Acceptance and use of condoms among school-aged young people in Australia.

BACKGROUND: Despite availability of vaccines or medical prophylaxis for some sexually transmissible infections (STIs), promoting condom use remains an important public health strategy for the prevention of STIs. Recent research shows that regular condom use among young people in Australia has declined over the past decade, while the rate of common STIs has increased. METHOD: In this paper, we report findings from a large survey of school-aged young people in Australia (14-18years old) in which we looked at the association between condom use and positive feelings about sex, beliefs about social acceptability of condoms and confidence talking with partners about sex and condoms. RESULTS: Communication and relational factors supported more consistent condom use. Participants were more likely to regularly use condoms if they discussed condom use with a sexual partner, perceived condom use to be easy (a measure that included perceived ease of discussing condoms with a partner) and perceived condom use to offer social or relational benefits, including perceiving condom use as a demonstration of care for a partner. Young men were more likely to report positive feelings about sex and regular condom use than young women. Young women were less likely than young men or trans and non-binary young people to report regular condom use. CONCLUSIONS: The study shows the importance of supporting young people to build confidence expressing sexual needs and wants with partners. Public health approaches to STI prevention need to consider condom promotion in the context of young people's contemporary sexual, gendered and relationships cultures.

Homology-independent targeted insertion (HITI) enables guided CAR knock-in and efficient clinical scale CAR-T cell manufacturing.

BACKGROUND: Chimeric Antigen Receptor (CAR) T cells are now standard of care (SOC) for some patients with B cell and plasma cell malignancies and could disrupt the therapeutic landscape of solid tumors. However, access to CAR-T cells is not adequate to meet clinical needs, in part due to high cost and long lead times for manufacturing clinical grade virus. Non-viral site directed CAR integration can be accomplished using CRISPR/Cas9 and double-stranded DNA (dsDNA) or single-stranded DNA (ssDNA) via homology-directed repair (HDR), however yields with this approach have been limiting for clinical application (dsDNA) or access to large yields sufficient to meet the manufacturing demands outside early phase clinical trials is limited (ssDNA). METHODS: We applied homology-independent targeted insertion (HITI) or HDR using CRISPR/Cas9 and nanoplasmid DNA to insert an anti-GD2 CAR into the T cell receptor alpha constant (TRAC) locus and compared both targeted insertion strategies in our system. Next, we optimized post-HITI CRISPR EnrichMENT (CEMENT) to seamlessly integrate it into a 14-day process and compared our knock-in with viral transduced anti-GD2 CAR-T cells. Finally, we explored the off-target genomic toxicity of our genomic engineering approach. RESULTS: Here, we show that site directed CAR integration utilizing nanoplasmid DNA delivered via HITI provides high cell yields and highly functional cells. CEMENT enriched CAR T cells to approximately 80% purity, resulting in therapeutically relevant dose ranges of 5.5 × 108-3.6 × 109 CAR + T cells. CRISPR knock-in CAR-T cells were functionally comparable with viral transduced anti-GD2 CAR-T cells and did not show any evidence of off-target genomic toxicity. CONCLUSIONS: Our work provides a novel platform to perform guided CAR insertion into primary human T-cells using nanoplasmid DNA and holds the potential to increase access to CAR-T cell therapies.

Sexting and sexual behaviour in Australian adolescents.

BACKGROUND: Previous studies have tried to determine the relationship between sexting and risky behaviour to discover whether sexting fits into a deviance or normalcy discourse. This study investigated the relationship between sexting and sexual risk behaviours, contraception use and gender. METHODS: The design was a cross-sectional analysis of data from the sixth National Survey of Secondary Student and Adolescent Sexual Health, collected in 2018. There were 8263 Australian adolescents (aged 14-18years). Participants were fairly evenly split by gender, and 73% identified as heterosexual. Participants were asked a series of questions about their engagement in sexting, sexual behaviour and sexual health behaviours. RESULTS: A total of 52% of participants had sent a sext in the previous 2months, with most being text-based sexts. Sexters were 3.29times more likely to have engaged in anal or vaginal intercourse, and 2.88times more likely to have gotten pregnant than non-sexters. Sexters (M =2.76) had significantly more partners than non-sexters (M =2.35), t (3763)=-10.99, P X 2 (1)=0.38, P =0.535, or contraceptive use based on sexting status. CONCLUSIONS: Sexters are more likely to have engaged in sexual intercourse and have more partners than non-sexters. Sexting is not strongly associated with other risky behaviours. Evidence for differences between sexters and non-sexters in protecting against STIs and pregnancy was not found, as there were no significant differences in contraceptive use.

Profiling cognitive workload in an unmanned vehicle control task with cognitive models and physiological metrics.

In the present study, we use Cognitive Metrics Profiling (CMP) to capture variance in cognitive load within a complex unmanned vehicle control task. We aim to demonstrate convergent validity with existing workload measurement methods, and to decompose workload into constituent cognitive resources to aid in diagnosing causes of workload. A cognitive model of the task was developed and examined to determine the extent to which it could predict behavioral performance, subjective workload, and validated physiological workload metrics. We also examined model activity to draw insights regarding loaded cognitive capacities. We found that composite workload from the model predicted physiological metrics, performance, and subjective workload. Moreover, the model indicates that differences in workload were driven largely by procedural, declarative, and temporal memory demands. We have found preliminary evidence of correspondence between workload predictions of a CMP model and physiological measures of workload. This suggests our approach captures interesting aspects of workload in a complex task environment and may provide a theoretical link between behavioral, physiological, and subjective metrics. This approach may provide a means to design effective workload mitigation interventions and improve decision-making about personnel tasking and automation.

An evolutionarily ancient mechanism for regulation of hemoglobin expression in vertebrate red cells.

The oxygen transport function of hemoglobin (HB) is thought to have arisen ∼500 million years ago, roughly coinciding with the divergence between jawless (Agnatha) and jawed (Gnathostomata) vertebrates. Intriguingly, extant HBs of jawless and jawed vertebrates were shown to have evolved twice, and independently, from different ancestral globin proteins. This raises the question of whether erythroid-specific expression of HB also evolved twice independently. In all jawed vertebrates studied to date, one of the HB gene clusters is linked to the widely expressed NPRL3 gene. Here we show that the nprl3-linked hb locus of a jawless vertebrate, the river lamprey (Lampetra fluviatilis), shares a range of structural and functional properties with the equivalent jawed vertebrate HB locus. Functional analysis demonstrates that an erythroid-specific enhancer is located in intron 7 of lamprey nprl3, which corresponds to the NPRL3 intron 7 MCS-R1 enhancer of jawed vertebrates. Collectively, our findings signify the presence of an nprl3-linked multiglobin gene locus, which contains a remote enhancer that drives globin expression in erythroid cells, before the divergence of jawless and jawed vertebrates. Different globin genes from this ancestral cluster evolved in the current NPRL3-linked HB genes in jawless and jawed vertebrates. This provides an explanation of the enigma of how, in different species, globin genes linked to the same adjacent gene could undergo convergent evolution.

Social impacts of living with chronic hepatitis B in South Sudanese community in Australia.

Introduction: Chronic hepatitis B presents significant issues to public health and clinical practices. The infection requires lifelong clinical management and is a leading risk factor for liver cancer and liver cirrhosis. Limited studies currently exist on the social impacts of living with chronic hepatitis B, especially for people from Sub-Saharan Africa. The current study explored the experiences of South Sudanese people living with chronic hepatitis B in Australia.Methods: A qualitative inquiry using face-to-face interviews with fifteen South Sudanese people with chronic hepatitis B in Australia explored the social impacts of living with chronic hepatitis B. The study purposively sampled participants who self-identified as South Sudanese with hepatitis B and over 18 years of age. Interviews were coded and analysed using thematic analysis.Results: The study identified three themes relating to the experiences of living with chronic hepatitis B, and were grouped into psychological, interpersonal and healthcare system levels. Psychological level experiences related to the uncertainty of living with chronic hepatitis B and liver cancer risk, where participants expressed persistent fear of disease progression and anxiety around death related to the disease. Interpersonal level experiences involved the disclosure of hepatitis B and its social impacts including stigma, social distancing and isolation. Healthcare system level experiences included receiving mixed messages about hepatitis B, challenges with regular testing and difficulty receiving hepatitis B treatment.Conclusion: The findings provide valuable insights into the social impacts of hepatitis B. It underlines the importance of integrated public health interventions at the community level to improve knowledge and awareness of hepatitis B which address stigma in the South Sudanese community in Australia.

Descriptive norms about condom use predict odds of using a condom during last sexual experience in a large, national survey of adolescents from Australia.

BACKGROUND: Reducing sexually transmitted infections among adolescents is an important public health goal in Australia and worldwide. This study estimated the association between condom use during last heterosexual sexual experience with two descriptive norms among a large, national sample of secondary school students from Australia. METHODS: A large, national online survey of 14- to 18-year-olds in Australia was conducted in 2018; a sub-analysis of sexually active participants (n =2989) used multivariable logistic regression to estimate the relationships between condom use during last sexual experience and condom use norms. The analysis controlled for the effects of age, sex, sexual orientation, religious affiliation, remoteness and knowledge of sexually transmitted diseases. RESULTS: Overall, 1673 (56.0% [95% confidence interval: 54.2%, 57.8%]) sexually active respondents reported using condoms during their last sexual experience. Perceiving that all same-age peers used condoms conferred higher odds of using condoms during their last heterosexual sexual experience (adjusted odds ratio: 3.06 [95% CI: 1.6, 6.0]). Perceptions about whether the suggestion to initiate condom use came from boys, girls, or both boys and girls was not associated with condom use. Differences in condom use related to socio-demographic characteristics are reported. CONCLUSIONS: As part of a holistic approach to sexuality education, health educators and service providers may emphasise that young people frequently choose to use condoms.

Recapitulation of erythropoiesis in congenital dyserythropoietic anaemia type I (CDA-I) identifies defects in differentiation and nucleolar abnormalities.

The investigation of inherited disorders of erythropoiesis has elucidated many of the principles underlying the production of normal red blood cells and how this is perturbed in human disease. Congenital Dyserythropoietic Anaemia type 1 (CDA-I) is a rare form of anaemia caused by mutations in two genes of unknown function: CDAN1 and CDIN1 (previously called C15orf41), whilst in some cases, the underlying genetic abnormality is completely unknown. Consequently, the pathways affected in CDA-I remain to be discovered. To enable detailed analysis of this rare disorder we have validated a culture system which recapitulates all of the cardinal haematological features of CDA-I, including the formation of the pathognomonic 'spongy' heterochromatin seen by electron microscopy. Using a variety of cell and molecular biological approaches we discovered that erythroid cells in this condition show a delay during terminal erythroid differentiation, associated with increased proliferation and widespread changes in chromatin accessibility. We also show that the proteins encoded by CDAN1 and CDIN1 are enriched in nucleoli which are structurally and functionally abnormal in CDA-I. Together these findings provide important pointers to the pathways affected in CDA-I which for the first time can now be pursued in the tractable culture system utilised here.

Key Informants Discuss Cancer Care Research for Trans and Gender Diverse People.

The aim was to explore issues in relation to accessing cancer care for the Australian trans and gender diverse community through key informant interviews to inform a larger study on the topic. Semi-structured interviews were conducted with key informants who either had clinical and/or research experience with trans and gender diverse populations or were members of the community who act as advocates (total n = 14). Participants had diverse genders, including three transwomen, one transman, three non-binary people, six cis woman and one cis man. Thematic analysis was used to analyse the transcripts. Four themes were identified in the data: 'More Important Issues' than Cancer Concern, Experiences of Cancer Care, Barriers to Cancer Care and (Potential) Facilitating Factors to Access Cancer Care. The findings show the inconsistencies in awareness of cancer in the trans and gender diverse population, both within the community itself and in healthcare. There are issues concerning underutilization of screening services, healthcare workers lacking knowledge and an invisibility within organizations and systems. Education is needed in cancer care, as are partnerships with community organizations, inclusive policies, improved data collection on gender, targeted health promotion and research.

Prevalence Rates of Sexual Behaviors, Condom Use, and Contraception Among Australian Heterosexual Adolescents.

BACKGROUND: The development of effective health promotion practices and education programs to reduce rates of sexually transmitted infections and unintended pregnancy requires accurate, up-to-date information about young people's sexual behaviors. AIMS: To provide prevalence rates on sexual behaviors and condom and contraceptive use for Australian year 10-12 heterosexual students in a nationally representative sample. METHODS: A nationally representative sample of 2,301 male and 2,055 female year 10 through 12 heterosexual students were recruited to an online survey about their lifetime sexual behaviors and condom and contraceptive use. Means and 95% confidence intervals of weighted data, based on the national census, were reported. OUTCOMES: The main outcomes of this study were prevalence of sexual behaviors by gender (excluding trans and gender diverse) and prevalence of contraception and condom use among sexually active students by gender. RESULTS: The most common sexual behavior was masturbation (96.3% of male students, 78.9% of female students), and the least common behavior was anal or vaginal sex (43.7% of male students, 48.5% of female students). Of the sexually active students, condoms were used by 78.1% of male students and 77.5% of female students at first sexual experience and by 65.1% of male students and 56.8% of female students at their most recent sexual experience, whereas 91.6% of male students and 92.3% of female students used some form of contraception at most recent sexual experience. CLINICAL TRANSLATION: Results provide up-to-date information on the practices clinicians who are likely to encounter with heterosexual cisgender adolescent populations in Australia. STRENGTHS & LIMITAITONS: The study represents the largest representative cohort of adolescents in Australia to date. However, comparisons with previous representative studies were limited owing to differing samples by age and culture. CONCLUSIONS: Compared with earlier Australian studies, young heterosexual cisgender people today engage in slightly less oral and penetrative sexual behaviors, with the exception of more women receiving oral sex, and are generally consistent in condom and contraceptive use. Fisher CM, Kauer S, Mikolajczak G, et al. Prevalence Rates of Sexual Behaviors, Condom Use, and Contraception Among Australian Heterosexual Adolescents. J Sex Med 2020;17:2313-2321.

'It's kinda bad, honestly': Australian students' experiences of relationships and sexuality education.

Relationships and sexuality education for young people in Australia and elsewhere is a controversial topic. Numerous studies in Australia have focused on curriculum, policy, teachers, schools, sexting and other behaviours, and knowledge regarding sexually transmitted infection (STI)/human immunodeficiency virus (HIV) and pregnancy prevention. Few large-scale national studies have engaged with young people about what they want out of their sex education, and what they suggest would be most valuable for future programs in Australia. Data for the study included qualitative comments about experiences of sex education (n = 2316) provided in a national survey of adolescent sexual health. An initial thematic inductive analysis identified comments falling into two dominant themes: positive and negative experiences of their sex education. Results indicate that young people in Australia are articulate and understanding of the gaps in their sex education. A majority of comments highlighted negative experiences. These comments primarily discussed issues of delivery (timing, environment, person) and content quality (comprehensiveness). A minority highlighted positive commentary also around delivery (environment, person) and content quality (comprehensiveness). The findings of this study illuminate contemporary adolescent concerns regarding their experiences of education. Understanding these experiences can inform future curriculum development, teacher training and the design and implementation of policy.

The p.H63D allele of the HFE gene protects against low iron stores in Sri Lanka.

In hereditary hemochromatosis, iron overload is associated with homozygosity for the p.C282Y mutation. A second mutation, p.H63D, occurs at significant frequencies in Europe, North Africa, the Middle East and Asia. Early studies in Sri Lanka indicated that the variant had arisen independently, suggesting that it had been the subject of selective pressure. However, its role in iron absorption is unclear. In a survey of 7526 Sri Lankan secondary school students, we determined hemoglobin genotype and measured red cell indices, serum ferritin, transferrin receptor, iron zinc protoporphyrin and hepcidin. These variables were compared according to the presence or absence of the p.H63D variant in a subset of 1313 students for whom DNA samples were available. Students were classified as having low red cell indices if they had an MCV <80 fl and/or MCH <27 pg. Hetero and/or homozygosity for the p.H63D variant was more common in students with normal than low red cell indices (16.4% and 11.9% respectively; p = 0.019). Iron biomarkers and red cell indices were greater in children with the p.H63D variant than in normal and this was statistically significant for MCV (p = 0.046). Our findings suggest that selective pressure by mild iron deficiency contributes to the high frequencies of the p.H63D variant.

Small Molecule Antagonist of Cell Surface Glycosaminoglycans Restricts Mouse Embryonic Stem Cells in a Pluripotent State.

Recently, the field of stem cell-based regeneration has turned its attention toward chemical approaches for controlling the pluripotency and differentiation of embryonic stem cells (ESCs) using drug-like small molecule modulators. Growth factor receptors or their associated downstream kinases that regulate intracellular signaling pathways during differentiation are typically the targets for these molecules. The glycocalyx, which plays an essential role in actuating responses to growth factors at the cellular boundary, offers an underexplored opportunity for intervention using small molecules to influence differentiation. Here, we show that surfen, an antagonist of cell-surface glycosaminoglycans required for growth factor association with cognate receptors, acts as a potent and general inhibitor of differentiation and promoter of pluripotency in mouse ESCs. This finding shows that drugging the stem cell Glycome with small molecules to silence differentiation cues can provide a powerful new alternative to existing techniques for controlling stem cell fate. Stem Cells 2018;36:45-54.

Malignant and High-Risk Lesions in the Contralateral Breast Symmetry Mastopexy and Reduction Specimens When Performing Large-Volume Displacement Oncoplastic Surgery.

BACKGROUND: Large-volume displacement oncoplastic surgery using mastopexy/reduction mammaplasty designs is becoming increasingly popular in breast cancer surgery. A contralateral symmetry operation using similar mastopexy or breast reduction designs is also commonly performed by the plastic surgeon. Our goal was to analyze contralateral symmetry specimens to review the prevalence of high-risk or malignant lesions. METHODS: We conducted a retrospective study of the first consecutive 100 large-volume displacement oncoplastic surgeries at our institution between August 2015 and June 2018. Eighty-five patients had an immediate symmetry operation performed on the contralateral breast. Information on malignant lesions and high-risk lesions was obtained from the patient's pathology report. RESULTS: Seven different surgical techniques were used for both the cancerous and contralateral breasts. The WISE pattern skin incision pattern was most frequently used, along with the superomedial pedicle design. Fourteen cases (16.5%) had malignant and/or high-risk lesions incidentally detected. Specifically, there was a breast cancer prevalence of 4.8% in the contralateral symmetry breast specimen. CONCLUSION: Plastic surgeons should be aware that there is a substantial minority of contralateral specimens that have high-risk or malignant lesions, which underscores the importance of specimen orientation and communication with the associated pathologist.

Haemoglobin variants, iron status and anaemia in Sri Lankan adolescents with low red cell indices: A cross sectional survey.

Iron deficiency complicates the use of red cell indices to screen for carriers of haemoglobin variants in many populations. In a cross sectional survey of 7526 secondary school students from 25 districts of Sri Lanka, 1963 (26.0%) students had low red cell indices. Iron deficiency, identified by low serum ferritin, was the major identifiable cause occurring in 550/1806 (30.5%) students. Low red cell indices occurred in iron-replete students with alpha-thalassaemia including those with single alpha-globin gene deletions. Anaemia and low red cell indices were also common in beta-thalassaemia trait. An unexpected finding was that low red cell indices occurred in 713 iron-replete students with a normal haemoglobin genotype. It is common practice to prescribe iron supplements to individuals with low red cell indices. Since low red cell indices were a feature of all forms of α thalassaemia and also of iron deficiency, in areas where both conditions are common, such as Sri Lanka, it is imperative to differentiate between the two, to allow targeted administration of iron supplements and avoid the possible deleterious effects of increased iron availability in iron replete individuals with low red cell indices due to other causes such as α thalassaemia.

Top-down influence on the visual cortex of the blind during sensory substitution.

Visual sensory substitution devices provide a non-surgical and flexible approach to vision rehabilitation in the blind. These devices convert images taken by a camera into cross-modal sensory signals that are presented as a surrogate for direct visual input. While previous work has demonstrated that the visual cortex of blind subjects is recruited during sensory substitution, the cognitive basis of this activation remains incompletely understood. To test the hypothesis that top-down input provides a significant contribution to this activation, we performed functional MRI scanning in 11 blind (7 acquired and 4 congenital) and 11 sighted subjects under two conditions: passive listening of image-encoded soundscapes before sensory substitution training and active interpretation of the same auditory sensory substitution signals after a 10-minute training session. We found that the modulation of visual cortex activity due to active interpretation was significantly stronger in the blind over sighted subjects. In addition, congenitally blind subjects showed stronger task-induced modulation in the visual cortex than acquired blind subjects. In a parallel experiment, we scanned 18 blind (11 acquired and 7 congenital) and 18 sighted subjects at rest to investigate alterations in functional connectivity due to visual deprivation. The results demonstrated that visual cortex connectivity of the blind shifted away from sensory networks and toward known areas of top-down input. Taken together, our data support the model of the brain, including the visual system, as a highly flexible task-based and not sensory-based machine.

Geospatial revolution and remote sensing LiDAR in Mesoamerican archaeology.

The application of light detection and ranging (LiDAR), a laser-based remote-sensing technology that is capable of penetrating overlying vegetation and forest canopies, is generating a fundamental shift in Mesoamerican archaeology and has the potential to transform research in forested areas world-wide. Much as radiocarbon dating that half a century ago moved archaeology forward by grounding archaeological remains in time, LiDAR is proving to be a catalyst for an improved spatial understanding of the past. With LiDAR, ancient societies can be contextualized within a fully defined landscape. Interpretations about the scale and organization of densely forested sites no longer are constrained by sample size, as they were when mapping required laborious on-ground survey. The ability to articulate ancient landscapes fully permits a better understanding of the complexity of ancient Mesoamerican urbanism and also aids in modern conservation efforts. The importance of this geospatial innovation is demonstrated with newly acquired LiDAR data from the archaeological sites of Caracol, Cayo, Belize and Angamuco, Michoacán, Mexico. These data illustrate the potential of technology to act as a catalytic enabler of rapid transformational change in archaeological research and interpretation and also underscore the value of on-the-ground archaeological investigation in validating and contextualizing results.