relate to emotional well-being of children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD) during treatment with atomoxetine for up to 24 weeks from the perspective of the patient, the parent, and the physician.</p> <p>Methods</p> <p>Patients aged 6–17 years with ADHD were treated with atomoxetine (target dose 1.2 mg/kg/day). In the two studies on which this secondary analysis is based the PAERS was used to assess the tolerability of atomoxetine in children and adolescents. This scale has a total of 48 items. The ten items that reflect emotional well-being were selected to measure changes over time from a patient, parent, and physician perspective.</p> <p>Results</p> <p>421 patients were treated with atomoxetine. 355 patients completed the 8-week treatment period, and 260 patients completed the 24-week treatment period. The ten items that reflect emotional well-being were grouped in five dimensions: depressed mood, self-harm, irritability/agitation, drowsiness, and euphoria. The scores of these dimensions decreased over time, both from a patient as well as from a parent and physician perspective. Only the dimension self-harm was extremely low at baseline and stayed low over time. The mean scores for the ten items depended on the rater perspective.</p> <p>Conclusion</p> <p>The emotional well-being of children and adolescents with ADHD improved in terms of depressed mood, irritability/agitation, drowsiness, and euphoria during treatment with atomoxetine for up to 24 weeks.</p