OBJECTIVE: The natural history of nonfunctioning pituitary macroadenomas (NFPMA) after surgical resection is variable, with guidelines unable to define the duration of radiological follow-up. In this first Australian series, we identify risk factors for regrowth/recurrence of NFPMA to assist with guiding recommendations for long-term follow-up. DESIGN: Retrospective analysis of all radiotherapy-naïve cases with NFPMA resected between 1995 and 2013. PATIENTS: One hundred and twenty-three cases had both ≥2 postoperative scans and ≥12-month follow-up. MEASUREMENTS: Regrowth was defined as any sustained increase in diameter of residual adenoma or recurrence as any new adenoma occurring post complete resection on serial pituitary MRI. RESULTS: Median follow-up time was 48 months (interquartile range [IQR]: 31-86). Overall regrowth/recurrence occurred in 29% (36/123). Regrowth occurred in 40% (30/76) at a median time of 44.5 months (IQR 22-80) compared to recurrence of 12.5% (6/48; P=.003), occurring at a median time of 48 months (IQR 12-96; P=.7). Further treatment was required in 66.7% and 56.7%, respectively (=1.0). Risk factors for regrowth/recurrence by multivariate analysis were presence of residual disease and younger age at presentation. The longest time for regrowth was 168 months (14 years) and recurrence 156 months (13 years). CONCLUSIONS: Presence of postoperative residual adenoma and younger age at presentation are the main predictors of regrowth/recurrence in NFPMA. Long-term serial imaging is required to detect regrowth and recurrence in younger patients and those with residual disease. Most regrowth/recurrences will occur within 10 years of follow-up.

BACKGROUND: In pregnancy, untreated chlamydia infection has been associated with adverse outcomes for both mother and infant. Like most women, pregnant women infected with chlamydia do not report genital symptoms, and are therefore unlikely to be aware of their infection. The aim of this study was to determine the acceptability of screening pregnant women aged 16-25 years for chlamydia as part of routine antenatal care. METHODS: As part of a larger prospective, cross-sectional study of pregnant women aged 16-25 years attending antenatal services across Melbourne, Australia, 100 women were invited to participate in a face-to-face, semi structured interview on the acceptability of screening for chlamydia during pregnancy. Women infected with chlamydia were oversampled (n = 31). RESULTS: Women had low levels of awareness of chlamydia before the test, retained relatively little knowledge after the test and commonly had misconceptions around chlamydia transmission, testing and sequelae. Women indicated a high level of acceptance and support for chlamydia screening, expressing their willingness to undertake whatever care was necessary to ensure the health of their baby. There was a strong preference for urine testing over other methods of specimen collection. Women questioned why testing was not already conducted alongside other antenatal STI screening tests, particularly in view of the risks chlamydia poses to the baby. Women who tested positive for chlamydia had mixed reactions, however, most felt relief and gratitude at having had chlamydia detected and reported high levels of partner support. CONCLUSIONS: Chlamydia screening as part of routine antenatal care was considered highly acceptable among young pregnant women who recognized the benefits of screening and strongly supported its implementation as part of routine antenatal care. The acceptability of screening is important to the uptake of chlamydia screening in future antenatal screening strategies.

BACKGROUND: Young people are disproportionately affected by sexually transmissible infections in Australia but face barriers to accessing sexual health services, including concerns over confidentiality and, for some, geographic remoteness. A possible innovation to increase access to services is the use of telemedicine. METHODS: Young people's (aged 16-24) pre-use views on telephone and webcam consultations for sexual health were investigated through a widely-advertised national online survey in Australia. Descriptive statistics were used to describe the study sample and chi-square, Mann-Whitney U test, or t-tests were used to assess associations. Multinomial logistic regression was used to explore the association between the three-level outcome variable (first preference in person, telephone or webcam, and demographic and behavioural variables); odds ratios and 95%CI were calculated using in person as the reference category. Free text responses were analysed thematically. RESULTS: A total of 662 people completed the questionnaire. Overall, 85% of the sample indicated they would be willing to have an in-person consultation with a doctor, 63% a telephone consultation, and 29% a webcam consultation. Men, respondents with same-sex partners, and respondents reporting three or more partners in the previous year were more willing to have a webcam consultation. Imagining they lived 20 minutes from a doctor, 83% of respondents reported that their first preference would be an in-person consultation with a doctor; if imagining they lived two hours from a doctor, 51% preferred a telephone consultation. The main objections to webcam consultations in the free text responses were privacy and security concerns relating to the possibility of the webcam consultation being recorded, saved, and potentially searchable and retrievable online. CONCLUSIONS: This study is the first we are aware of that seeks the views of young people on telemedicine and access to sexual health services. Although only 29% of respondents were willing to have a webcam consultation, such a service may benefit youth who may not otherwise access a sexual health service. The acceptability of webcam consultations may be increased if medical clinics provide clear and accessible privacy policies ensuring that consultations will not be recorded or saved.

BACKGROUND: Australian surveillance data document higher rates of sexually transmissible infections (STIs) among young Aboriginal people (15-29 years) in remote settings than non-Aboriginal young people. Epidemiological data indicate a substantial number of young Aboriginal people do not test for STIs. Rigorous qualitative research can enhance understanding of these findings. This paper documents socio-ecological factors influencing young Aboriginal people's engagement with clinic-based STI testing in two remote settings in the Northern Territory, Australia. METHODS: In-depth interviews with 35 young Aboriginal men and women aged 16-21 years; thematic analysis examining their perceptions and personal experiences of access to clinic-based STI testing. RESULTS: Findings reveal individual, social and health service level influences on willingness to undertake clinic-based STI testing. Individual level barriers included limited knowledge about asymptomatic STIs, attitudinal barriers against testing for symptomatic STIs, and lack of skills to communicate about STIs with health service staff. Social influences both promoted and inhibited STI testing. In setting 1, local social networks enabled intergenerational learning about sexual health and facilitated accompanied visits to health clinics for young women. In setting 2, however, social connectedness inhibited access to STI testing services. Being seen at clinics was perceived to lead to stigmatisation among peers and fear of reputational damage due to STI-related rumours. Modalities of health service provision both enhanced and inhibited STI testing. In setting 1, outreach strategies by male health workers provided young Aboriginal men with opportunities to learn about sexual health, initiate trusting relationships with clinic staff, and gain access to clinics. In setting 2, barriers were created by the location and visibility of the clinic, appointment procedures, waiting rooms and waiting times. Where inhibitive factors at the individual, social and health service levels exist, young Aboriginal people reported more limited access to STI testing. CONCLUSIONS: This is the first socio-ecological analysis of factors influencing young Aboriginal people's willingness to undertake testing for STIs within clinics in Australia. Strategies to improve uptake of STI testing must tackle the overlapping social and health service factors that discourage young people from seeking sexual health support. Much can be learned from young people's lived sexual health experiences and family- and community-based health promotion practices.

Remarkable progress has been achieved in understanding the mechanisms controlling sex determination, yet the cause for many Disorders of Sex Development (DSD) remains unknown. Of particular interest is a rare XX DSD subtype in which individuals are negative for SRY, the testis determining factor on the Y chromosome, yet develop testes or ovotestes, and both of these phenotypes occur in the same family. This is a naturally occurring disorder in humans (Homo sapiens) and dogs (C. familiaris). Phenotypes in the canine XX DSD model are strikingly similar to those of the human XX DSD subtype. The purposes of this study were to identify 1) a variant associated with XX DSD in the canine model and 2) gene expression alterations in canine embryonic gonads that could be informative to causation. Using a genome wide association study (GWAS) and whole genome sequencing (WGS), we identified a variant on C. familiaris autosome 9 (CFA9) that is associated with XX DSD in the canine model and in affected purebred dogs. This is the first marker identified for inherited canine XX DSD. It lies upstream of SOX9 within the canine ortholog for the human disorder, which resides on 17q24. Inheritance of this variant indicates that XX DSD is a complex trait in which breed genetic background affects penetrance. Furthermore, the homozygous variant genotype is associated with embryonic lethality in at least one breed. Our analysis of gene expression studies (RNA-seq and PRO-seq) in embryonic gonads at risk of XX DSD from the canine model identified significant RSPO1 downregulation in comparison to XX controls, without significant upregulation of SOX9 or other known testis pathway genes. Based on these data, a novel mechanism is proposed in which molecular lesions acting upstream of RSPO1 induce epigenomic gonadal mosaicism.

MOTIVATION: Shotgun sequence read data derived from xenograft material contains a mixture of reads arising from the host and reads arising from the graft. Classifying the read mixture to separate the two allows for more precise analysis to be performed. RESULTS: We present a technique, with an associated tool Xenome, which performs fast, accurate and specific classification of xenograft-derived sequence read data. We have evaluated it on RNA-Seq data from human, mouse and human-in-mouse xenograft datasets. AVAILABILITY: Xenome is available for non-commercial use from http://www.nicta.com.au/bioinformatics.

This study in children born extremely preterm (EP; <28 weeks' gestational age) or extremely low birth weight (ELBW; <1,000 g) investigated whether adaptive working memory training using Cogmed® is associated with structural and/or functional brain changes compared with a placebo program. Ninety-one EP/ELBW children were recruited at a mean (standard deviation) age of 7.8 (0.4) years. Children were randomly allocated to Cogmed or placebo (45-min sessions, 5 days a week over 5-7 weeks). A subset had usable magnetic resonance imaging (MRI) data pretraining and 2 weeks posttraining (structural, n = 48; diffusion, n = 43; task-based functional, n = 18). Statistical analyses examined whether cortical morphometry, white matter microstructure and blood oxygenation level-dependent (BOLD) signal during an n-back working memory task changed from pretraining to posttraining in the Cogmed and placebo groups separately. Interaction analyses between time point and group were then performed. There was a significant increase in neurite density in several white matter regions from pretraining to posttraining in both the Cogmed and placebo groups. BOLD signal in the posterior cingulate and precuneus cortices during the n-back task increased from pretraining to posttraining in the Cogmed but not placebo group. Evidence for group-by-time interactions for the MRI measures was weak, suggesting that brain changes generally did not differ between Cogmed and placebo groups. Overall, while some structural and functional MRI changes between the pretraining and posttraining period in EP/ELBW children were observed, there was little evidence of training-induced neuroplasticity, with changes generally identified in both groups. Trial registration Australian New Zealand Clinical Trials Registry, anzctr.org.au; ACTRN12612000124831.

BACKGROUND: Fluent word reading is a key characteristic of skilled reading, yet most children with reading disorders have impaired word-reading skills. Previous research has demonstrated that multi-component interventions targeting phonemic awareness and the alphabetic principle are effective for children with reading disorders. However, about 25% of children fail to respond to these interventions. While it has been difficult to isolate the active ingredient, the findings of some studies suggest that tasks targeting phonological recoding and orthographic processing are essential elements in improving decoding. AIMS: To develop and evaluate an intervention that specifically targets phonological recoding and orthographic processing (a decoding intervention) for children with persistent word-reading impairment. METHODS & PROCEDURES: A single-subject crossover design with multiple treatments was used to examine the efficacy of the decoding intervention (15 × 20-min sessions) compared with a language intervention that controlled for individual therapy time. Eight children (aged 7:6-8:11 years) with persistent word-reading impairment were randomly assigned to one of two intervention sequences. The effect of the decoding intervention was evaluated by (1) changes in decoding accuracy measured by performance on researcher-developed non-word lists; and (2) generalization to other standardized measures of reading. OUTCOMES & RESULTS: The results showed that all participants demonstrated significant gains in non-word reading on researcher-developed non-word lists and standardized measures of non-word-reading accuracy and efficiency. Trends for improvement on standardized measures of word-reading efficiency, text-reading accuracy and reading comprehension were observed. CONCLUSIONS & IMPLICATIONS: This decoding intervention significantly improved non-word decoding skills in all participants who had not responded to previous reading interventions. As such, it may be an efficient adjunct to the first stage of reading interventions for this population. The relative lack of generalization to other word-reading skills may have been due to the nature of the outcome measures, the short intervention time and/or additional delays in participant orthographic processing skills.

BACKGROUND: Bacterial vaginosis (BV) is the most common vaginal infection affecting women of childbearing age. While the aetiology and transmissibility of BV remain unclear, there is strong evidence to suggest an association between BV and sexual activity. This study explored women's views and experiences of the triggers for BV onset and factors associated with recurrence. METHODS: A descriptive, social constructionist approach was chosen as the framework for the study. Thirty five women of varying sexual orientation who had experienced recurrent BV in the past five years took part in semi-structured interviews. RESULTS: The majority of women predominantly reported sexual contact triggered the onset of BV and sexual and non-sexual factors precipitated recurrence. Recurrence was most commonly referred to in terms of a 'flare-up' of symptoms. The majority of women did not think BV was a sexually transmitted infection however many reported being informed this by their clinician. Single women who attributed BV onset to sex with casual partners were most likely to display self-blame tendencies and to consider changing their future sexual behaviour. Women who have sex with women (WSW) were more inclined to believe their partner was responsible for the transmission of or reinfection with BV and seek partner treatment or change their sexual practices. CONCLUSION: Findings from this study strongly suggest women believe that BV onset is associated with sexual activity, concurring with epidemiological data which increasingly suggest BV may be sexually transmitted. Exacerbating factors associated with recurrence were largely heterogeneous and may reflect the fact it is difficult to determine whether recurrence is due to persistent BV or a new infection in women. There was however evidence to suggest possible transmission and reinfection among WSW, reinforcing the need for new approaches to treatment and management strategies including male and female partner treatment trials.

BACKGROUND: Few data are available on how women manage recurring bacterial vaginosis (BV) and their experiences of the clinical care of this condition. This study aimed to explore women's recurrent BV management approaches and clinical care experiences, with a view to informing and improving the clinical management of BV. METHODS: A descriptive, social constructionist approach was chosen as the framework for the study. Thirty-five women of varying sexual orientation who had experienced recurrent BV in the past 5 years took part in semi-structured interviews. RESULTS: The majority of women reported frustration and dissatisfaction with current treatment regimens and low levels of satisfaction with the clinical management of BV. Overall, women disliked taking antibiotics regularly, commonly experienced adverse side effects from treatment and felt frustrated at having symptoms recur quite quickly after treatment. Issues in clinical care included inconsistency in advice, misdiagnosis and inappropriate diagnostic approaches and insensitive or dismissive attitudes. Women were more inclined to report positive clinical experiences with sexual health physicians than primary care providers. Women's frustrations led most to try their own self-help remedies and lifestyle modifications in an attempt to treat symptoms and prevent recurrences, including well-known risk practices such as douching. CONCLUSION: In the face of considerable uncertainty about the cause of BV, high rates of recurrence, unacceptable treatment options and often insensitive and inconsistent clinical management, women are trying their own self-help remedies and lifestyle modifications to prevent recurrences, often with little effect. Clinical management of BV could be improved through the use of standardised diagnostic approaches, increased sensitivity and understanding of the impact of BV, and the provision of evidence based advice about known BV related risk factors.