Search

BACKGROUND: The menopausal transition (MT) is a biological inevitability for all ageing women that can be associated with changes in mood, including depressive symptoms. There is tentative evidence that women who develop depression during the MT have greater risk of subsequent depressive episodes, as well as increased health morbidity and mortality. Thus, preventing depression during the MT could enhance both current and the future health and well-being of women. This study aims to test the efficacy of a client-centred health promotion intervention to decrease the 12-month incidence of clinically significant symptoms of depression among women undergoing the MT. METHODS/DESIGN: This randomised controlled trial will recruit 300 women undergoing the MT living in the Perth metropolitan area. They will be free of clinically significant symptoms of depression and of psychotic or bipolar disorders. Consenting participants will be stratified for the presence of subsyndromal symptoms of depression and then randomly assigned to the intervention or control group. The intervention will consist of eight telephone health promotion sessions that will provide training in problem solving and education about the MT, healthy ageing, depression and anxiety, and management of chronic health symptoms and problems. The primary outcome of interest is the onset of a major depressive episode according the DSM-IV-TR criteria during the 12-month follow-up or of clinically significant symptoms of depression, as established by a score of 15 or greater on the Patient Health Questionnaire (PHQ-9). Secondary outcomes of interest include changes in the severity of symptoms of depression and anxiety (Hospital Anxiety and Depression Scale, HADS), quality of life (Short Form Health Survey, SF-12), and lifestyle. DISCUSSION: Current evidence shows that depressive symptoms and disorders are leading causes of disability worldwide, and that they are relatively common during the MT. This study will use a mu

OBJECTIVE: After cancer treatment, troublesome menopausal symptoms are common but poorly understood. Using standardized instruments, we measured differences in symptom nature, severity, impact on quality of life, and sexual function between cancer survivors and noncancer participants. METHODS: The Menopause Symptoms After Cancer Clinic operates within the general menopause service in a large women's hospital, providing menopause advice and management to women with menopausal symptoms and a cancer history. Menopausal symptoms were recorded using the Greene Climacteric Scale, past-week symptoms were recorded using the Functional Assessment of Cancer Therapy breast cancer subscale and endocrine symptom subscale, and sexual symptoms were recorded using Fallowfield's Sexual Activity Questionnaire. RESULTS: Cancer survivors (n = 934) and noncancer participants (n = 155) did not significantly differ by age at menopause (46 y) or age at first clinic visit (51 y). Cancer survivors were more likely than noncancer participants to be severely troubled by vasomotor symptoms (hot flushes and night sweats; odds ratio, 1.71; 95% CI, 1.06-2.74) and reported more frequent (6.0 vs 3.1 in 24 h; P < 0.001) and more severe (P = 0.008) hot flushes. In contrast, cancer survivors were significantly less troubled by psychological and somatic symptoms and reported better quality of life than noncancer participants. Groups did not differ significantly in physical or functional well-being, gynecologic symptom severity, or sexual function. CONCLUSIONS: Cancer survivors are more troubled by vasomotor symptoms than noncancer participants, but noncancer participants report greater psychological symptoms. Sexual function does not differ. An improved understanding of the nature and impact of menopause on cancer survivors can be used to direct management protocols.

Accurately measuring hormone exposure during prenatal life presents a methodological challenge and there is currently no "gold standard" approach. Ideally, circulating fetal hormone levels would be measured at repeated time points during pregnancy. However, it is not currently possible to obtain fetal blood samples without significant risk to the fetus, and therefore surrogate markers of fetal hormone levels must be utilized. Umbilical cord blood can be readily obtained at birth and largely reflects fetal circulation in late gestation. This review examines the accuracy and biological interpretation of the measurement of androgens and estrogens in cord blood. The use of cord blood hormones to understand and investigate human development is then discussed.

Accurately measuring hormone exposure during prenatal life presents a methodological challenge and there is currently no “gold standard” approach. Ideally, circulating fetal hormone levels would be measured at repeated time points during pregnancy. However, it is not currently possible to obtain fetal blood samples without significant risk to the fetus, and therefore surrogate markers of fetal hormone levels must be utilized. Umbilical cord blood can be readily obtained at birth and largely reflects fetal circulation in late gestation.This review examines the accuracy and biological interpretation of the measurement of androgens and estrogens in cord blood. The use of cord blood hormones to understand and investigate human development is then discussed.

We use a nonlinear, fully compressible, two-dimensional numerical model to study the effects of dissipation on gravity wave packet spectra in the thermosphere. Numerical simulations are performed to excite gravity wave packets using either a time-dependent vertical body forcing at the bottom boundary or a specified initial wave perturbation. Three simulation case studies are performed to excite (1) a steady state monochromatic wave, (2) a spectrally broad wave packet, and (3) a quasi-monochromatic wave packet. In addition, we analyze (4) an initial condition simulation with an isothermal background. We find that, in cases where the wave is not continually forced, the dominant vertical wavelength decreases in time, predominantly due to a combination of refraction from the thermosphere and dissipation of the packets’ high frequency components as they quickly reach high altitude. In the continually forced steady state case, the dominant vertical wavelength remains constant once initial transients have passed. The vertical wavelength in all simulations increases with altitude above the dissipation altitude (the point at which dissipation effects are greater than the wave amplitude growth caused by decreasing background density) at any fixed time. However, a shift to smaller vertical wavelength values in time is clearly exhibited as high-frequency, long vertical wavelength components reach high altitudes and dissipate first, to be replaced by slower waves of shorter vertical wavelength. Results suggest that the dispersion of a packet significantly determines its spectral evolution in the dissipative thermosphere.

Abundant short‒period, small‒scale gravity waves have been identified in the mesosphere and lower thermosphere over Halley, Antarctica, via ground‒based airglow image data. Although many are observed as freely propagating at the heights of the airglow layers, new results under modeled conditions reveal that a significant fraction of these waves may be subject to reflections at altitudes above and below. The waves may at times be trapped within broad thermal ducts, spanning from the tropopause or stratopause to the base of the thermosphere (∼140 km), which may facilitate long‒range propagation (∼1000s of km) under favorable wind conditions.

In contrast to many capillary beds, the glomerulus supports leukocyte recruitment during inflammation. However, the behaviour of leukocytes after their recruitment to the glomerulus is unknown. In this study, we used multiphoton microscopy to examine leukocyte behaviour in the glomerular microvasculature under steady-state and inflamed conditions. In uninflamed glomeruli, neutrophils and monocytes were retained within capillaries for several minutes, during which time leukocytes were either static or migrated. Inflammation increased the duration of leukocyte retention, an effect that was eliminated via inhibition of Mac-1. In addition, both static and migratory neutrophils generated oxidants in inflamed glomeruli. This work establishes a new paradigm for glomerular inflammation, showing that acute inflammation does not induce leukocyte recruitment per se, instead increasing the duration of leukocyte retention in the glomerulus, during which time leukocytes adopt either static or migratory behaviors. These findings describe a novel form of multicellular intravascular patrolling that may contribute to the susceptibility of the glomerulus to inflammation.

Despite the prevalence of uterine fibroids (Fs), few studies have investigated the links between clinical features and the cellular or molecular mechanisms that drive F growth and development. Such knowledge will ultimately help to differentiate symptomatic from asymptomatic Fs and could result in the development of more effective and individualized treatments. The aim of this study was to investigate the relationship between ultrasound appearance, blood flow, and angiogenic gene expression in F, perifibroid (PM), and distant myometrial (DM) tissues. We hypothesized that angiogenic gene expression would be increased in tissues and participants that showed increased blood flow by Doppler ultrasound. The study was performed using Doppler ultrasound to measure blood flow prior to hysterectomy, with subsequent tissue samples from the F, PM, and DM being investigated for angiogenic gene expression. Overall, PM blood flow (measured as peak systolic velocity [PSV]) was higher than F blood flow, although significant heterogeneity was seen in vascularity and blood flow between different Fs and their surrounding myometrium. We did not find any correlation between PSV and any other clinical or molecular parameter in this study. We identified 19 angiogenesis pathway-related genes with significant differences in expression between F and DM, and 2 genes, matrix metalloproteinase 9 (MMP9) and Neuropilin 2 (NRP2), that were significantly different between F and PM. These results are consistent with subtle differences between PM and DM. Understanding the differences between symptomatic versus asymptomatic Fs may eventually lead to more effective treatments that directly target the source of heavy menstrual bleeding. © 2013 The Author(s).

Antenatal testosterone exposure influences fetal neurodevelopment and gender-role behavior in postnatal life and may contribute to differences in developmental psychopathology during childhood. We prospectively measured the associations between umbilical cord blood testosterone levels at birth and childhood behavioral development in both males and females from a large population based sample. The study comprised 430 females and 429 males from the Western Australian Pregnancy Cohort (Raine) Study where umbilical cord blood had been collected. Total testosterone concentrations were determined by mass spectrometry and bioavailable testosterone (BioT) levels were calculated. At two, five, eight and ten years of age, the participants completed the Child Behavior Checklist (CBCL). Linear regression models were used to analyse the relationship between BioT concentrations (in quartiles) and CBCL scores (total, internalizing, externalizing and selected syndrome). Boys had higher mean CBCL T-scores than girls across all ages of follow-up. There was no significant relationship between cord blood BioT quartiles and CBCL total, internalizing and externalizing T-scores at age two or five to ten combined. In the syndrome score analyses, higher BioT quartiles were associated with significantly lower scores for attention problems for boys at age five, eight and ten, and greater withdrawal symptoms in pre-school girls (age five). We did not identify a consistent relationship between antenatal testosterone exposure and total, internalizing or externalizing behavioral difficulties in childhood. Higher umbilical cord BioT levels were associated with lower scores for attention problems in boys up to 10 years and more withdrawn behavior in 5-year-old girls; however, these findings were not consistent across ages and require further investigation in a larger sample.

OBJECTIVE: Younger age at menarche (AAM) may put girls at risk for earlier first sexual intercourse (FSI). Young age at FSI has far-reaching negative outcomes. We describe the longitudinal relationship between AAM and FSI in a large prospective birth cohort. METHODS: AAM was collected from 554 girls from the Western Australia (Raine) Pregnancy Cohort Study, prospectively from age 10 or retrospectively at age 14. Age at FSI was collected at ages 17 and 20. Cox regression models describe likelihood of FSI by age and years since menarche for younger (<12 years) and older (≥14 years) AAM relative to average AAM (12-13 years). RESULTS: Girls with younger AAM and average AAM were equally likely to have FSI by age 16 (adjusted hazard ratio [aHR]: 0.90 [95% confidence interval (CI): 0.60-1.35]). FSI by age 16 was less likely among girls with older AAM than those with average AAM (aHR: 0.35 [95% CI: 0.17-0.72]). Girls with younger AAM had a longer median interval between menarche and FSI than girls with average AAM (5.0 years [interquartile range: 4.4-8.5 years] vs 3.7 years [interquartile range: 2.4-5.3 years]). Those with younger AAM were less likely to report FSI within 4 years of menarche than those with average AAM (0-2 years aHR: 0.04 [95% CI: 0.01-0.31]; 2-4 years aHR: 0.36 [95% CI: 0.23-0.55]). By age 20, 429 girls (77.4%) reported FSI. CONCLUSIONS: Younger AAM was not a risk factor for younger age at FSI in this cohort.

Abundant short-period, small-scale gravity waves have been identified in the mesosphere and lower thermosphere over Halley, Antarctica, via ground-based airglow image data. Although many are observed as freely propagating at the heights of the airglow layers, new results under modeled conditions reveal that a significant fraction of these waves may be subject to reflections at altitudes above and below.The waves may at times be trapped within broad thermal ducts, spanning from the tropopause or stratopause to the base of the thermosphere (~140 km), which may facilitate long-range propagation (~1000s of km) under favorable wind conditions.

BACKGROUND: Increased prenatal testosterone exposure has been hypothesized as a mechanism underlying autism spectrum disorders (ASD). However, no studies have prospectively measured prenatal testosterone exposure and ASD. The current study sought to determine whether testosterone concentrations in umbilical cord blood are associated with a clinical diagnosis of ASD in a small number of children and with autistic-like traits in the general population. METHODS: Umbilical cord blood was collected from 707 children. Samples were analyzed for total (TT) and bioavailable (BioT) testosterone concentrations. Parent report indicated that five individuals had a clinical diagnosis of ASD. Those participants without a diagnosis were approached in early adulthood to complete the Autism-Spectrum Quotient (AQ), a self-report measure of autistic-like traits, with 184 males (M = 20.10 years; SD= 0.65 years) and 190 females (M = 19.92 years; SD=0.68 years) providing data. RESULTS: The BioT and TT concentrations of the five children diagnosed with ASD were within one standard-deviation of the sex-specific means. Spearman's rank-order coefficients revealed no significant correlations between TT levels and scores on any AQ scale among males (rho range: -.01 to .06) or females (rho value range: -.07 to .01). There was also no significant association between BioT or TT concentrations and AQ scores among males (rho value range: -.07 to .08) or females (rho value range: -.06 to .12). Males were more likely than females to have 'high' scores (upper decile) on the AQ scale relating pattern and detail processing. However, the likelihood of a high score on this scale was unrelated to BioT and TT concentrations in both males and females. CONCLUSIONS: These findings indicate that testosterone concentrations from umbilical cord blood are unrelated to autistic-like traits in the general population. However, the findings do not exclude an association between testosterone exposure in early intrauteri

Erratic, "unscheduled", vaginal bleeding continues to be the greatest disadvantage associated with widespread use of long-acting, progestogen-only methods of contraception. As a consequence, it is also the main reason for premature discontinuation of use of these methods in most cultures. From other perspectives, these methods have high acceptability, very high contraceptive efficacy and a range of valuable, added, non-contraceptive health benefits. There has been widespread awareness of the variability of these vaginal bleeding patterns associated with long-acting methods for several decades and much research has been invested into studying their patterns and implications. Considerable research has also been directed towards trying to understand the underlying mechanisms responsible for the unpredictable bleeding. Much has been clarified about the multiple mechanisms contributing to the appearance of superficial, thin-walled fragile vessels within the endometrium of many of those women with troublesome bleeding, but there is still little understanding of why some women develop these vessels and others have no fragile vessels (and may therefore develop amenorrhea). We now have several medical approaches to reliably stopping a prolonged episode of troublesome bleeding, but no good therapy to produce long-lasting relief from recurrence of erratic bleeding in predisposed women. Future understanding of the variability in individual endometrial responses in different women may be a key to solving this frustrating symptom.

Objective: To characterise fetal brain growth in children with specifi c language impairment (SLI).Design: A nested case–control study. Setting- Perth, Western Australia. Participants - Thirty children meeting criteria for SLI at age 10 years were individually matched with a typically developing comparison child on sex, non-verbal ability, fetal gestational age, maternal age at conception,smoking and alcohol intake during pregnancy. Main outcome measures Occipitofrontalhead circumference (HC) was measured using ultrasonography at approximately 18 weeks gestation.Femur length provided a measure of fetal length. Occipitofrontal HC was measured at birth and at the 1-year postnatal follow-up using a precise paper tape measure, while crown-heel length acted as an index of body length at both time points. Raw data were transformed to z-scores using reference norms.

Recent advances in GPS data processing have demonstrated that ground-based GPS receivers are capable of detecting ionospheric TEC perturbations caused by surface-generated Rayleigh, acoustic and gravity waves. There have been a number of publications discussing TEC perturbations immediately following the M 9.0 Tohoku earthquake in Japan on March 11, 2011. Most investigators have focused on the ionospheric responses up to a few hours following the earthquake and tsunami. In our research, in addition to March 11, 2011 we investigate global ionospheric TEC perturbations a day before and after the event. We also compare indices of geomagnetic activity on all three days with perturbations in TEC, revealing strong geomagnetic storm conditions that are also apparent in processed GEONET TEC observations. In addition to the traveling ionospheric disturbances (TIDs)produced by the earthquake and tsunami, we also detect “regular” TIDs across Japan about 5 hours following the Tohoku event, concluding these are likely due to geomagnetic activity. The variety of observed TEC perturbations are consistent with tsunami-generated gravity waves, auroral activity, regular TIDs and equatorial fluctuations induced by increased geomagnetic activity. We demonstrate our capabilities to monitor TEC fluctuations using JPL’s real-time Global Assimilative Ionospheric Model (GAIM) system. We show that a real-time global TEC monitoring network is able to detect the acoustic and gravity waves generated by the earthquake and tsunami. With additional real-time stations deployed, this new capability has the potential to provide real-time monitoring of TEC perturbations that could potentially serve as a plug-in to enhance existing early warning systems.

The reasons why some fi broids cause heavy menstrual bleeding (HMB) are unknown. Many fi broids having a highly vascular plexus in the peri-fi broid myometrium (PFM), however, the potential role of the PFM in HMB has never been investigated. The aim of this study was to correlate clinical symptoms, Doppler ultrasound appearances and tissue gene expression profi les in women scheduled for hysterectomy due to symptomatic fi broids. We hypothesised that fi broid heterogeneity, colour fl ow and spectral Doppler resistance indices would correlate with differences in gene expression profi les. We further hypothesised that increased peri-fi broid gene expression of key angiogenic genes would correlate with increased peri-fi broid vascularity. N=6 patients underwent B-mode, colour and spectral Doppler ultrasound assessment. Following hysterectomy tissue samples collected from three areas - fi broid, PFM and distant myometrium (DM) were analysed using quantitative RT-PCR and angiogenesis PCR array. A higher mean peak systolic velocity (PSV) in the PFM region when compared to mean PSV within the fi broid (p<0.001) was seen. Differences in angiogenic gene expression were consistent with the heterogeneity of the clinical data collected. Fibroid heterogeneity within a single uterus was also demonstrated. Fibroid samples from the same uterus clustered separately based on their gene expression, and had different blood fl ow profi les in 3 out of 4 patients with multiple fi broids. Signifi cant differences in gene expression between tissues included: S1PR1, EFNA3 and SERPINF1 which were differentially expressed between F and both PFM and DM; EGF, FGF1 and MMP9 between F and PFM; KDR, NRP2 and MMP2 between F and DM; and FGF2 between DM and other groups. Gene interaction networks identifi ed differences between fi broid and PFM regions compared to fi broid versus DM. This is the fi rst attempt to correlate fi broid blood fl ow and clinical symptoms with gene expression, and has obtai

Understanding of the mechanisms that cause fibroid associated heavy menstrual bleeding (HMB) is limited. Despite many fibroids having a highly vascular peri-fibroid myometrial (PFM) zone, angiogenic gene expression in this area has never been investigated. The aim of this study was to correlate clinical symptoms, ultrasound appearances and tissue gene expression profiles in women scheduled for hysterectomy due to symptomatic fibroids. We hypothesised that fibroid heterogeneity, colour flow and spectral Doppler resistive indices would correlate with differences in gene expression profiles. It was thought and that increased peri-fibroid gene expression of key angiogenic genes would correlate with increased peri-fibroid vascularity. N=6 patients underwent B-mode, colour and spectral Doppler ultrasound assessment. Following hysterectomy tissue samples collected from three areas - fibroid, PFM and distant myometrium (DM) were analysed using quantitative RT-PCR and a customised angiogenesis PCR array. A higher mean peak systolic velocity (PSV) in the PFM region when compared to mean PSV within the fibroid (P < 0.001) was seen. Differences in angiogenic gene expression were consistent with the heterogeneity of the clinical data collected. One fibroid sample showed dissimilar gene expression to all other fibroids; at ultrasound and sample collection significant degenerative features were observed. Fibroid heterogeneity within a single uterus was also demonstrated, with two fibroids from the one uterus having significantly dissimilar gene profiles and ultrasound appearances. No differences in gene expression were found between PFM and DM. Despite this, gene interaction maps showed different interaction of genes between fibroid and PFM regions compared to genes between the fibroid and the DM. These are the first molecular data demonstrating that the PFM region may be functionally distinct from distant myometrium.

There is accumulating evidence that autistic traits (AT) are on a continuum in the general population, with clinical autism representing the extreme end of a quantitative distribution. While the nature and severity of symptoms in clinical autism are known to persist over time, no study has examined the long-term stability of AT among typically developing toddlers. The current investigation measured AT in 360 males and 400 males from the general population close to two decades apart, using the Pervasive Developmental Disorder subscale of the Child Behavior Checklist in early childhood (M = 2.14 years; SD = 0.15), and the Autism-Spectrum Quotient in early adulthood (M = 19.50 years; SD = 0.70). Items from each scale were further divided into social (difficulties with social interaction and communication) and non-social (restricted and repetitive behaviours and interests) AT. The association between child and adult measurements of AT as well the influence of potentially confounding sociodemographic, antenatal and obstetric variables were assessed using Pearson's correlations and linear regression. For males, Total AT in early childhood were positively correlated with total AT (r = .16, p = .002) and social AT (r = .16, p = .002) in adulthood. There was also a positive correlation for males between social AT measured in early childhood and Total (r = .17, p = .001) and social AT (r = .16, p = .002) measured in adulthood. Correlations for non-social AT did not achieve significance in males. Furthermore, there was no significant longitudinal association in AT observed for males or females. Despite the constraints of using different measures and different raters at the two ages, this study found modest developmental stability of social AT from early childhood to adulthood in boys.

Continuous combined hormone therapy (HT) is effective for menopausal vasomotor symptoms and vaginal dryness but commonly leads to unscheduled vaginal bleeding and spotting. Unscheduled bleeding is disliked by women and may lead to invasive investigations to exclude underlying pelvic pathology. In most cases investigations do not reveal any underlying cause for the bleeding.

PURPOSE: For many young women with early breast cancer, fertility is a priority. Interventions to retain fertility options generally need to be accessed before chemotherapy, but many women do not receive information regarding these options in a timely fashion. Knowledge about fertility and decisional conflict has not previously been measured in young patients with breast cancer considering future pregnancies. METHODS: One hundred eleven young women with early breast cancer who had not yet completed their families were recruited around the time of diagnosis. Knowledge regarding fertility-related information, decisional conflict, and preferences regarding fertility information and decision making was measured. RESULTS: From a potential fertility-related knowledge score of 10, the mean was 5.2 (standard deviation = 2.3; range, 0 to 10). Decreased knowledge was associated with increased decisional conflict about pursuing fertility preserving interventions (odds ratio [OR] = 0.57; 95% CI, 0.44 to 0.73; P < .001). Thirty-one percent of women reported that they would consider undertaking in vitro fertilization (IVF) as a method to conserve their fertility, whereas 38% were uncertain. Consideration of IVF was not related to whether subjects were in a committed relationship (OR = 1.20; P = .716) or a definite desire for more children (OR = 1.54; P = .513). CONCLUSION: Around diagnosis, many young patients with breast cancer have low levels of knowledge about fertility issues. Further, low knowledge is associated with increased decisional conflict, which is likely to undermine the quality of decision making. These findings suggest that targeted and timely fertility information may reduce decisional conflict and increase informed choice. Neither relationship status nor firm plans regarding future children reliably predict desire to pursue fertility preservation.

BACKGROUND: Diagnosing polycystic ovary syndrome (PCOS) in adolescence is clinically challenging. The prevalence of clinical, ultrasound and biochemical features of PCOS in a community-based adolescent population using current diagnostic criteria has not previously been described. Methods This was a prospective cohort study with 244 unselected post-menarchal girls, mean age 15.2 years, of whom 91% were Caucasian. Subjects were recruited from a large population-based birth cohort (the Raine cohort). Clinical hyperandrogenism (HA) was quantified using Ferriman-Gallwey scores. In the early follicular phase (Day 2-6), we measured circulating androgens and sex hormone-binding globulin by immunoassay, and ovarian morphology was assessed by transabdominal ultrasound examination. BMI and waisthip ratio were measured. Results Normal ranges for early follicular phase androgens in adolescence were derived for this population. The top 5 and 10% of circulating free testosterone levels were 45.6 and 34.5 pmol/l, respectively. Fifty-one percent of girls reported menstrual irregularity. Clinical HA was uncommon, being observed in only 3.5% of girls. Mean ovarian volume was greater than that reported by others in adult women and 35% of girls had polycystic ovary morphology on transabdominal ultrasound. Taking the upper 5% of free testosterone as HA, 42 girls (18.5%) would have met the Rotterdam criteria for PCOS, 11 girls (5%) the Androgen Excess Society criteria and 7 girls (3.1%) the National Institutes of Health criteria. CONCLUSIONS Menstrual irregularity is common in adolescence and does not relate to clinical or biochemical HA. Diagnostic criteria for PCOS which include ovarian volume and morphology may be of limited use in adolescence. © The Author 2011. Published by Oxford Universi ty Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.