Testosterone and the heart: friend or foe?

Cardiovascular disease (CVD) is the leading cause of death in women aged 65 years and older. Sex hormones have been implicated as having a critical role in the evolution of CVD, with the focus mainly on estrogens in women. Available data also indicate that low testosterone blood levels may be detrimental to cardiovascular function in women. At blood concentrations considered normal for premenopausal women, testosterone has favorable effects on blood vessel function (relaxation and contraction), much of which is determined by the endothelial cells that line the inside of blood vessels. Testosterone enhances endothelium-dependent and independent brachial artery vasodilation and has an acute systolic blood pressure-lowering effect in postmenopausal women. Advantageous effects of testosterone in animal models have been seen for myocardial function and cardiac electrical signaling. Human data are mainly limited to observational and mechanistic studies, which mostly demonstrate beneficial effects of testosterone on cardiovascular health. Few studies of testosterone use in women, with cardiovascular endpoints as primary outcomes, have been published.

Higher testosterone is associated with higher HDL-cholesterol and lower triglyceride concentrations in older women: an observational study.

OBJECTIVE: This study aimed to determine whether concentrations of testosterone and its main precursor after menopause, dehydroepiandrosterone (DHEA), are associated with lipoproteins and other lipids in community-dwelling older women. METHODS: The Sex Hormones in Older Women (SHOW) study was an observational study of 6358 Australian women, aged at least 70 years, with no prior major adverse cardiovascular event who had sex hormones measured by liquid chromatography-tandem mass spectrometry. Associations between hormones and lipids were examined using multilinear regression adjusted for potential confounders. RESULTS: The cross-sectional analyses included 3231 participants, median age 74.0 (interquartile range 71.7-77.9) years. Compared with concentrations in the lowest quartile (Q1), testosterone concentrations in the highest quartiles (Q3 and Q4) were positively associated with high-density lipoprotein cholesterol (HDL-C) (p = 0.002 and p < 0.001, respectively) while Q4 testosterone concentrations were positively associated with total cholesterol (p = 0.038). Q2, Q3 and Q4 testosterone concentrations were significantly inversely associated with triglycerides (TG) (p = 0.024, p = 0.003 and p < 0.001, respectively). For DHEA, Q4 concentrations was positively associated with non-HDL-C (p = 0.024). CONCLUSIONS: In older women, higher endogenous testosterone concentrations are significantly associated with higher HDL-C and lower TG, indicating a less atherogenic profile. These findings suggest a neutral, or potentially protective, cardiovascular disease effect of testosterone in older women.

Testosterone for women: certainties and uncertainties.

The clinical effects of testosterone in women have expanded from the field of androgen excess to consideration of testosterone action and the consequences of depletion and replacement. This article is not a comprehensive review of the vast and increasing literature in this field. Rather, it summarizes some of what is known of testosterone in women that the author elected to highlight in a plenary lecture and is hopefully informative, but not to be considered conclusive.

Menopause symptoms, sexual dysfunctions and pelvic floor disorders in refugee and asylum seeker women: a scoping review.

Refugee and asylum seeker women face a variety of health challenges. However, little is known globally about health problems in these women at midlife and beyond, including menopausal symptoms, sexual dysfunctions and pelvic floor disorders. This scoping review aimed to understand these neglected health issues with respect to prevalence and risk factors. Eight databases were searched in August 2022 without the limit of publication year. Data were analyzed narratively. A total of 10 reports from seven studies were included with 945 women living in Australia, Canada, the USA and Pakistan. Three reports were addressing menopause, seven addressed sexual dysfunctions and one addressed pelvic floor disorders. There were no data regarding menopause symptoms; however, perceptions of menopause varied widely across studies. Few studies reported a high prevalence of sexual dysfunctions and pelvic organ prolapses, but none of them used a validated questionnaire. Taboos and cultural factors, lack of knowledge and education, lack of family support, language insufficiency and financial problems were common barriers to not seeking care for these health issues. This review demonstrates lack of evidence of these neglected health issues in refugee and asylum seeker women at midlife, and further studies with validated questionnaires and larger samples are warranted.

Association between testosterone and cognitive performance in postmenopausal women: a systematic review of observational studies.

This review was conducted to explore the association between endogenous testosterone blood concentrations and cognitive performance among community dwelling postmenopausal women. We searched Ovid MEDLINE, EMBASE, PsycINFO and Web of Science databases for observational studies with at least 100 postmenopausal participants. The results were categorized by study design, reporting of total or free testosterone and risk of bias assessments, narratively. Ten of the 26 articles retrieved for full-text review met the inclusion criteria, six provided cross-sectional data, seven provided longitudinal data and one provided case-control data. Cognitive performance tests differed between studies. Eight studies measured testosterone by immunoassay, one by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and one did not specify their methodology. Eleven different cognitive domains were tested by 37 different instruments. Irrespective of the study design, the findings were inconsistent and inconclusive. Both positive and inverse associations were reported for each of global cognition and immediate and delayed verbal recall. The majority of studies reported no association between total or free testosterone and cognitive performance. Although this review did not demonstrate an association between testosterone and cognitive performance in postmenopausal women, the findings should be considered inconclusive due to the imprecision of testosterone measurement and the methodological heterogeneity of the included studies.

Sex hormones, SHBG and cognitive performance among older Australian women: an observational study.

OBJECTIVE: This study aims to explore the associations between sex hormones and cognitive performance in older women. METHODS: Associations between sex hormones, sex hormone binding globulin (SHBG) and cognitive performance were examined in women aged at least 70 years, without dementia and not using medications that influence sex hormones. Linear and generalized linear regression models included age, body mass index, education, smoking, alcohol, living circumstances, diabetes, hypertension, depression and impaired renal function. RESULTS: The included 5511 women had a median (interquartile range) age of 73.9 (71.6-77.6) years. No associations were found for estrone, estradiol, testosterone or dehydroepiandrosterone and cognitive performance. SHBG concentrations above quartile 1 (Q1) were significantly inversely associated with processing speed (Q2, ß = -0.94, 95% confidence interval [CI] - 1.64 to -0.24, p = 0.009; Q3, ß = -0.82, 95% CI -1.53 to -0.10, p = 0.025; and Q4, ß = -0.95, 95% CI -1.70 to -0.20, p = 0.013). CONCLUSIONS: Sex hormones were not associated with cognitive performance. The finding that low SHBG is associated with better processing speed warrants further investigation. The null findings for the sex hormones establish a firm baseline to confidently explore the association between sex hormones and longitudinal cognitive performance in this population. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Register (ISRCTN83772183) and ClinicalTrials.gov (NCT01038583).

The 2023 Practitioner's Toolkit for Managing Menopause.

OBJECTIVE: The Practitioner's Toolkit for Managing the Menopause, developed in 2014, provided an accessible desk-top tool for health-care practitioners caring for women at midlife. To ensure the Toolkit algorithms and supporting information reflect current best practice, the Toolkit has been revised in accordance with the published literature. METHODS: A systematic search for guidelines, position and consensus statements pertaining to the menopause and published after 2014 was undertaken, and key recommendations extracted from the Clinical Practice Guidelines determined to be the most robust by formal evaluation. The peer-reviewed literature was further searched for identified information gaps. RESULTS: The revised Toolkit provides algorithms that guide the clinical assessment and care of women relevant to menopause. Included are the reasons why women present, information that should be ascertained, issues that may influence shared decision-making and algorithms that assist with determination of menopausal status, menopause hormone therapy (MHT) and non-hormonal treatment options for symptom relief. As clear guidelines regarding when MHT might be indicated to prevent bone loss and subsequent osteoporosis in asymptomatic women were found to be lacking, the Toolkit has been expanded to support shared decision-making regarding bone health. CONCLUSIONS: The 2023 Toolkit and supporting document provide accessible desk-top information to support health-care providers caring for women at midlife.The Toolkit has been endorsed by the International Menopause Society, Australasian Menopause Society, British Menopause Society, Endocrine Society of Australia and Jean hailes for Women's Health.

Estrone, sex hormone binding globulin and lipid profiles in older women: an observational study.

OBJECTIVE: We investigated whether estrone and sex hormone binding globulin (SHBG) concentrations are associated with lipid concentrations in older postmenopausal women. METHODS: This was a cross-sectional study of 6358 Australian women, aged 70-95 years, recruited between 2010 and 2014. Associations between estrone and SHBG and lipid concentrations were examined in participants not using medications that influence estrogen concentrations or lipid-lowering therapy. Linear regression models included age, body mass index, smoking, alcohol consumption, renal function and diabetes, with the lowest quartile (Q1) as the reference for estrone and SHBG. RESULTS: The study included 3231 participants with median age of 74.0 (interquartile range 71.7-77.9) years. Estrone concentration Q3 and Q4 were positively associated with high-density lipoprotein cholesterol (HDL-C) (p = 0.017 and p = 0.046, respectively). Inverse associations were seen for estrone Q4 with total cholesterol (p = 0.018), Q2 and Q4 with non-HDL-C (p = 0.045 and p = 0.002, respectively) and Q3 and Q4 with triglycerides (p = 0.030 and p = 0.001, respectively). For SHBG, Q2, Q3 and Q4 were positively associated with HDL-C (all p < 0.001), and inversely with non-HDL-C (all p = 0.001) and triglycerides (all p < 0.001). CONCLUSIONS: Estrone and SHBG are associated with lipid concentrations in older women. SHBG, but not estrone, may provide additional clinical predictive utility for the assessment of cardiometabolic disease risk in older women.

Pregnancy status predicted using milk mid-infrared spectra from dairy cattle.

Accurate and timely pregnancy diagnosis is an important component of effective herd management in dairy cattle. Predicting pregnancy from Fourier-transform mid-infrared (FT-MIR) spectroscopy data is of particular interest because the data are often already available from routine milk testing. The purpose of this study was to evaluate how well pregnancy status could be predicted in a large data set of 1,161,436 FT-MIR milk spectra records from 863,982 mixed-breed pasture-based New Zealand dairy cattle managed within seasonal calving systems. Three strategies were assessed for defining the nonpregnant cows when partitioning the records according to pregnancy status in the training population. Two of these used records for cows with a subsequent calving only, whereas the third also included records for cows without a subsequent calving. For each partitioning strategy, partial least squares discriminant analysis models were developed, whereby spectra from all the cows in 80% of herds were used to train the models, and predictions on cows in the remaining herds were used for validation. A separate data set was also used as a secondary validation, whereby pregnancy diagnosis had been assigned according to the presence of pregnancy-associated glycoproteins (PAG) in the milk samples. We examined different ways of accounting for stage of lactation in the prediction models, either by including it as an effect in the prediction model, or by pre-adjusting spectra before fitting the model. For a subset of strategies, we also assessed prediction accuracies from deep learning approaches, utilizing either the raw spectra or images of spectra. Across all strategies, prediction accuracies were highest for models using the unadjusted spectra as model predictors. Strategies for cows with a subsequent calving performed well in herd-independent validation with sensitivities above 0.79, specificities above 0.91 and area under the receiver operating characteristic curve (AUC) values over 0.91. However, for these strategies, the specificity to predict nonpregnant cows in the external PAG data set was poor (0.002-0.04). The best performing models were those that included records for cows without a subsequent calving, and used unadjusted spectra and days in milk as predictors, with consistent results observed across the training, herd-independent validation and PAG data sets. For the partial least squares discriminant analysis model, sensitivity was 0.71, specificity was 0.54 and AUC values were 0.68 in the PAG data set; and for an image-based deep learning model, the sensitivity was 0.74, specificity was 0.52 and the AUC value was 0.69. Our results demonstrate that in pasture-based seasonal calving herds, confounding between pregnancy status and spectral changes associated with stage of lactation can inflate prediction accuracies. When the effect of this confounding was reduced, prediction accuracies were not sufficiently high enough to use as a sole indicator of pregnancy status.

An observational study on the relationship between zinc concentrations in bulk tank milk and in serum and farmer-reported zinc supplementation of dairy cattle for facial eczema prophylaxis.

AIMS: To describe the concentration of Zn in bulk tank milk (BTM) in a sample of New Zealand dairy farms, investigate the association between the method of Zn administration for facial eczema prophylaxis and Zn concentrations in BTM and investigate the relationship between the concentration of Zn in serum and that in BTM. METHODS: Multiple BTM samples (n = 3,330) collected during milk pick-up by the milk tanker driver were stored and tested for 121 farms, in Northland (n = 50), Waikato (n = 51) and Southland (n = 20) from February to May 2017. Enrolled farms provided retrospective information on the type of Zn supplementation (if any) used for the prevention of facial eczema and the timeframe over which supplementation occurred. In addition, the concentration of Zn in serum was measured in blood samples collected from ≥15 cattle per farm for 22 farms from Northland (n = 11) and Waikato (n = 11), and compared against the concentrations of Zn in BTM on the day of blood sampling. A linear mixed model was used to model log Zn concentrations in BTM using method of Zn supplementation, region, milk fat and protein percentage, volume of milk, and frequency of milk pick-up as risk factors. A mixed logistic regression model was used to assess the relationship between Zn concentrations in BTM and the presence of cows with a concentration of Zn in serum of ≥20 µmol/L. RESULTS: The median Zn concentration in BTM was 67.9 (min 38.9, max 146.6) µmol/L. The median range of Zn concentrations for repeated samples of BTM within farm was 22.6 µmol/L. In comparison to farms that did not use any form of Zn supplementation, farms that supplemented Zn through a slow-release capsule, oral drench, in feed or a combination of in-feed and water were associated with increased concentrations of Zn in BTM (p < 0.001). There was no difference in Zn concentrations in BTM between farms that administered Zn through the water only and farms that did not administer Zn (p = 0.22). Every 15.3 µmol/L increase in Zn concentration in BTM was associated with 2.2 times (95% CI=1.7-2.9) the odds of a cow having Zn concentration in serum ≥20 µmol/L. CONCLUSION AND CLINICAL RELEVANCE: Zn concentration in BTM is highly variable between farms, days and Zn administration method. Zn concentration in BTM content has modest potential as a way to signal whether a herd has achieved the high Zn status considered to be protective against FE.

Quantification of zinc concentrations in serum, milk and faeces of dairy cattle as a measure of effective zinc supplementation for management of facial eczema.

AIMS: To investigate the relationship between Zn concentrations in serum and those in milk or faeces, and to assess the ability of the Zn concentrations in milk, serum and faeces to predict intake of ZnO in dairy cattle. METHOD: Seventy cows from one commercial farm in the Waikato region of New Zealand received one of seven dose rates (0, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5 g/100 kg bodyweight (BW)) of ZnO given by oral drench, every morning, for 7 consecutive days. Every afternoon, milk and blood samples were collected from all cows. Free-catch faecal samples were collected during the afternoon milking on 3 days throughout the trial.Linear mixed models were used to assess the relationship between the concentration of Zn in serum and that in milk, and in faeces, respectively, and the relationship between dose rate of ZnO and concentrations of Zn in serum, faeces and milk, respectively. Receiver operating characteristic curve analysis was used to determine the ability of the Zn concentration in serum, milk and faeces to predict that a cow had been treated with a dose of ZnO ≥2.5 g/100 kg, the industry-recommended dose rate needed to protect against facial eczema. RESULTS: A 1-µmol/L increase in Zn concentration in milk was associated with a 0.14 (95% CI = 0.11-0.17) µmol/L increase in Zn concentration in serum. Zn concentration in faeces was scaled by its SD; a 1 SD increase was associated with a 1.83 (95% CI = 0.54-3.12) µmol/L increase in zinc concentration in serum. Zn concentrations in serum and faeces increased with increasing dose rates of ZnO. No differences in Zn concentrations in milk were noted between animals dosed with 1.5-3.5 g ZnO/100 kg BW, inclusive. At the optimal threshold of Zn concentration in serum to predict protective ZnO intake (22 µmol/L), the sensitivity was 0.76 (95% CI = 0.69-0.82) and specificity 0.85 (95% CI = 0.80-0.89). For the concentration of Zn in faeces, the optimal threshold was 17.36 mmol/kg, with a corresponding sensitivity of 0.84 (95% CI = 0.84-0.85) and specificity of 0.85 (95% CI = 0.73-0.94). At the optimal threshold for the Zn concentration in milk (76.6 µmol/L), the sensitivity was lower than the other two sample types at 0.59 (95% CI = 0.52-0.67), but with a similar specificity of 0.84 (95% CI = 0.79-0.88). CONCLUSIONS AND CLINICAL RELEVANCE: The concentration of Zn in milk shows promise as an initial screening test to identify dairy farms that do not provide adequate zinc to provide protection against FE.

Androgens in premenopausal women and women with premature ovarian insufficiency.

Premature ovarian insufficiency (POI) results in both estrogen and testosterone insufficiency. Whether testosterone therapy may be of benefit for women with POI is uncertain. Presently, the only evidence-based indication for testosterone therapy for women is for the treatment of postmenopausal women with low sexual desire with associated personal distress. Consistent with this, available evidence does not support the prescription of testosterone to prevent cardiometabolic disease, bone loss, sarcopenia, or cognitive decline or to improve well-being and low mood in postmenopausal women. Data pertaining to the treatment of women with POI with testosterone are limited. This article reviews androgen physiology in premenopausal women and the impact of POI on circulating androgen concentrations, summarizes findings from observational studies and clinical trials of testosterone therapy in premenopausal women and women with POI, and concludes with recommendations regarding testosterone use in women with POI.

Testosterone use in postmenopausal women.

The physiological, clinical and therapeutic aspects of testosterone in women's health are still a matter of controversy and debate. Quality evidence data of clinical trials favors the use of transdermal testosterone in postmenopausal women with female sexual dysfunction causing distress. Doses of testosterone should approximate physiological testosterone levels found in premenopausal women, avoiding supraphysiological concentrations that expose women to adverse events. Short-term treatment periods have been shown to be effective and safe in postmenopausal women with hypoactive sexual desire disorder/dysfunction. However, long-term safety of testosterone use must be determined.

Health-care providers' views of menopause and its management: a qualitative study.

OBJECTIVE: This study aimed to explore Australian health-care providers' knowledge of menopause and its consequences, and their views about menopause-related health care. METHODS: This was a cross-sectional qualitative study of Australian general practitioners (GPs), gynecologists (GYs) and pharmacists (PHs). Recruitment was ultimately achieved through professional networks and cold calling. RESULTS: There were equal numbers of GPs, GYs and PHs, and equal numbers of males and females in each group. All participants demonstrated sound understanding of menopause and its consequences. A strong theme was recognition of high usage of complementary and alternative medicines (CAMs) by women for menopausal symptoms. Most participants highlighted lack of efficacy evidence for most CAMs, but the majority of GPs and PHs considered CAMs to 'have a role'. Most supported menopausal hormone therapy (MHT) when symptoms impaired quality of life. Limitations to comprehensive care included knowledge gaps and lack of time. CONCLUSIONS: Australian health-care providers appeared knowledgeable about menopause, but uncertain about its management. MHT prescription appeared limited to women with severe symptoms despite lifestyle modification and a trial of CAMs. The upskilling of clinicians providing care for women at midlife, with respect to the indications for and prescribing of MHT, urgently needs to be addressed.

Australian women's understanding of menopause and its consequences: a qualitative study.

BACKGROUND: This study was undertaken to determine women's knowledge of menopause and its consequences, and their menopause-related health-care experiences. METHODS: Participants were recruited to this cross-sectional qualitative study from a nationally, representative sample of Australian women. Recruitment was stratified by age to achieve groups of premenopausal (PRE), perimenopausal (PERI), early postmenopausal (E-POST), and late postmenopausal (L-POST) women. RESULTS: The 32 participants were aged 46-69 years: 10 PRE, three PERI, 11 E-POST and eight L-POST women. All understood that menopause meant the end of reproductive function and were aware of menopause-associated symptoms. Most PRE and E-POST women referred to lifestyle changes to optimize health, and self-help and complementary therapies to manage symptoms. E-POST and L-POST women were more likely to nominate seeing a doctor for overall health and symptom management. Menopausal hormone therapy (MHT) was viewed negatively, with shared perceptions of cancer risk and over-prescription. A strong theme was lack of knowledge of long-term menopause sequelae, with only four women nominating osteoporosis. CONCLUSIONS: Our in-depth qualitative study would suggest that, while Australian midlife women have a good understanding of the immediate effects of menopause, their lack of knowledge of the long-term consequences is concerning. Despite the effectiveness and safety of MHT, the overall attitude to MHT remains negative.

Genetic correlations of milk fatty acid contents predicted from milk mid-infrared spectra in New Zealand dairy cattle.

The objective of this study was to estimate genetic correlations among milk fatty acid (FA) concentrations in New Zealand dairy cattle. Concentrations of each of the most common FA, expressed as a percentage of the total FA, were determined by gas chromatography on a specific cohort of animals. Using this data set, prediction equations were derived using mid-infrared (MIR) spectroscopy data collected from the same samples. These prediction equations were applied to a large data set of MIR measurements in 34,141 milk samples from 3,445 Holstein-Friesian, 2,935 Jersey, and 3,609 crossbred Holstein-Friesian × Jersey cows, sampled an average of 3.42 times during the 2007-2008 season. Data were analyzed using univariate and bivariate repeatability animal models. Heritability of predicted FA concentration in milk fat ranged from 0.21 to 0.42, indicating that genetic selection could be used to change the FA composition of milk. The de novo synthesized FA (C6:0, C8:0, C10:0, C12:0, and C14:0) showed strong positive genetic correlations with each other, ranging from 0.24 to 0.99. Saturated FA were negatively correlated with unsaturated (-0.93) and polyunsaturated (-0.84) FA. The saturated FA were positively correlated with milk fat yield and fat percentage, whereas the unsaturated FA were negatively associated with fat yield and fat percentage. Our results indicate that bovine milk FA composition can be changed through genetic selection using MIR as a phenotypic proxy.

Strategies for noise reduction and standardization of milk mid-infrared spectra from dairy cattle.

The use of Fourier-transform mid-infrared (FTIR) spectroscopy is of interest to the dairy industry worldwide for predicting milk composition and other novel traits that are difficult or expensive to measure directly. Although there are many valuable applications for FTIR spectra, noise from differences in spectral responses between instruments is problematic because it reduces prediction accuracy if ignored. The purpose of this study was to develop strategies to reduce the impact of noise and to compare methods for standardizing FTIR spectra in order to reduce between-instrument variability in multiple-instrument networks. Noise levels in bands of the infrared spectrum caused by the water content of milk were characterized, and a method for identifying and removing outliers was developed. Two standardization methods were assessed and compared: piecewise direct standardization (PDS), which related spectra on a primary instrument to spectra on 5 other (secondary) instruments using identical milk-based reference samples (n = 918) analyzed across the 6 instruments; and retroactive percentile standardization (RPS), whereby percentiles of observed spectra from routine milk test samples (n = 2,044,094) were used to map and exploit primary- and secondary-instrument relationships. Different applications of each method were studied to determine the optimal way to implement each method across time. Industry-standard predictions of milk components from 2,044,094 spectra records were regressed against predictions from spectra before and after standardization using PDS or RPS. The PDS approach resulted in an overall decrease in root mean square error between industry-standard predictions and predictions from spectra from 0.190 to 0.071 g/100 mL for fat, from 0.129 to 0.055 g/100 mL for protein, and from 0.143 to 0.088 g/100 mL for lactose. Reductions in prediction error for RPS were similar but less consistent than those for PDS across time, but similar reductions were achieved when PDS coefficients were updated monthly and separate primary instruments were assigned for the North and South Islands of New Zealand. We demonstrated that the PDS approach is the most consistent method to reduce prediction errors across time. We also showed that the RPS approach is sensitive to shifts in milk composition but can be used to reduce prediction errors, provided that secondary-instrument spectra are standardized to a primary instrument with samples of broadly equivalent milk composition. Appropriate implementation of either of these approaches will improve the quality of predictions based on FTIR spectra for various downstream applications.

Short communication: Identification of the pseudoautosomal region in the Hereford bovine reference genome assembly ARS-UCD1.2.

In cattle, the X chromosome accounts for approximately 3 and 6% of the genome in bulls and cows, respectively. In spite of the large size of this chromosome, very few studies report analysis of the X chromosome in genome-wide association studies and genomic selection. This lack of genetic interrogation is likely due to the complexities of undertaking these studies given the hemizygous state of some, but not all, of the X chromosome in males. The first step in facilitating analysis of this gene-rich chromosome is to accurately identify coordinates for the pseudoautosomal boundary (PAB) to split the chromosome into a region that may be treated as autosomal sequence (pseudoautosomal region) and a region that requires more complex statistical models. With the recent release of ARS-UCD1.2, a more complete and accurate assembly of the cattle genome than was previously available, it is timely to fine map the PAB for the first time. Here we report the use of SNP chip genotypes, short-read sequences, and long-read sequences to fine map the PAB (X chromosome:133,300,518) and simultaneously determine the neighboring regions of reduced homology and true pseudoautosomal region. These results greatly facilitate the inclusion of the X chromosome in genome-wide association studies, genomic selection, and other genetic analysis undertaken on this reference genome.

"Kiss myAsthma": Using a participatory design approach to develop a self-management app with young people with asthma.

Objective: Young people with asthma often lack engagement in self-management. Smartphone apps offer an attractive, immediate method for obtaining asthma information and self-management support. In this research we developed an evidence-based asthma app tailored to young peoples needs, created using a participatory design approach to optimize user engagement. This paper describes the participatory design process. Methods: This multi-phased research included concept generation and ideation of app design by young people with asthma, and development of asthma information by the research team. Clinical review was sought regarding safety and accuracy of app content. Participants suggestions for improvement and any problems with the app were logged throughout. Our young co-designers were invited back to test a high fidelity prototype app using a "think aloud" process and completed a usability questionnaire. Results: Twenty asthma patients aged 15-24 years contributed to the initial app design. Three respiratory specialists and two pharmacists suggested minor corrections to clinical terminology in the app which were all incorporated. Nine co-designers acted as expert reviewers of the prototype app, of whom eight completed a usability questionnaire. Median usability scores (maximum score 6) indicated high satisfaction with app content, usefulness and ease of use [median item score 5.3 (range 4.7-6.0)]. All feedback was incorporated to create an updated prototype app. Conclusions: A clinically sound asthma app has been developed which is considered highly acceptable to the young co-designers. A six-week test of the engagement, acceptability, and usefulness of the app in young people not involved in the participatory design will follow.