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We describe the case of a 70-year-old never smoker with chronic lymphocytic leukaemia, treated with single agent ibrutinib therapy. Chest imaging noted nodular change and mediastinal lymphadenopathy, which showed avid uptake on positron emission tomography and guided subsequent biopsies (bronchoscopy using endobronchial ultrasound, mediastinoscopy). Despite negative aspergillus blood immunology tests, he was found to have invasive aspergillosis, which is a known risk with ibrutinib therapy. He has since been successfully treated with antifungal therapy.

Background:\ud \ud Drug use among gay and bisexual men (GBM) is higher than most populations. The use of crystal methamphetamine, erectile dysfunction medication (EDM), and amyl nitrite have been associated with sexual risk behaviour and HIV infection among gay and bisexual men (GBM).\ud \ud Objective:\ud \ud This paper describes an online prospective observational study of licit and illicit drug use among GBM and explores baseline prevalence of drug use in this sample. Capturing these data poses challenges as participants are required to disclose potentially illegal behaviours in a geographically dispersed country. To address this issue, an entirely online and study specific methodology was chosen.\ud \ud Methods:\ud \ud Men living in Australia, aged 16.5 years of age or older, who identified as homosexual or bisexual or had sex with at least one man in the preceding 12 months were eligible to enrol.\ud \ud Results:\ud \ud Between September 2014 and July 2015, a total of 2250 participants completed the baseline questionnaire, of whom, 1710 (76.0%) consented to six-monthly follow-up. The majority (65.7%) were recruited through Facebook targeted advertising. At baseline, over half (50.5%) the men reported the use of any illicit drug in the previous six months, and 28.0% had used party drugs. In the six months prior to enrolment, 12.0% had used crystal methamphetamine, 21.8% had used EDM, and 32.1% had used amyl nitrite. Among the 1710 men enrolled into the cohort, 790 men had used none of these drugs.\ud \ud Conclusion:\ud \ud Ease of entry and minimal research burden on participants helped ensure successful recruitment into this online cohort study. Study outcomes will include the initiation and cessation of drug use, associated risk behaviours, and health consequences, over time. Results will provide insights into the role gay community plays in patterns of drug use among GBM.

Methylation is an underpinning process of life and provides control for biological processes such as DNA synthesis, cell growth, and apoptosis. Methionine adenosyltransferases (MAT) produce the cellular methyl donor, S‐Adenosylmethionine (SAMe). Dysregulation of SAMe level is a relevant event in many diseases, including cancers such as hepatocellular carcinoma and colon cancer. In addition, mutation of Arg264 in MATα1 causes isolated persistent hypermethioninemia, which is characterized by low activity of the enzyme in liver and high level of plasma methionine. In mammals, MATα1/α2 and MATβV1/V2 are the catalytic and the major form of regulatory subunits, respectively. A gating loop comprising residues 113–131 is located beside the active site of catalytic subunits (MATα1/α2) and provides controlled access to the active site. Here, we provide evidence of how the gating loop facilitates the catalysis and define some of the key elements that control the catalytic efficiency. Mutation of several residues of MATα2 including Gln113, Ser114, and Arg264 lead to partial or total loss of enzymatic activity, demonstrating their critical role in catalysis. The enzymatic activity of the mutated enzymes is restored to varying degrees upon complex formation with MATβV1 or MATβV2, endorsing its role as an allosteric regulator of MATα2 in response to the levels of methionine or SAMe. Finally, the protein–protein interacting surface formed in MATα2:MATβ complexes is explored to demonstrate that several quinolone‐based compounds modulate the activity of MATα2 and its mutants, providing a rational for chemical design/intervention responsive to the level of SAMe in the cellular environment. Enzymes Methionine adenosyltransferase (http://www.chem.qmul.ac.uk/iubmb/enzyme/EC2/5/1/6.html). Database Structural data are available in the RCSB PDB database under the PDB ID http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6FBN (Q113A), http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6FBP (S114A: P22121), http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6FBO (S114A: I222), http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6FCB (P115G), http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6FCD (R264A), http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6FAJ (wtMATα2: apo), http://www.rcsb.org/pdb/search/structidSearch.do?structureId=6G6R (wtMATα2: holo), Methionine adenosyltransferases (MATs) produce the cellular methyl donor S‐adenosyl‐methionine (SAMe) required for methylation, an essential modification of different biomolecules. Mammalian MATs comprise catalytic (MATα1/α2) and regulatory (MATβV1/MATβV2) subunits. The quinolone‐based compound SCR0915 presumably targets the MATβV2/MATα2 dimer binding interface (red boxes), thus behaving as an allosteric regulator that activates MATα2 when Met or SAMe are at low concentration but inhibits the enzyme when Met or SAMe concentrations are high.

Purpose To establish patient satisfaction after collagenase clostridium histolyticum (CCH) injection. Methods In a cross-sectional study, 213 patients who had been treated for Dupuytren disease with CCH were reviewed between 37 and 1421 days after injection. Results A total of 73% of the patients were very satisfied or satisfied, and 21% were dissatisfied; 75% would probably or definitely have CCH again, whereas 17% probably or definitely would not. We found that satisfaction and willingness to undergo a second treatment decreased over time and had a negative relationship with recurrence. Dissatisfaction was greater in those with a poor initial outcome but not in those with an initial complication. Of 212 patients, 78 had previously experienced surgery for Dupuytren disease of whom 71% would prefer CCH to surgery and 15% the converse. Satisfaction shows a relationship with function as measured by both Quick DASH and the Southampton Dupuytren Scoring Scheme. Conclusions Patient satisfaction with CCH is generally high but deteriorates over time as the disease recurs. To manage patient expectation, this issue should be made explicit to patients in the consent process. Clinical relevance Overall satisfaction with CCH is high, with initial satisfaction rates especially good. Forewarning of complications and recurrence can help maintain satisfaction levels.

PURPOSE OF REVIEW The immunogenic capacity of donor human leukocyte antigen (HLA) to induce humoral immune responses is not an intrinsic property of the mismatched alloantigen but depends on the HLA phenotype of the recipient. In recent years, advances in molecular sequence technology and information from X-ray crystallography have enabled structural comparison of donor and recipient HLA type providing an opportunity for a more rational approach for determining HLA compatibility. In this article, we review studies investigating the molecular basis of antibody-antigen interactions and present computational approaches to determine the complex physiochemical and structural properties of B-cell epitopes. RECENT FINDINGS The relative immunogenicity of individual HLA mismatches may be predicted from analysis of polymorphic amino acids at continuous and discontinuous HLA sequence positions. The use of alloantigen sequence information alone, however, provides limited insight into key determinants of B-cell epitope immunogenicity, such as the orientation, accessibility and physiochemical properties of amino acid side chains. Advances in computational molecular modelling techniques now enable assessment of HLA-alloantibody interactions at the atomic level. Recent evidence supports a strong link between HLA B-cell epitope surface electrostatic potential and their immunogenicity. SUMMARY Assessment of the surface electrostatic properties of HLA alloantigens and computational analyses of HLA-alloantibody interactions represent a promising area for future research into the molecular basis of HLA immunogenicity and antigenicity.

Background Among gay and bisexual men (GBM), ‘serosorting’ is common and involves restricting sex, or at least condomless sex, to partners of the same HIV status. The prevalence of men conveying their serosorting preferences regarding partners they meet online remains unclear. Methods: This study reviewed 57 178 Australian online profiles obtained directly from a popular gay website. Logistic regression was used to identify factors associated with preferences for meeting HIV-positive partners. Results: Men could indicate their preferences from a list of 22 types of partners; 4358 profiles (7.6%) indicated an interest in meeting HIV-positive men. There were 1959 profiles (3.4%) listing a preference for 21 of the 22 types of men, including 1498 men (2.6%) that specifically excluded HIV-positive men. Men who specifically excluded HIV-positive men on their profiles were younger (mean age 34.7 years), less likely to identify as gay (25.6%) and more likely to always prefer ‘safer sex’ (55.3%) than those who specifically included them (mean age 39.6 years; 62.8% gay-identified; 30.9% preferred safer sex; P

Background With increasing use of non-condom-based HIV risk reduction strategies by gay and bisexual men (GBM), we compared occasions of condomless anal intercourse with casual partners (CLAIC) that resulted in HIV transmission and similar occasions when HIV transmission did not occur. Methods We compared two demographically similar samples of Australian GBM. The HIV Seroconversion Study (SCS) was an online cross-sectional survey of GBM recently diagnosed with HIV. The Pleasure and Sexual Health (PASH) study was an online cross sectional survey of GBM generally. Using logistic regression, we compared accounts of CLAIC reported by men in SCS as being the event which led to them acquiring HIV, with recent CLAIC reported by HIV-negative men in PASH. Results In SCS, 85.1% of men reported receptive CLAIC, including 51.8% with ejaculation; 32.1% reported having previously met this partner and 28.6% believed this partner to be HIV-negative. Among HIV-negative men in PASH reporting recent CLAIC, 65.5% reported receptive CLAIC, including 29.9% with ejaculation; 59.3% reported having previously met this partner and 70.1% believed this partner to be HIV-negative. Conclusions While both groups of men engaged in CLAIC, how they engaged in CLAIC differed, and the context in which they did so was different. A generic measure of CLAIC conceals the critical elements of HIV risk, particularly the role of receptive CLAIC, among GBM that distinguish those who seroconverted and those who did not. Detailed information about the context and nature of the practise of CLAIC is required for a more complete understanding of HIV risk among GBM.

Frequent testing of individuals at high risk of HIV is central to current prevention strategies. We aimed to determine if HIV self-testing would increase frequency of testing in high-risk gay and bisexual men, with a particular focus on men who delayed testing or had never been tested before.In this randomised trial, HIV-negative high-risk gay and bisexual men who reported condomless anal intercourse or more than five male sexual partners in the past 3 months were recruited at three clinical and two community-based sites in Australia. Enrolled participants were randomly assigned (1:1) to the intervention (free HIV self-testing plus facility-based testing) or standard care (facility-based testing only). Participants completed a brief online questionnaire every 3 months, which collected the number of self-tests used and the number and location of facility-based tests, and HIV testing was subsequently sourced from clinical records. The primary outcome of number of HIV tests over 12 months was assessed overall and in two strata: recent (last test ≤2 years ago) and non-recent (2 years ago or never tested) testers. A statistician who was masked to group allocation analysed the data; analyses included all participants who completed at least one follow-up questionnaire. After the 12 month follow-up, men in the standard care group were offered free self-testing kits for a year. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12613001236785.Between Dec 1, 2013, and Feb 5, 2015, 182 men were randomly assigned to self-testing, and 180 to standard care. The analysis population included 178 (98%) men in the self-testing group (174 person-years) and 165 (92%) in the standard care group (162 person-years). Overall, men in the self-testing group had 701 HIV tests (410 self-tests; mean 4·0 tests per year), and men in the standard care group had 313 HIV tests (mean 1·9 tests per year); rate ratio (RR) 2·08 (95% CI 1·82-2·38; p0·0001). Among recent testers, men in the self-testing group had 627 tests (356 self-tests; mean 4·2 per year), and men in the standard care group had 297 tests (mean 2·1 per year); RR 1·99 (1·73-2·29; p0·0001). Among non-recent testers, men in the self-testing group had 74 tests (54 self-tests; mean 2·8 per year), and men in the standard care group had 16 tests (mean 0·7 per year); RR 3·95 (2·30-6·78; p0·0001). The mean number of facility-based HIV tests per year was similar in the self-testing and standard care groups (mean 1·7 vs 1·9 per year, respectively; RR 0·86, 0·74-1·01; p=0·074). No serious adverse events were reported during follow-up.HIV self-testing resulted in a two times increase in frequency of testing in gay and bisexual men at high risk of infection, and a nearly four times increase in non-recent testers, compared with standard care, without reducing the frequency of facility-based HIV testing. HIV self-testing should be made more widely available to help increase testing and earlier diagnosis.The National Health and Medical Research Council, Australia.

BACKGROUND Reducing rates of partner change and increasing condom usage among gay men are obvious targets for potentially reducing syphilis transmission among gay men. METHODS We developed an agent-based stochastic model to examine syphilis transmission among a population of gay men, representative of gay men in Australia. This model was used to explore the potential impact of changes in sexual behavior over 1 month, 3 month, and indefinite time frames on syphilis epidemics. RESULTS Simulations of interventions showed that short-term reductions in rates of partner change and increased condom use would have negligible impact on the long-term trends of syphilis epidemics. If no interventions are introduced, then the model forecasts that the syphilis prevalence in the population could continue to rise, with an increase of 80% in the number of men infected with syphilis during the next decade. However, if changes in sexual behavior are maintained in the long-term, then syphilis epidemics can be mitigated. If condom use is sustained at 80% in partnerships that are HIV discordant or of unknown status, then the prevalence of syphilis is estimated to decrease by 9% over 10 years. Similarly, if partner acquisition rates decrease by 25%, then there will be a 22% reduction in syphilis prevalence. CONCLUSIONS Interventions promoting partner reduction or increased condom use would be ineffective in the short-term, and would have limited prospects for success in the long-term unless very large changes in behavior are sustained. Complementary social research indicates that such long-term changes in behavior are unlikely to be adopted, and therefore other intervention strategies need to be developed to reduce syphilis among gay men.

BACKGROUND The community at which public health strategies for reducing syphilis epidemics are potentially targeted may have different considerations with regards to their sexual and health priorities. We aimed to elicit information on the acceptability of behavior change interventions among gay men for reducing syphilis transmission. METHODS We conducted an online survey (n = 2306 participants) and focus groups to determine whether further sexual behavior change to reduce syphilis is likely to be acceptable to gay men in Australia. RESULTS One quarter of survey respondents (26%) indicated that they would be highly likely to reduce partner acquisition rates in order to reduce their chances of syphilis infection. However, among the 475 (21%) men who reported greater than 10 partners in the previous 6 months, only 11% indicated being "highly likely" to reduce partner numbers to avoid syphilis. Among 606 (26%) survey respondents who reported not always using condoms in the previous 6 months, 34% indicated being highly likely to always use condoms with casual partners to avoid syphilis. In the focus groups, men indicated little commitment to sexual behavior change but some willingness to consider short-term changes to reduce community syphilis levels. CONCLUSIONS Interventions promoting partner reduction or increased condom use are unlikely to be adopted on a long-term basis by men at greatest risk. Behavioral interventions alone are unlikely to materially contribute to syphilis prevention among gay men.

Can teachers create teachable moments or do they occur simply by chance? What exactly is meant by “teachable moment”? Discover the value of the teachable moment and how teachers can create those moments to parallel their instruction.

To promote content literacy, students have to be actively involved. This article focuses on strategies that stimulate student interest by involving them with the content during pre-reading, during-reading and post-reading activities. these processes provide students with optimal opportunities for comprehension. The authors recommend the use of a variety of materials to supplement the social studies text, recoginizing, however, that the text, because of its breadth of knowledge will always play an important role. The three instructional activities delineated reinforce the idea that social studies learning is promoted through literacy, just as language acts learning is developed through the social studies. All of the strategies include a form of graphic organizer. They are examples of ways teaches can adapt instruction to promote student interest in social studies. Social studies doesn't have to be boring!

Group sex has consistently been identified as one of a group of risk behaviours among gay men associated with HIV seroconversion. This paper presents a detailed description of how gender, and specifically masculinity, operates as an aspect of the discourse of gay men's group sex. The findings presented in this paper are one part of a multi-aspected discourse analysis through which we are aiming to develop an account of the discourse of gay men's group sex as it was produced in a series of qualitative interviews conducted with gay men who participate in group sex. The interviews were conducted as part of the Three or More Study (TOMS), a larger project that involved a substantial quantitative component. The overarching intent of the discourse analysis is to provide as comprehensive a mapping as possible of this discursive terrain to facilitate the targeted development of HIV and sexual health educational initiatives. The discourse of gay men's group sex reproduces some key formations of masculinity within discourses of gender, which present specific challenges for HIV prevention education. These challenges are outlined at the conclusion of this paper.