Azithromycin or Doxycycline for Asymptomatic Rectal Chlamydia trachomatis.

BACKGROUND: Rectal chlamydia is a common bacterial sexually transmissible infection among men who have sex with men. Data from randomized, controlled trials are needed to guide treatment. METHODS: In this double-blind trial conducted at five sexual health clinics in Australia, we randomly assigned men who have sex with men and who had asymptomatic rectal chlamydia to receive doxycycline (100 mg twice daily for 7 days) or azithromycin (1-g single dose). Asymptomatic chlamydia was selected as the trial focus because more than 85% of men with rectal chlamydia infection are asymptomatic, and clinical guidelines recommend a longer treatment course for symptomatic infection. The primary outcome was a negative nucleic acid amplification test for rectal chlamydia (microbiologic cure) at 4 weeks. RESULTS: From August 2016 through August 2019, we enrolled 625 men (314 in the doxycycline group and 311 in the azithromycin group). Primary outcome data were available for 290 men (92.4%) in the doxycycline group and 297 (95.5%) in the azithromycin group. In the modified intention-to-treat population, a microbiologic cure occurred in 281 of 290 men (96.9%; 95% confidence interval [CI], 94.9 to 98.9) in the doxycycline group and in 227 of 297 (76.4%; 95% CI, 73.8 to 79.1) in the azithromycin group, for an adjusted risk difference of 19.9 percentage points (95% CI, 14.6 to 25.3; P<0.001). Adverse events that included nausea, diarrhea, and vomiting were reported in 98 men (33.8%) in the doxycycline group and in 134 (45.1%) in the azithromycin group (risk difference, -11.3 percentage points; 95% CI, -19.5 to -3.2). CONCLUSIONS: A 7-day course of doxycycline was superior to single-dose azithromycin in the treatment of rectal chlamydia infection among men who have sex with men. (Funded by the National Health and Medical Research Council; RTS Australian New Zealand Clinical Trials Registry number, ACTRN12614001125617.).

Sleep-disordered breathing in children and adults with intellectual disability: mind the gap!

BACKGROUND: In adults and children with intellectual disability (ID), sleep -disordered breathing (SDB) is thought to be common. However, large epidemiological studies are lacking, and there are few studies on optimal methods of investigation and even fewer randomised, controlled intervention trials of treatment. METHOD: Peer-reviewed publications from various databases were examined in line with search terms relevant to ID and SDB spanning the years 200-2024. RESULTS: Findings suggest that, due to comorbid conditions, children and adults with ID may experience both an increased risk of SDB, as well as lower frequency of diagnosis. SDB can compromise the emotional, physical and mental health of individuals with ID. Appropriate treatment when tolerated leads to an improvement in health and well-being and several studies emphasized the importance of consistent follow-up of people with ID - something that is not universally occurring during childhood, in the transition to adulthood and during adulthood itself. As the most frequently occurring form of ID worldwide, we use Down syndrome as a specific example of how diagnosing and treating SDB can lead to improved outcomes. CONCLUSIONS: This review highlights the importance of identifying SDB in this heterogenous population, recognising the multi-faceted, deleterious consequences of untreated SDB in people with ID, and presents some strategies that can be harnessed to improve diagnosis and management. Until further ID-specific research is available, we urge flexibility in the approach to people with ID and SDB based in guidelines and standard practice developed for the typically developing population.

Optical absorption and dichroism of single melanin nanoparticles.

Melanin nanoparticles (NPs) have important biological functions including photoprotection and colouration, and artificial melanin-like NPs are relevant for catalysis, drug delivery, diagnosis and therapy. Despite their importance, the optical properties of single melanin NPs have not been measured. We combine quantitative differential interference contrast (qDIC) and extinction microscopy to characterise the optical properties of single NPs, both naturally sourced from cuttlefish ink, as well as synthetic NPs using polydopamine (PDA) and L-3,4-dihydroxyphenylalanine (L-DOPA). Combining qDIC with extinction, we determine the absorption index of individual NPs. We find that on average the natural melanin NPs have a higher absorption index than the artificial melanin NPs. From the analysis of the polarisation-dependent NP extinction, the NP aspect ratio is determined, with mean values at 405 nm wavelength in agreement with transmission electron microscopy. At longer wavelengths, we observe an additional optical anisotropy which is attributed to dichroism by structural ordering of the melanin. Our quantitative analysis yields a dichroism of 2-10% of the absorption index, increasing with wavelength from 455 nm to 660 nm for L-DOPA and PDA. Such an in-depth quantification of the optical properties of single melanin NPs is important for the design and future application of these ubiquitous bionanomaterials.

The convexity condition of density-functional theory.

It has long been postulated that within density-functional theory (DFT), the total energy of a finite electronic system is convex with respect to electron count so that 2Ev[N0] ≤ Ev[N0 - 1] + Ev[N0 + 1]. Using the infinite-separation-limit technique, this Communication proves the convexity condition for any formulation of DFT that is (1) exact for all v-representable densities, (2) size-consistent, and (3) translationally invariant. An analogous result is also proven for one-body reduced density matrix functional theory. While there are known DFT formulations in which the ground state is not always accessible, indicating that convexity does not hold in such cases, this proof, nonetheless, confirms a stringent constraint on the exact exchange-correlation functional. We also provide sufficient conditions for convexity in approximate DFT, which could aid in the development of density-functional approximations. This result lifts a standing assumption in the proof of the piecewise linearity condition with respect to electron count, which has proven central to understanding the Kohn-Sham bandgap and the exchange-correlation derivative discontinuity of DFT.

The changing epidemiology of Neisseria gonorrhoeae genogroups and antimicrobial resistance in Queensland, Australia, 2010-15: a case series analysis of unique Neisseria gonorrhoeae isolates.

BACKGROUND: Neisseria gonorrhoeae (NG) can lead to serious reproductive and sexual health outcomes, and the annual number of NG notifications in Australia increased steadily from 10329 in 2010 to 29549 by 2020. Australian populations most affected are urban men who have sex with men and First Nations peoples living in remote areas, and a resurgence in urban heterosexuals has been observed since 2012. METHODS: A case series analysis of Queensland NG isolates (2010-15) exploring temporal trends and antimicrobial resistance by demographic and geographic distribution and genotype was performed. Proportions describe age, sex, strain, genogroup (NG multi-antigen sequence typing), region, swab site, antimicrobial sensitivity and isolate rates per 100000 population. Dominant genogroups were identified. RESULTS: Among 3953 isolates, the median age was 25years (IQR 20-34years) and most (n =2871/3915, 73%) were men. Brisbane city (68.8) and Far North Queensland (54.1) excluding Cairns showed the highest rates. Forty-six genogroups were documented, seven (G2992, G6876, G1415, G4186, G5, G1407 and G6937) comprised half of all isolates. The predominant male genogroup was G2992 (16%), and G6876 (20%) for females; G5 was predominantly male from 2010 to 2011, but equal in both sexes from 2012 to 2015. CONCLUSION: Considerable temporal, geographical and demographical diversity was observed in Queensland NG isolates, which has public health implications. Certain genogroups are more transient than others, and evidence suggests bridging from male-dominant networks to heterosexual networks. Molecular surveillance can enhance tracking the epidemiology and movement of NG in Australia, highlighting the necessity of genotyping to expose potentially prevalent strains circulating in undetected or underrepresented networks by current screening methods.

A Gonococcal Vaccine Has the Potential to Rapidly Reduce the Incidence of Neisseria gonorrhoeae Infection Among Urban Men Who Have Sex With Men.

BACKGROUND: A gonococcal vaccine is urgently needed due to increasing gonorrhea incidence and emerging multidrug-resistant gonococcal strains worldwide. Men who have sex with men (MSM) have among the highest incidences of gonorrhea and may be a key target population for vaccination when available. METHODS: An individual-based, anatomical site-specific mathematical model was used to simulate Neisseria gonorrhoeae transmission in a population of 10 000 MSM. The impact of vaccination on gonorrhea prevalence was assessed. RESULTS: With a gonococcal vaccine of 100% or 50% protective efficacy, gonorrhea prevalence could be reduced by 94% or 62%, respectively, within 2 years if 30% of MSM are vaccinated on presentation for sexually transmitted infection (STI) testing. Elimination of gonorrhea is possible within 8 years with vaccines of ≥ 50% efficacy lasting 2 years, providing a booster vaccination is available every 3 years on average. A vaccine's impact may be reduced if it is not effective at all anatomical sites. CONCLUSIONS: Our study indicates that with a vaccine of modest efficacy and an immunization strategy that targets MSM presenting for STI screening, the prevalence of gonorrhea in this population could be rapidly and substantially reduced.

Intensified partner notification and repeat testing can improve the effectiveness of screening in reducing Chlamydia trachomatis prevalence: a mathematical modelling study.

BACKGROUND: The Australian Chlamydia Control Effectiveness Pilot (ACCEPt) was a cluster randomised controlled trial designed to assess the effectiveness of annual chlamydia testing through general practice in Australia. The trial showed that testing rates increased among sexually active men and women aged 16-29 years, but after 3 years the estimated chlamydia prevalence did not differ between intervention and control communities. We developed a mathematical model to estimate the potential longer-term impact of chlamydia testing on prevalence in the general population. METHODS: We developed an individual-based model to simulate the transmission of Chlamydia trachomatis in a heterosexual population, calibrated to ACCEPt data. A proportion of the modelled population were tested for chlamydia and treated annually at coverage achieved in the control and intervention arms of ACCEPt. We estimated the reduction in chlamydia prevalence achieved by increasing retesting and by treating the partners of infected individuals up to 9 years after introduction of the intervention. RESULTS: Increasing the testing coverage in the general Australian heterosexual population to the level achieved in the ACCEPt intervention arm resulted in reduction in the population-level prevalence of chlamydia from 4.6% to 2.7% in those aged 16-29 years old after 10 years (a relative reduction of 41%). The prevalence reduces to 2.2% if the proportion retested within 4 months of treatment is doubled from the rate achieved in the ACCEPt intervention arm (a relative reduction of 52%), and to 1.9% if the partner treatment rate is increased from 30%, as assumed in the base case, to 50% (a relative reduction of 59%). CONCLUSION: A reduction in C. trachomatis prevalence could be achieved if the level of testing as observed in the ACCEPt intervention arm can be maintained at a population level. More substantial reductions can be achieved with intensified case management comprising retesting of those treated and treatment of partners of infected individuals.

Assessing the Impact of HIV Preexposure Prophylaxis Scale-Up on Gonorrhea Incidence Among Gay and Bisexual Men in Sydney: A Mathematical Modeling Study.

BACKGROUND: The rollout of preexposure prophylaxis (PrEP) for HIV prevention among gay and bisexual men (GBM) is associated with increases in condomless anal intercourse, potentially increasing the incidence of other sexually transmissible infections (STIs). METHODS: We developed an individual-based mathematical model to simulate the transmission of Neisseria gonorrhoeae among GBM in Sydney, accounting for changes in sexual practices, STI testing, and PrEP use. We calibrated and validated the model using reported incidence rates for HIV-positive and HIV-negative GBM from 2010 to 2019. Scenarios were run with varying PrEP uptake, PrEP-related STI testing, and PrEP-related sexual behavior and testing intervals up to 2030 to assess the impact of PrEP use on gonorrhea incidence. RESULTS: Preexposure prophylaxis uptake and associated 3-monthly STI testing from 2015 onward resulted in a predicted increase from 20 to 37 N. gonorrhoeae infections per 100 person-years among HIV-negative GBM by the end of 2020. This is lower than the counterfactual predictions of 45 per 100 person-years if PrEP were not scaled up and 48 per 100 person-years with nonadherence to 3-monthly STI testing. Increasing the time between STI tests for PrEP users by 1 month from 2018 results in the incidence rate among HIV-negative GBM increasing by 8% by 2030. If PrEP coverage doubles from 24% to 53%, incidence among HIV-negative GBM declines by ~25% by 2030. CONCLUSIONS: Behavior change due to widespread PrEP use may lead to significant increases in gonorrhea incidence in GBM, but the recommended quarterly STI testing recommended for PrEP users should reduce incidence by 18% by 2030.

Modelling response strategies for controlling gonorrhoea outbreaks in men who have sex with men in Australia.

The ability to treat gonorrhoea with current first-line drugs is threatened by the global spread of extensively drug resistant (XDR) Neisseria gonorrhoeae (NG) strains. In Australia, urban transmission is high among men who have sex with men (MSM) and importation of an XDR NG strain in this population could result in an epidemic that would be difficult and costly to control. An individual-based, anatomical site-specific mathematical model of NG transmission among Australian MSM was developed and used to evaluate the potential for elimination of an imported NG strain under a range of case-based and population-based test-and-treat strategies. When initiated upon detection of the imported strain, these strategies enhance the probability of elimination and reduce the outbreak size compared with current practice (current testing levels and no contact tracing). The most effective strategies combine testing targeted at regular and casual partners with increased rates of population testing. However, even with the most effective strategies, outbreaks can persist for up to 2 years post-detection. Our simulations suggest that local elimination of imported NG strains can be achieved with high probability using combined case-based and population-based test-and-treat strategies. These strategies may be an effective means of preserving current treatments in the event of wider XDR NG emergence.

Sizing individual dielectric nanoparticles with quantitative differential interference contrast microscopy.

We report a method to measure the size of single dielectric nanoparticles with high accuracy and precision using quantitative differential interference contrast (DIC) microscopy. Dielectric nanoparticles are detected optically by the conversion of the optical phase change into an intensity change using DIC. Phase images of individual nanoparticles were retrieved from DIC by Wiener filtering, and a quantitative methodology to extract nanoparticle sizes was developed. Using polystyrene beads of 100 nm radius as size standard, we show that the method determines this radius within a few nm accuracy. The smallest detectable polystyrene bead is limited by background and shot-noise, which depend on acquisition and analysis parameters, including the objective numerical aperture, the DIC phase offset, and the refractive index contrast between particles and their surrounding. Measurements on small beads of 15 nm nominal radius are shown, and a sensitivity limit potentially reaching down to 1.8 nm radius was inferred. As application example, individual nanodiamonds with nominal sizes below 50 nm were measured, and were found to have a nearly exponential size distribution with 28 nm mean value. Considering the importance of dielectric nanoparticles in many fields, from naturally occurring virions to polluting nanoplastics, the proposed method could offer a powerful quantitative tool for nanoparticle analysis, combining accuracy, sensitivity and high-throughput with widely available and easy-to-use DIC microscopy.

Modelling testing and response strategies for COVID-19 outbreaks in remote Australian Aboriginal communities.

BACKGROUND: Remote Australian Aboriginal and Torres Strait Islander communities have potential to be severely impacted by COVID-19, with multiple factors predisposing to increased transmission and disease severity. Our modelling aims to inform optimal public health responses. METHODS: An individual-based simulation model represented SARS-CoV2 transmission in communities ranging from 100 to 3500 people, comprised of large, interconnected households. A range of strategies for case finding, quarantining of contacts, testing, and lockdown were examined, following the silent introduction of a case. RESULTS: Multiple secondary infections are likely present by the time the first case is identified. Quarantine of close contacts, defined by extended household membership, can reduce peak infection prevalence from 60 to 70% to around 10%, but subsequent waves may occur when community mixing resumes. Exit testing significantly reduces ongoing transmission. Concurrent lockdown of non-quarantined households for 14 days is highly effective for epidemic control and reduces overall testing requirements; peak prevalence of the initial outbreak can be constrained to less than 5%, and the final community attack rate to less than 10% in modelled scenarios. Lockdown also mitigates the effect of a delay in the initial response. Compliance with lockdown must be at least 80-90%, however, or epidemic control will be lost. CONCLUSIONS: A SARS-CoV-2 outbreak will spread rapidly in remote communities. Prompt case detection with quarantining of extended-household contacts and a 14 day lockdown for all other residents, combined with exit testing for all, is the most effective strategy for rapid containment. Compliance is crucial, underscoring the need for community supported, culturally sensitive responses.

Long-term Outcomes Are Poor in Intravenous Drug Users Following Infective Endocarditis, Even After Surgery.

BACKGROUND: Previous studies of outcomes in people who inject drugs (PWID) with infective endocarditis (IE) have often been retrospective, have had small sample sizes, and the duration of follow-up has been short and limited to patients who were operated on. METHODS: PWID treated for IE between 1 January 2006 and 31 December 2016 were identified from a prospectively collected database. PWID hospitalized with other infections acted as a novel comparison group. Outcomes were all-cause mortality, cause of death, relapse, recurrence, and reoperation. RESULTS: There were 105 episodes of IE in 92 PWID and 112 episodes of other infections in 107 PWID in whom IE was suspected but rejected. Survival at 30 days for the IE group was 85%, and 30-day survival following surgery was 96%. The most common pathogens were Staphylococcus species (60%) and Streptococcus species (30%). The surgical intervention rate was 47%. Survival for the IE group at 1, 3, 5, and 10 years was 74%, 63%, 58%, and 44%, respectively. This was significantly lower compared with the comparator group of other infections in PWID (P = .0002). Mortality was higher in patients who required surgery compared with those who did not (hazard ratio, 1.8 [95% confidence interval, .95-3.3]). The commonest cause of death was infection (66%), usually a further episode of IE (55%). CONCLUSIONS: Although early survival was good, long-term life expectancy was low. This was attributable to ongoing infection risk, rather than other factors known to affect prognosis in PWID. Surgery conferred no long-term survival advantage. More efforts are needed to reduce reinfection risk following an episode of IE in PWID.While early survival for people who inject drugs (PWID) with infective endocarditis is good, long-term survival is poor due to ongoing infection risk. Surgery conferred no long-term survival advantage, so more efforts are needed to reduce reinfection risks for PWID.

Quantitative Label-Free Imaging of Lipid Domains in Single Bilayers by Hyperspectral Coherent Raman Scattering.

Lipid phase separation in cellular membranes is thought to play an important role in many biological functions. This has prompted the development of synthetic membranes to study lipid-lipid interactions in vitro, alongside optical microscopy techniques aimed at directly visualizing phase partitioning. In this context, there is a need to overcome the limitations of fluorescence microscopy, where added fluorophores can significantly perturb lipid packing. Raman-based optical imaging is a promising analytical tool for label-free chemically specific microscopy of lipid bilayers. In this work, we demonstrate the application of hyperspectral coherent Raman scattering microscopy combined with a quantitative unsupervised data analysis methodology developed in-house to visualize lipid partitioning in single planar membrane bilayers exhibiting liquid-ordered and liquid-disordered domains. Two home-built instruments were utilized, featuring coherent anti-Stokes Raman scattering and stimulated Raman scattering modalities. Ternary mixtures of dioleoylphosphatidylcholine, sphingomyelin, and cholesterol were used to form phase-separated domains. We show that domains are consistently resolved, both chemically and spatially, in a completely label-free manner. Quantitative Raman susceptibility spectra of the domains are provided alongside their spatially resolved concentration maps.

Supplemental Trichomonas vaginalis testing is required to maintain control following a transition from Pap smear to HPV DNA testing for cervical screening: a mathematical modelling study.

OBJECTIVES: Using mathematical modelling, we have previously shown that the prevalence of infection with Trichomonas vaginalis (TV) is likely to increase in the general population in Australia with the transition from Pap smear-based cervical screening to human papillomavirus (HPV) DNA testing. Here we use the existing model to estimate the level of supplemental testing required to maintain TV control. METHODS: A compartmental mathematical model describing the transmission of TV in the general heterosexual population in Australia was used to evaluate the impact of a range of screening scenarios on TV prevalence over time following the transition to HPV DNA testing for cervical screening. Scenarios considered were the inclusion of a TV test with the HPV test and the addition of TV testing to routine chlamydia testing conducted in primary care. RESULTS: Our modelling suggests that with sufficient coverage, inclusion of TV testing with routine chlamydia screening in general practice, TV prevalence can be reduced over time, but at the current reported coverage will gradually increase following the transition to HPV testing. Inclusion of TV testing with HPV testing in the cervical screening programme is preferable to no supplemental testing but is considerably less effective in controlling TV. CONCLUSIONS: These findings support the inclusion of TV testing with routine chlamydia testing of young people.

Factors Associated With Early Resumption of Condomless Anal Sex Among Men Who Have Sex With Men After Rectal Chlamydia Treatment.

BACKGROUND: The resumption of sexual activity shortly after commencing treatment for sexually transmitted infections (STIs) is poorly described despite contributing to onward transmission. With azithromycin remaining an option for rectal Chlamydia trachomatis, resuming sex too early after treatment may contribute to antimicrobial resistance because of exposure of newly acquired STIs to subinhibitory concentrations. METHODS: Clinical and sexual behavioral data were collected from men participating in a trial assessing treatment efficacy for rectal chlamydia. Data were collected at recruitment and weekly for 3 weeks after commencing treatment. Outcome measures were resumption of any sexual activity or condomless receptive anal sex within 1, 2, or 3 weeks after commencing treatment. Generalized linear regression was used to calculate adjusted risk ratios (aRR) to identify associated factors. RESULTS: Almost 1 in 10 men (9.5%; 95% confidence interval [CI], 7.2-12.1) resumed condomless receptive anal sex within 1 week of commencing treatment. This was associated with current preexposure prophylaxis use (aRR, 3.4; 95% CI, 2.5-4.8]) and having 9 or more sexual partners in the last 3 months (aRR, 3.2; 95% CI, 1.6-5.0). Most men (75.0%; 95% CI, 71.3-78.5) resumed any sexual activity within 3 weeks; this was associated with a greater number of sexual partners (4-8 partners; aRR, 1.2; 95% CI, 1.1-1.5; ≥9 partners; aRR, 1.5; 95% CI, 1.3-1.7). CONCLUSIONS: Resuming condomless receptive anal sex early after treatment may facilitate onward transmission and promote antimicrobial resistance for STIs. Although azithromycin remains a treatment option, this analysis highlights the need for new health promotion messages regarding early resumption of sex and continued surveillance for antimicrobial resistance.

The ONETEP linear-scaling density functional theory program.

We present an overview of the onetep program for linear-scaling density functional theory (DFT) calculations with large basis set (plane-wave) accuracy on parallel computers. The DFT energy is computed from the density matrix, which is constructed from spatially localized orbitals we call Non-orthogonal Generalized Wannier Functions (NGWFs), expressed in terms of periodic sinc (psinc) functions. During the calculation, both the density matrix and the NGWFs are optimized with localization constraints. By taking advantage of localization, onetep is able to perform calculations including thousands of atoms with computational effort, which scales linearly with the number or atoms. The code has a large and diverse range of capabilities, explored in this paper, including different boundary conditions, various exchange-correlation functionals (with and without exact exchange), finite electronic temperature methods for metallic systems, methods for strongly correlated systems, molecular dynamics, vibrational calculations, time-dependent DFT, electronic transport, core loss spectroscopy, implicit solvation, quantum mechanical (QM)/molecular mechanical and QM-in-QM embedding, density of states calculations, distributed multipole analysis, and methods for partitioning charges and interactions between fragments. Calculations with onetep provide unique insights into large and complex systems that require an accurate atomic-level description, ranging from biomolecular to chemical, to materials, and to physical problems, as we show with a small selection of illustrative examples. onetep has always aimed to be at the cutting edge of method and software developments, and it serves as a platform for developing new methods of electronic structure simulation. We therefore conclude by describing some of the challenges and directions for its future developments and applications.

How to stich? 90 degrees: The perfect angle.

OBJECTIVE: This is a discussion about correct suturing techniques and implications that follow inappropriate suturing. We deconstruct the suturing needle angles and methods to be adopted to acquire the perfect needle angle to the tissue being sutured. A study of angles confirms that 90° is perceptible to the naked eye and easy to identify, making it an appropriate foundation to explain, communicate and teach the concepts in the wet-lab and the operating room. BACKGROUND: There is a lack of robust teaching regarding entry of the needle orthogonal to the tissue planes. In addition, objective methods of assessing angles of the needle relative to the tissue and consequences of inaccuracy are lacking. The authors aim to deconstruct the steps of suturing with the aim of demonstrating ninety degrees is the perfect suturing angle. STUDY DESIGN: We conducted a study to identify 90° (the perfect suturing angle) as an angle easy to identify with the naked eye. Angles from 86° to 94° and 41° to 49° were printed and presented to volunteers with the instruction to identify the angles of 90° and 45°. RESULTS: Fifty-one volunteers replied to the 90° angle study and sixty-five volunteers replied to the 45° study. 92% correctly identified at least one 90° angle and 72% identified both the 90° angles. 63% identified at least one 45° angle and only 27% identified both the 45° angles presented to them. This supported our hypothesis that 90° is an angle that is readily identifiable to the human eye. CONCLUSIONS: Objective assessment of surgical skills and training should focus on the basic needle skills with particular emphasis on suturing angles, progressing to higher skills using low and intermediate fidelity models and correlating practice alongside the trainees' operative progress.

Population effectiveness of opportunistic chlamydia testing in primary care in Australia: a cluster-randomised controlled trial.

BACKGROUND: Screening young adults who are sexually active for genital Chlamydia trachomatis infection is promoted in several high-income countries, but its effectiveness at the population level is highly debated. We aimed to investigate the effects of opportunistic chlamydia testing in primary care on the estimated chlamydia prevalence in the population aged 16-29 years in Australia. METHODS: We did a cluster-randomised controlled trial. Clusters were rural towns with a minimum of 500 women and men aged 16-29 years and no more than six primary care clinics. We randomly allocated each cluster using a computer-generated minimisation algorithm to receive a multifaceted, clinic-based chlamydia testing intervention or to continue usual care. The intervention included computerised reminders to test patients, an education package, payments for chlamydia testing, and feedback on testing rates. The primary outcome was chlamydia prevalence, estimated before randomisation (survey 1) and at the end of the trial (survey 2) in patients aged 16-29 years who attended the clinics. Analyses were done by intention to treat. General practitioners and clinic staff were aware of group allocation, whereas patients and laboratory staff who performed the chlamydia tests were not. This trial was completed on Dec 31, 2015, and is registered (ACTRN12610000297022). FINDINGS: Between Dec 14, 2010, and Sept 14, 2015, 26 clusters (63 clinics) received the chlamydia testing intervention and 26 (67 clinics) continued usual care. Over a mean duration of 3·1 years (SD 0·3), 93 828 young adults attended intervention clinics and 86 527 attended control clinics. The estimated chlamydia prevalence decreased from 5·0% (95% CI 3·8 to 6·2) at survey 1 to 3·4% (2·7 to 4·1) at survey 2 in the intervention clusters (difference -1·6%, 95% CI -2·9 to -0·3) and from 4·6% (95% CI 3·5 to 5·7) at survey 1 to 3·4% (2·4 to 4·5) at survey 2 in the control clusters (difference -1·1%, -2·7 to 0·5). The unadjusted odds ratio for the difference between intervention and control clusters was 0·9 (95% CI 0·5 to 1·5). INTERPRETATION: These findings, in conjunction with evidence about the feasibility of sustained uptake of opportunistic testing in primary care, indicate that sizeable reductions in chlamydia prevalence might not be achievable. FUNDING: Australian Government Department of Health, National Health and Medical Research Council, Victorian Department of Health and Human Services, and New South Wales Ministry of Health.

Modelling the decline and future of hepatitis A transmission in Australia.

Hepatitis A incidence has declined in most countries through a combination of prevention measures, augmented through the use of a highly effective vaccine. In Australia, the proportion of the population susceptible to hepatitis A infection has declined over time due to high rates of opportunistic vaccination as well as the sustained inflow of seropositive immigrants from high-endemicity countries. These factors have contributed to a rapid decline in incidence. An age-structured hepatitis A transmission model incorporating demographic changes was fitted to seroprevalence and disease notification data and used to project incidence trends and transmission potential for hepatitis A in the general population. Robustness of findings was assessed through worst-case scenarios regarding vaccine uptake, migration and the duration of immunity. The decline in age-specific seroprevalence until the introduction of hepatitis A vaccine in 1994 was well explained through a declining basic reproduction number (R0 ) that remained >1. Accounting for existing immunity, we estimated that the effective reproduction number (Reff ) <1 in the general population of Australia since the early 1990s, declining more rapidly after the introduction of the hepatitis A vaccine. Future projections under a variety of scenarios support Reff remaining <1 with continued low incidence in the general population. In conclusion, our results suggest that sustained endemic transmission in the general Australian population is no longer possible although risks of sporadic outbreaks remain. This suggests potential for local elimination of hepatitis A infection in Australia, provided that elimination criteria can be defined and satisfied in risk groups. The methodology used here to investigate elimination potential can easily be replicated in settings such as in the USA where sequential seroprevalence studies are supported by routine notification data.

Lipid Bilayer Thickness Measured by Quantitative DIC Reveals Phase Transitions and Effects of Substrate Hydrophilicity.

Quantitative differential interference contrast microscopy is demonstrated here as a label-free method, which is able to image and measure the thickness of lipid bilayers with 0.1 nm precision. We investigate the influence of the substrate on the thickness of fluid-phase 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)-supported lipid bilayers and find a thinning of up to 10%, depending on substrate hydrophilicity, local bilayer coverage, and ionic strength of the medium. With fluorescently labeled lipid bilayers, we also observe changes in the bilayer thickness depending on the choice of fluorophore. Furthermore, liquid-ordered domains in bilayers, formed from DOPC, cholesterol, and sphingomyelin, are measured, and the corresponding thickness change between the liquid-ordered and liquid-disordered phases is accurately determined. Again, the thickness difference is found to be dependent on the presence of the fluorophore label, highlighting the need for quantitative label-free techniques.