Search

Gay and bisexual men (GBM) who use pre-exposure prophylaxis (PrEP) are at increased risk of sexually transmitted infections (STIs) compared to those who don't use PrEP. Since the implementation of PrEP in Australia, it is possible that attitudes towards STIs have shifted in line with changes in risk and transmission dynamics in the context of increased screening. As the extent to which GBM utilise STI prevention strategies likely depends on their attitudes towards STIs and STI prevention, the aims of this study were to use latent class analysis (LCA) to classify GBM using PrEP on the basis of their attitudes towards STIs and reported risk behaviours, and examine how these categorisations relate to risk of STI acquisition. 1225 GBM who were previously enrolled in a PrEP implementation study (The PrEPX Study) completed a survey focused on sexual behaviours and attitudes towards STIs 1 year post-study follow-up. Data on chlamydia, gonorrhoea and syphilis testing and positivity were available through a sentinel network of participating study clinics. Using LCA, participants were allocated into four classes; Class 1, "Some concern and lowest risk"; Class 2, "Low concern and lower risk"; Class 3, " High concern and higher risk"; and Class 4, "Low concern and highest risk". The majority (78%) of participants were classified into Class 3 or Class 4, two groups which were distinguished by highly disparate attitudes towards STIs but with a similar proportion of participants diagnosed with a bacterial STI in the last 12 months (48% and 57%, respectively). Findings suggest that attitudes towards STIs among GBM using PrEP in Australia vary considerably, and this will likely influence their receptivity to different STI prevention strategies.

In 2020, school and early childhood educational centre (ECEC) closures affected over 1.5 billion school‐aged children globally as part of the COVID‐19 pandemic response. Attendance at school and access to ECEC is critical to a child's learning, well‐being and health. School closures increase inequities by disproportionately affecting vulnerable children. Here, we summarise the role of children and adolescents in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) transmission and that of schools and ECECs in community transmission and describe the Australian experience. In Australia, most SARS‐CoV‐2 cases in schools were solitary (77% in NSW and 67% in Victoria); of those that did progress to an outbreak, >90% involved fewer than 10 cases. Australian and global experience has demonstrated that SARS‐CoV‐2 is predominantly introduced into schools and ECECs during periods of heightened community transmission. Implementation of public health mitigation strategies, including effective testing, tracing and isolation of contacts, means schools and ECECs can be safe, not drivers of transmission. Schools and ECEC are essential services and so they should be prioritised to stay open for face‐to‐face learning. This is particularly critical as we continue to manage the next phase of the COVID‐19 pandemic.

Background The aim of this review is to explore acceptability, barriers, and facilitators to PrEP use among African migrants in high-income countries. Methods: A systematic review was conducted to explore reasons that contribute to low PrEP uptake in this population. Three online databases, abstracts from key conferences and reference lists of relevant studies articles published between the 2 July 2018 and 3 March 2019 were searched. Narrative synthesis was performed on quantitative data and thematic synthesis was performed on qualitative data. Results: Of 1779 titles retrieved, two cross-sectional studies (United States (US) (n = 1), United Kingdom (UK) (n = 1)) and six qualitative studies (US (n = 2), UK (n = 3), Australia (n = 1)) met inclusion criteria. PrEP acceptability was reported in one cross-sectional article and two qualitative articles. Cross-sectional studies measured acceptability and willingness to use PrEP; in one study, 46% of African migrant men found PrEP use acceptable, and following PrEP education, another study categorised 60% of participants as willing to use PrEP if it were cost-free. Qualitative studies reported mixed acceptability, with higher acceptability reported for serodiscordant couples. Barriers and facilitators to PrEP use were coded into five themes: cultural aspects of stigma; knowledge gap in health literacy; risks unrelated to HIV transmission; practical considerations for PrEP use; and the impact of PrEP use on serodiscordant couples. Conclusions: Several common barriers to PrEP use, including stigma, health literacy and risk perception and cost, were identified. Findings were limited by there being no published data on uptake. Additional work is needed to understand PrEP acceptability and uptake among African migrants.

Rapid scale-up of preexposure prophylaxis resulted in a redistribution of human immunodeficiency virus and sexually transmitted infection testing across services in Victoria, Australia and did not negatively impact testing among gay and bisexual and other men who have sex with men not using preexposure prophylaxis., Objective Scale-up of human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) has raised concerns regarding its impact on clinic capacity and access to HIV testing. We describe enrolment in PrEPX, a large PrEP implementation study in Victoria, Australia, and the impact of PrEP uptake and maintenance on existing health services. Methods We describe enrolment between July 26, 2016, and March 31, 2018, and trends in HIV testing among PrEPX participating and nonparticipating gay and bisexual and other men who have sex with men (GBM) at 5 study clinics participating in a sentinel surveillance system (ACCESS). We evaluated HIV and STI testing trends using segmented linear regression across the prestudy (January 2015 to June 2016) and PrEPX study (July 2016 to March 2018) periods. Findings There were 2,049 individuals who registered interest in study participation: 72% enrolled into the study. Study clinics enrolled participants rapidly; of 4265 people enrolled in PrEPX (98% GBM), 1000 enrolled by week 3, 88% (n = 876) of whom enrolled at ACCESS sites. Prestudy period HIV testing rates were increasing at all ACCESS sites. In the month PrEPX commenced, there was an additional 247 HIV tests among PrEPX participants (P < 0.01) and no significant change among non-PrEPX GBM (P = 0.72). Across the study period, HIV testing increased by 7.2 (P < 0.01) and 8.9 (P < 0.01) tests/month among PrEPX participants and non-PrEPX GBM, respectively. The HIV testing increased among non-PrEPX GBM at sexual health clinics (18.8 tests/month, P < 0.01) and primary care clinics (7.9 tests/month, P < 0.01). Similar trends were observed across testing for all measured STIs. Conclusions Rapid PrEP scale-up is possible without a reduction in HIV testing among GBM not using PrEP.

Gay and bisexual men (GBM) who use pre-exposure prophylaxis (PrEP) are at increased risk of sexually transmitted infections (STIs) compared to those who don't use PrEP. Since the implementation of PrEP in Australia, it is possible that attitudes towards STIs have shifted in line with changes in risk and transmission dynamics in the context of increased screening. As the extent to which GBM utilise STI prevention strategies likely depends on their attitudes towards STIs and STI prevention, the aims of this study were to use latent class analysis (LCA) to classify GBM using PrEP on the basis of their attitudes towards STIs and reported risk behaviours, and examine how these categorisations relate to risk of STI acquisition. 1225 GBM who were previously enrolled in a PrEP implementation study (The PrEPX Study) completed a survey focused on sexual behaviours and attitudes towards STIs 1 year post-study follow-up. Data on chlamydia, gonorrhoea and syphilis testing and positivity were available through a sentinel network of participating study clinics. Using LCA, participants were allocated into four classes; Class 1, "Some concern and lowest risk"; Class 2, "Low concern and lower risk"; Class 3, " High concern and higher risk"; and Class 4, "Low concern and highest risk". The majority (78%) of participants were classified into Class 3 or Class 4, two groups which were distinguished by highly disparate attitudes towards STIs but with a similar proportion of participants diagnosed with a bacterial STI in the last 12 months (48% and 57%, respectively). Findings suggest that attitudes towards STIs among GBM using PrEP in Australia vary considerably, and this will likely influence their receptivity to different STI prevention strategies.

Whilst the testing and treatment of people who inject drugs (PWID) in Australia is a priority for local hepatitis C (HCV) elimination efforts, perceived stigma related to injecting drug use (IDU) has been identified as a major barrier for PWID engaging in health services. We used data from the EC Experience cohort study to explore associations between IDU-related perceived stigma and the number of different health services accessed by PWID in Melbourne, Australia. Data from the baseline questionnaire were used. Primary outcome was self-reported experience of stigma due to IDU (never, rarely, sometimes, often, always) in the previous 12 months. An ordinal logistic regression model assessed the association between stigma experienced and the number of different health services used (1-2, 3-4, 5-6, 7-10 different services) adjusted for recent IDU and key socio-demographics. Between September 2018 and February 2020, 281 participants were recruited from four health services. Sixty-nine per cent were male, median age was 42, 83% reported past-month IDU, 34% had never tested/tested >12 months, 8% tested negative

Posture, a potentially modifiable injury risk factor, is considered important in injury screening/prevention in athletes, yet few studies investigate relationships between posture and injury. This prospective cohort study investigated whether static posture is associated with lower limb injury risk in male football players (n = 263). Nine aspects of static standing posture (left and right rearfoot, knee interspace, lateral knee, lumbar lordosis, thoracic kyphosis, scoliosis S and C, forward head) were assessed from photographs during the pre-season using the modified Watson and Mac Donncha scale, which was dichotomised for analysis (deviated or normal). Player characteristics (age, height, mass, body mass index, competition level), match/training exposure, and previous and in-season non-contact lower limb injuries were recorded. Binary logistic regression investigated relationships between posture and injury (previous and in-season). Eighty previous and 24 in-season lower limb injuries were recorded. Previous injury was not associated with any postural variable. In-season injury was associated with previous injury (OR = 3.04, 95% CI 1.20–7.68, p = 0.02) and having a normal thoracic curve compared to kyphosis (OR = 0.38, 95% CI 0.15–1.00, p = 0.05) but no other postural variables. Static postural deviations observed in male football players in the pre-season are not typically associated with non-contact lower limb injury risk, thus, they are unlikely to add value to pre-season screening programs.

Background Although HIV self-tests can support frequent HIV testing, their impact on attending clinics for other sexually transmissible infection (STI) testing and sexual health care is largely unknown. We explored intentions to use HIV self-tests and how this might affect patterns of attending sexual health services among gay, bisexual, and other men who have sex with men (GBM) in Victoria, Australia. Methods Gay, bisexual, and other men who have sex with men self-completed an online survey between March 10 and June 10, 2019. Among GBM reporting lifetime HIV testing and intentions to self-test at least once annually, we used logistic regression to identify correlates of intending to replace clinic-based HIV testing with self-tests. Qualitative interviews with purposively selected survey participants undertaken between May and June 2019 explored the implications of self-testing on clinic-based sexual health care. Results Of the 279 survey participants, 79 (29%) reported they would replace most or all clinic-based HIV tests with self-tests, with longer time since last testing for HIV and younger age associated with reporting this outcome in the multivariate analysis. Qualitative interviews revealed different perceived roles for self-tests and clinic-based testing, and the importance of integrating HIV self-tests within broader sexual health routines. Conclusions Although GBM see a distinct role for HIV self-testing, its rollout will likely result in missed opportunities for clinic-based STI testing and education for some GBM, particularly among younger and less-recently tested GBM. Convenient, non-clinic-based approaches to STI testing are needed alongside support platforms to maximize the benefits of HIV self-testing within comprehensive sexual health routines.

Background HIV continues to disproportionately affect men who have sex with men (MSM) and transgender women (TW). Undiagnosed HIV is a major driver of HIV transmission rates, and increasing the uptake of regular HIV testing and facilitating timely initiation of HIV treatment is a global HIV prevention priority. However, MSM and TW experience a range of barriers that limit their access to testing and other prevention services. Given their growing ubiquity, digital communication technologies are increasingly being used to support HIV prevention efforts, and a growing number of studies have trialed the use of digital technology to promote HIV testing among MSM and TW. Objective We undertook a systematic review and meta-analysis to assess the impact of digital communication technology on HIV testing uptake among MSM and TW. Subanalyses aimed to identify the features and characteristics of digital interventions associated with greater impact. Methods A systematic literature review was undertaken using select databases and conference repositories. Studies describing the use of a digital technology—internet-enabled devices, including phones, tablets, and computers—to increase HIV testing uptake among MSM or TW using either randomized or observational cohort design with measurement of HIV testing rates measured pre- and postintervention, and published in English between 2010 and 2018 were included. Pooled effect estimates were calculated using a random effects meta-analysis. Subanalyses calculated effect estimates grouped by selected features of digital interventions. Results A total of 13 randomized or observational studies were included in the final review. Digital interventions most commonly used mainstream, existing social media platforms (n=7) or promotion through online peer educators (n=5). Most interventions (n=8) were categorized as interactive and allowed user engagement and most directly facilitated testing (n=7) either by providing self-testing kits or referral to testing services. A total of 1930 participants were included across the 13 studies. HIV testing uptake among MSM and TW exposed to digital interventions was 1.5 times higher than that of unexposed MSM and TW (risk ratio [RR] 1.5; 95% CI 1.3-1.7). Subanalyses suggested an increased impact on HIV testing uptake among interventions that were delivered through mainstream social media–based platforms (RR 1.7; 95% CI 1.3-2.1), included direct facilitation of HIV testing (RR 1.6; 95% CI 1.4-1.9), were interactive (RR 1.6; 95% CI 1.4-1.8), and involved end users in the design process (RR 1.6; 95% CI 1.3-2.0). Conclusions These findings provide broad support for the integration of technology with existing approaches to promote and facilitate HIV testing among MSM and TW. Our findings identified key features that may be associated with greater impact on HIV testing uptake and can be used to inform future development efforts given the growing interest and application of digital technologies in HIV prevention. Trial Registration PROSPERO International Prospective Register of Systematic Reviews CRD42017070055; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017070055.

Background Reliably measuring drug use by gay, bisexual and other men who have sex with men (GBM) in the context of sex can inform sexual health service responses. We report changing drug use patterns among GBM testing for HIV at a community-based service in Melbourne in response to behavioural survey modifications. Methods Surveys were completed by GBM prior to all HIV tests. Survey one asked about use of "party drugs for the purpose of sex" and survey two asked about specific drug use (alcohol, amyl nitrate, methamphetamine, cocaine, ecstasy, GHB, Viagra ® /Cialis ® ) before or during sex. Differences in drug use prevalence and demographic and sexual risk correlates are reported. Results Reported drug use increased from 16.9% in survey one to 54.0% in survey two. Among GBM completing both surveys, 45% who reported no drug use in survey one reported drug use in survey two. Drug use was associated with high HIV risk behaviours across both surveys. Conclusion Survey modification improved ascertainment of drug use in the context of sex among GBM. Continued monitoring of drug use in this setting will improve our understanding the relationship between use of specific drugs and sexual health and help inform client focused health promotion.

Frequent HIV testing among gay, bisexual and other men who have sex with men (GBM) is a strategic priority for HIV prevention in Australia. To overcome barriers to testing in conventional clinical services, Australia recently introduced peer HIV rapid point of care (RPOC) testing services for GBM. This mixed methods evaluation describes client acceptability and HIV prevention benefits of a peer HIV testing model. Most aspects of the service model were overwhelmingly acceptable to clients. Two-thirds of survey participants reported preferring testing with peers rather than doctors or nurses and over half reported learning something new about reducing HIV risk. Focus group findings suggested peer-delivered HIV RPOC testing reduced stigma-related barriers to frequent testing and provided novel opportunities for GBM to openly discuss HIV prevention and sexual practices, enhancing their HIV risk-reduction knowledge. Analysis of survey data suggested knowledge transfer occurred particularly among younger and less gay community-attached GBM.

Introduction Achieving the virtual elimination of HIV requires equitable access to HIV prevention tools for all priority populations. Restricted access to healthcare means migrants face particular barriers to HIV prevention services. In February 2016, a peer‐led rapid HIV testing service for gay, bisexual and other men who have sex with men (gay and bisexual men, GBM) in Melbourne, Australia, introduced free sexually transmissible infection (STI) testing funded through Medicare (Australia's universal healthcare system). Medicare ineligible migrant clients were required to pay up to $158AUD for STI tests. We determined the uptake of STI testing and assessed the impact on repeat HIV testing among Medicare eligible and ineligible clients. Methods All HIV tests conducted between August 2014 and March 2018 were included. We describe client characteristics, STI testing uptake and HIV/STI positivity among Medicare eligible and ineligible clients. Repeat HIV testing, assessed as the percentage of HIV tests with a return test within six months, was compared pre‐integration (August 2014‐June 2016) and post‐integration(July 2016‐March 2018) of STI testing using segmented linear regression of monthly aggregate data for Medicare eligible and ineligible clients. Results Analyses included 9134 HIV tests among 4753 individuals. Medicare ineligible clients were younger (p

We surveyed 970 PrEPX study participants to evaluate interest in switching from daily to on-demand PrEP in a study setting. Interested respondents (n = 469, 48%) more commonly reported PrEP cessation (adjusted odds ratio [aOR], 3.0; P < .001), difficulty with adherence (aOR, 1.6; P = .029), infrequent sex (aOR, 3.7; P < .001), and toxicity concerns (aOR, 2.7; P < .001).

Importance Emerging evidence suggests that risk of bacterial sexually transmitted infections (STIs) increases among gay and bisexual men following initiation of HIV preexposure prophylaxis (PrEP). Objective To describe STI incidence and behavioral risk factors among a cohort of predominantly gay and bisexual men who use PrEP, and to explore changes in STI incidence following PrEP commencement. Design, Setting, and Participants The Pre-exposure Prophylaxis Expanded (PrEPX) Study, a multisite, open-label intervention study, was nested within the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) clinic network. A total of 4275 participants were enrolled (July 26, 2016–April 1, 2018) in Victoria, Australia. Of these, 2981 enrolled at 5 ACCESS clinics (3 primary care, 1 sexual health, and 1 community-based HIV rapid testing service), had at least 1 follow-up visit, and were monitored until April 30, 2018. Exposures Upon enrollment, participants received daily oral tenofovir disoproxil fumurate and emtricitabine for HIV PrEP, quarterly HIV and STI testing, and clinical monitoring. Main Outcomes and Measures The primary outcome was incidence of chlamydia, gonorrhea, or syphilis. Incidence rates and hazard ratios describing behavioral risk factors of STI diagnosis were calculated. Incidence rate ratios (IRRs), adjusted for change in testing frequency, described changes in STI incidence from 1-year preenrollment to study follow-up among participants with preenrollment testing data (n = 1378). Results Among the 2981 individuals (median age, 34 years [interquartile range, 28-42]), 98.5% identified as gay or bisexual males, 29% used PrEP prior to enrollment, 89 (3%) withdrew and were censored at date of withdrawal, leaving 2892 (97.0%) enrolled at final follow-up. During a mean follow-up of 1.1 years (3185.0 person-years), 2928 STIs were diagnosed among 1427 (48%) participants (1434 chlamydia, 1242 gonorrhea, 252 syphilis). STI incidence was 91.9 per 100 person-years, with 736 participants (25%) accounting for 2237 (76%) of all STIs. Among 2058 participants with complete data for multivariable analysis, younger age, greater partner number, and group sex were associated with greater STI risk, but condom use was not. Among 1378 participants with preenrollment testing data, STI incidence increased from 69.5 per 100 person-years prior to enrollment to 98.4 per 100 person-years during follow-up (IRR, 1.41 [95% CI, 1.29-1.56]). After adjusting for testing frequency, the increase in incidence from 1 year preenrollment to follow-up was significant for any STI (adjusted IRR, 1.12 [95% CI, 1.02-1.23]) and for chlamydia (adjusted IRR, 1.17 [95% CI, 1.04-1.33]). Conclusions and Relevance Among gay and bisexual men using PrEP, STIs were highly concentrated among a subset, and receipt of PrEP after study enrollment was associated with an increased incidence of STIs compared with preenrollment. These findings highlight the importance of frequent STI testing among gay and bisexual men using PrEP.

Objective: PRONTO!, a peer‐led rapid HIV‐testing service in Melbourne, Australia, opened to improve HIV testing among gay and bisexual men (GBM). We compared client characteristics and return testing among GBM testing at PRONTO! with GBM testing at Melbourne Sexual Health Centre (MSHC). Methods: All GBM attending PRONTO! and MSHC for HIV testing between August 2013 and April 2016 were included. We describe the number of tests, percentage of clients who returned during follow‐up, the mean number of tests and median time between tests at the two services. Results: At PRONTO!, 33% of 3,102 GBM and at MSHC 50% of 9,836 GBM returned for a further HIV test at least once. The mean number of tests per client was 1.7 and 2.5 at PRONTO! and MSHC (p

Objective: To develop an HIV response suited to women and to inform appropriate services, we describe the characteristics of women diagnosed and living with HIV using 22 years of high‐quality surveillance data. Methods: Data on women newly diagnosed with HIV between 1994 and 2016 and women living with diagnosed HIV in Victoria at 31 December 2016 were extracted from the Victorian Public Health Surveillance System. Descriptive analysis by place of birth was performed and Poisson regression used to assess trends over time. Results: There were 465 new diagnoses among women in Victoria between 1994 and 2016 and 613 women living with HIV in 2016. Women were diagnosed late, and frequently reported no HIV testing history, AIDS‐defining illness or other symptoms of HIV at diagnosis. These indicators of delayed diagnosis were even greater for non‐Australian‐born women. Conclusions and implications for public health: For Victoria to reach the ambitious targets for diagnosis, treatment and viral suppression in 95% of people living with HIV, prevention programs and efforts to increase early diagnosis as well as support services must consider the epidemiology and diversity of women.

Molecular simulation is a powerful tool for studying the nanotribology of single-asperity contacts, but computational limits require that compromises be made when choosing tip sizes. To assess and correct for the finite size effects, complementary finite element (FE) and molecular statics (MS) simulations examining the effects of tip size (height and radius) on contact stiffness and stress were performed. MS simulations of contact between paraboloidal tips and a flat, rigid diamond substrate using the 2B-SiCH reactive empirical bond-order potential were used to generate force–displacement curves and stress maps. Tips of various radii and heights, truncated by a rigid boundary, were formed from carbon- and silicon-containing materials so that they possessed differing elastic properties. Results were compared to FE simulations with matching geometries and elastic properties. FE analysis showed that the rigid boundary at the back of the tip influences the contact stiffness strongly, deviating from the Hertz model for small tip heights and radii. By examining the relationships between force, tip height, tip radii, and elastic properties obtained with FE simulations, a map interpolation method is presented that accounts for the effect of tip size and enables the extraction of Young’s modulus from MS force–displacement data. Furthermore, the FE results show that the effect of the finite size of the tip on contact stress is less pronounced than its effect on stiffness. The MS simulations also demonstrate that stress propagation within the tip is significantly impacted by the structure of the tip.

The work of adhesion is an interfacial materials property that is often extracted from atomic force microscope (AFM) measurements of the pull-off force for tips in contact with flat substrates. Such measurements rely on the use of continuum contact mechanics models, which ignore the atomic structure and contain other assumptions that can be challenging to justify from experiments alone. In this work, molecular dynamics is used to examine work of adhesion values obtained from simulations that mimic such AFM experiments and to examine variables that influence the calculated work of adhesion. Ultrastrong carbon-based materials, which are relevant to high-performance AFM and nano- and micromanufacturing applications, are considered. The three tips used in the simulations were composed of amorphous carbon terminated with hydrogen (a-C-H), and ultrananocrystalline diamond with and without hydrogen (UNCD-H and UNCD, respectively). The model substrate materials used were amorphous carbon with hydrogen termination (a-C-H) and without hydrogen (a-C); ultrananocrystalline diamond with (UNCD-H) and without hydrogen (UNCD); and the (111) face of single crystal diamond with (C(111)-H) and without a monolayer of hydrogen (C(111)). The a-C-H tip was found to have the lowest work of adhesion on all substrates examined, followed by the UNCD-H and then the UNCD tips. This trend is attributable to a combination of roughness on both the tip and sample, the degree of alignment of tip and substrate atoms, and the surface termination. Continuum estimates of the pull-off forces were approximately 2-5 times larger than the MD value for all but one tip-sample pair.

The effect of atomic-scale roughness on adhesion between carbon-based materials is examined by both simulations and experimental techniques. Nanoscale asperities composed of either diamond-like carbon or ultrananocrystalline diamond are brought into contact and then separated from diamond surfaces using both molecular dynamics simulations and in situ transmission electron microscope (TEM)-based nanoindentation. Both techniques allow for characterization of the roughness of the sharp nanoasperities immediately before and after contact down to the subnanometer scale. The root mean square roughness for the simulated tips spanned 0.03 nm (atomic corrugation) to 0.12 nm; for the experimental tips, the range was 0.18–1.58 nm. Over the tested range of roughness, the measured work of adhesion was found to decrease by more than an order of magnitude as the roughness increased. The dependence of adhesion upon roughness was accurately described using a simple analytical model. This combination of simulation and experimental methodologies allows for an exploration of an unprecedented range of tip sizes and length scales for roughness, while also verifying consistency of the results between the techniques. Collectively, these results demonstrate the high sensitivity of adhesion to interfacial roughness down to the atomic limit. Furthermore, they indicate that care must be taken when attempting to extract work of adhesion values from experimental measurements of adhesion forces.

Summary. Previous clinical studies have demonstrated an association between the hepatitis B e antigen and Toll-like receptor (TLR) expression and signalling. Therefore, the aim of this study was to develop an in vitro assay to measure the effect of hepatitis B virus proteins, including the precore protein, on signalling mediated by members of the Toll-like/interleukin 1 (TIR) superfamily, by measuring NF-κB promoter activity. The basal level of NF-κB reporter activity was measured in three hepatocyte cell lines (Huh7, HepG2 and PH5CH8) and one kidney cell line (HEK293) using a luciferase assay. All cell lines were virtually refractory to stimulation with lipopolysaccharide; however, PH5CH8 cells had a robust activation of NF-κB in response to IL-1β stimulation, with ∼40-fold higher activation than the unstimulated control, a higher degree of activation than that observed in either Huh7 and HepG2, or HEK293 and HEK293-TLR2 cells. In PH5CH8 cells transfected with pCI expression constructs and stimulated with IL-1β, we showed that the precursor form of the precore protein, p25, inhibits NF-κB activation by up to 30% and the cytosolic form, p22, inhibits NF-κB activation by 70%. The core protein, p21, which shares significant homology with the precore protein except for a 10-amino acid extension at the N-terminus, had no effect on NF-κB activation. We hypothesize that the inhibition of IL-1β-mediated NF-κB activation by the precore protein may be a mechanism that allows the virus to persist, suggesting a role for the pool of precore protein that remains intracellular.

Short time molecular dynamics simulations were performed to model C60 and Au3 bombardment of an amorphous water sample in the projectile energy range of 5–120 keV. A previously proposed friction model has been applied to describe the fundamental motion of a projectile during cluster bombardment of a solid. This simple analytical model uses a definition of friction on a single particle to describe the cluster movement through a medium. Although the mathematics of the friction model vary among systems, the projectile motion and energy deposition of a single particle into the sample as well as the reactive environment created is close to that of C60 bombardment.

A series of computational investigations has been performed to examine the mesoscale energy dynamics of cluster bombardment events on a variety of systems. Through the development and application of the mesoscale energy deposition footprint (MEDF) model, we have successfully predicted the yield trends exhibited by a variety of projectiles and incident energies. The details of this model, dynamics of the damaged region, and comparison to experimental SIMS results are presented. The general cluster behavior which is revealed by this study is also discussed.

The nature of the regions that are favorable for chemical reactions has been investigated for a pure amorphous water ice substrate following energetic bombardment by C60 and Au3 cluster projectiles using molecular dynamics (MD) simulations. The simulations show that both projectiles, especially C60, produce regions where a plethora of reactions occur at elevated densities indicating that multiple atoms or molecules are involved simultaneously in the reactions initiated by cluster bombardment. The total number of reacted water molecules is significantly less than the total sputtering yield, which confirms that both cluster projectiles are useful for molecular depth profiling experiments.

In this study, we explore the wear behavior of amplitude modulation atomic force microscopy (AM-AFM, an intermittent-contact AFM mode) tips coated with a common type of diamond-like carbon, amorphous hydrogenated carbon (a-C:H), when scanned against an ultra-nanocrystalline diamond (UNCD) sample both experimentally and through molecular dynamics (MD) simulations. Finite element analysis is utilized in a unique way to create a representative geometry of the tip to be simulated in MD. To conduct consistent and quantitative experiments, we apply a protocol that involves determining the tip-sample interaction geometry, calculating the tip-sample force and normal contact stress over the course of the wear test, and precisely quantifying the wear volume using high-resolution transmission electron microscopy imaging. The results reveal gradual wear of a-C:H with no sign of fracture or plastic deformation. The wear rate of a-C:H is consistent with a reaction-rate-based wear theory, which predicts an exponential dependence of the rate of atom removal on the average normal contact stress. From this, kinetic parameters governing the wear process are estimated. MD simulations of an a-C:H tip, whose radius is comparable to the tip radii used in experiments, making contact with a UNCD sample multiple times exhibit an atomic-level removal process. The atomistic wear events observed in the simulations are correlated with under-coordinated atomic species at the contacting surfaces.

Molecular dynamics (MD) simulations have been shown to be an effective tool for gaining insight into the physical phenomena that occur during cluster bombardment. Numerous simulations have illuminated aspects of the crater formation and subsequent ejection of material. At this stage, simulations are generally performed by aiming the projectile normal to the surface in order to simplify the subsequent analysis of ejected particles while experiments are performed at an off-normal angle of incidence. The importance of incident angle is well established for atomic bombardment, but the effect for cluster bombardment is not completely established. There have been a few studies that have discussed the influence of incident angle on sputter yield. Hill and Blenkinsopp observed an increase of Si yield when Si is bombarded with 15 keV C +

Molecular dynamics simulations of energetic cluster bombardment (C 20 , C 60 , C 120 , C 180 ) are performed in the range of 5-20 keV on a solid benzene substrate. The goal is to study the trends exhibited by these bombardment events and to develop a simple analytical model that explains the general dynamics associated with cluster projectiles. These results indicate that the dynamics of these clusters can be described by a macroscale quadratic friction model and thus can provide an interpretation for the dependencies on cluster mass and size, as well as the observation that velocity of the cluster relative to its initial value decays exponentially with time with a decay constant that linearly depends on the initial velocity.