A classical view on nonclassical nucleation

Understanding and controlling nucleation is important for many crystallization applications. Calcium carbonate (CaCO_{3}) is often used as a model system to investigate nucleation mechanisms. Despite its great importance in geology, biology, and many industrial applications, CaCO_{3} nucleation is still a topic of intense discussion, with new pathways for its growth from ions in solution proposed in recent years. These new pathways include the so-called nonclassical nucleation mechanism via the assembly of thermodynamically stable prenucleation clusters, as well as the formation of a dense liquid precursor phase via liquid–liquid phase separation. Here, we present results from a combined experimental and computational investigation on the precipitation of CaCO_{3} in dilute aqueous solutions. We propose that a dense liquid phase (containing 4–7 H_{2}O per CaCO_{3} unit) forms in supersaturated solutions through the association of ions and ion pairs without significant participation of larger ion clusters. This liquid acts as the precursor for the formation of solid CaCO_{3} in the form of vaterite, which grows via a net transfer of ions from solution according to z Ca^{2+} + zCO_{3}^{2−} → z CaCO_{3}. The results show that all steps in this process can be explained according to classical concepts of crystal nucleation and growth, and that long-standing physical concepts of nucleation can describe multistep, multiphase growth mechanisms

Opposing associations of depression with sexual behaviour: implications for epidemiological investigation among gay, bisexual and other men who have sex with men

OBJECTIVE: The aim of this report is to investigate the nature of the relationship between depression and condomless sex (CLS) among gay, bisexual and other men who have sex with men (GBMSM). METHODS: Data are from the Antiretrovirals, Sexual Transmission Risk and Attitude (ASTRA) study of people living with HIV and attending one of eight HIV outpatient clinics in England (2011-2012) and the Attitudes to and Understanding of Risk of Acquisition of HIV (AURAH) study of HIV-negative/unknown status individuals attending one of 20 genitourinary medicine clinics in England (2013-2014). This analysis included GBMSM only. For each study, the prevalence of depressive symptoms (Patient Health Questionnaire-9 score ≥10) was presented according to three categories of sex in the past 3 months (considering anal/vaginal sex with men/women and anal sex with men in separate definitions): (1) no sex, (2) condom-protected sex only and (3) CLS. Multinomial logistic regression with 'condom-protected sex only' as the reference group was used to adjust for age and (for ASTRA participants) time since HIV diagnosis. RESULTS: There were opposing associations of depression with recent sexual behaviour: the prevalence of depression was higher among those who reported no sex and those who reported CLS, compared with those who reported condom-protected sex only. Among the 2170 HIV-positive GBMSM in ASTRA, considering anal/vaginal sex with men/women, the prevalence of depressive symptoms was 32%, 20% and 28%, respectively, among men reporting no sex (n=783), condom-protected sex only (n=551) and CLS (n=836) (global p<0.001). Among the 1477 HIV-negative GBMSM in AURAH, the prevalence of depressive symptoms was 12%, 8% and 13%, respectively, for no sex (n=137), condom-protected sex only (n=487) and CLS (n=853) (global p=0.017). Patterns were similar after adjustment and when only considering anal sex between men. CONCLUSIONS: Depression may be linked both to lack of sexual activity and to sexual risk taking. When investigating associations between depression and CLS, it is important to separate out individuals reporting condom-protected sex only from those reporting no sex

Clinically significant depressive symptoms and sexual behaviour among men who have sex with men.

BACKGROUND: The relationship between depression and sexual behaviour among men who have sex with men (MSM) is poorly understood. AIMS: To investigate prevalence and correlates of depressive symptoms (Patient Health Questionnaire-9 score ≥10) and the relationship between depressive symptoms and sexual behaviour among MSM reporting recent sex. METHOD: The Attitudes to and Understanding of Risk of Acquisition of HIV (AURAH) is a cross-sectional study of UK genitourinary medicine clinic attendees without diagnosed HIV (2013-2014). RESULTS: Among 1340 MSM, depressive symptoms (12.4%) were strongly associated with socioeconomic disadvantage and lower supportive network. Adjusted for key sociodemographic factors, depressive symptoms were associated with measures of condomless sex partners in the past 3 months (≥2 (prevalence ratio (PR) 1.42, 95% CI 1.17-1.74; P=0.001), unknown or HIV-positive status (PR 1.43, 95% CI 1.20-1.71; P<0.001)), sexually transmitted infection (STI) diagnosis (PR 1.46, 95% CI 1.19-1.79; P<0.001) and post-exposure prophylaxis use in the past year (PR 1.83, 95% CI 1.33-2.50; P<0.001). CONCLUSIONS: Management of mental health may play a role in HIV and STI prevention. DECLARATION OF INTEREST: A.N.P. has received payments for presentations made at meetings sponsored by Gilead in spring 2015. N.C.N. has received support for attendance at conferences, speaker fees and payments for attendance at advisory boards from Gilead Sciences, Viiv Healthcare, Janssen Pharmaceuticals and Bristol-Myers Squibb and a research grant from Gilead Sciences. D.A. served on the advisory board for Gilead in January 2016. M.M.G. has had sponsorship to attend conferences by Bristol-Myers Squibb, been on the BioCryst advisory board and run trials for Merck, Gilead, SSAT, BioCryst and Novartis. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license

Trends in HIV incidence between 2013-2019 and association of baseline factors with subsequent incident HIV among gay, bisexual, and other men who have sex with men attending sexual health clinics in England: A prospective cohort study.

BACKGROUND: Prospective cohort studies of incident HIV and associated factors among gay, bisexual, and other men who have sex with men (GBMSM) in the United Kingdom are lacking. We report time trends in and factors associated with HIV incidence between 2013 and 2019 among a cohort of GBMSM: the AURAH2 prospective study. METHODS AND FINDINGS: Participants were recruited through 1 of 3 sexual health clinics in London and Brighton (July 2013 to April 2016) and self-completed a baseline paper questionnaire and subsequent 4-monthly and annual online questionnaires (March 2015 to March 2018), including information on sociodemographics, lifestyle, health and well-being, HIV status, sexual/HIV-related behaviours, and preexposure prophylaxis and postexposure prophylaxis (PrEP/PEP). Incident HIV was ascertained by linkage with national HIV surveillance data from Public Health England (PHE). We investigated the associations of HIV incidence with (1) baseline factors using mixed-effects Weibull proportional hazard models, unadjusted and adjusted for age, country of birth and ethnicity, sexuality, and education level; and (2) time-updated factors, using mixed-effects Poisson regression models. In total, 1,162 men (mean age 34 years, 82% white, 94% gay, 74% university-educated) were enrolled in the study. Thirty-three HIV seroconversions occurred over 4,618.9 person-years (PY) of follow-up: an overall HIV incidence rate (IR) of 0.71 (95% confidence interval (CI) 0.51 to 1.00) per 100 PY. Incidence declined from 1.47 (95% CI 0.48 to 4.57) per 100 PY in 2013/2014 to 0.25 (95% CI 0.08 to 0.78) per 100 PY in 2018/2019; average annual decline was 0.85-fold (p 10 partners [7/57]; 5 to 10 partners [5/60]; and 2 to 4 partners [11/293]: 14.04, 95% CI 4.11 to 47.98; 9.60, 95% CI 2.58 to 35.76; and 4.05, 95% CI 1.29 to 12.72, respectively, p 100 new partners: 3.17, 95% CI 1.39 to 7.26; 4.40, 95% CI 1.35 to 14.29; and 4.84, 95% CI 1.05 to 22.4, respectively, p < 0.001). Results were broadly consistent for time-updated analysis (n = 622 men). The study's main limitation is that men may not be representative of the broader GBMSM population in England. CONCLUSIONS: We observed a substantial decline in HIV incidence from 2013 to 2019 among GBMSM attending sexual health clinics. Injection drug use, chemsex use, and measures of high-risk sexual behaviour were strongly associated with incident HIV. Progress towards zero new infections could be achieved if combination HIV prevention including Test and Treat strategies and routine commissioning of a PrEP programme continues across the UK and reaches all at-risk populations

Investigating Conceptual Models for the Relationship Between Depression and Condomless Sex Among Gay, Bisexual, and Other Men Who have Sex with Men: Using Structural Equation Modelling to Assess Mediation

The aim of this study is to investigate five hypothesized mechanisms of causation between depression and condomless sex with ≥ 2 partners (CLS2+) among gay, bisexual, and other men who have sex with men (GBMSM), involving alternative roles of self-efficacy for sexual safety and recreational drug use. Data were from the AURAH cross-sectional study of 1340 GBMSM attending genitourinary medicine clinics in England (2013–2014). Structural equation modelling (SEM) was used to investigate which conceptual model was more consistent with the data. Twelve percent of men reported depression (PHQ-9 ≥ 10) and 32% reported CLS2+ in the past 3 months. AURAH data were more consistent with the model in which depression was considered to lead to CLS2+ indirectly via low self-efficacy for sexual safety (indirect Beta = 0.158; p < 0.001) as well as indirectly via higher levels of recreational drug use (indirect Beta = 0.158; p < 0.001). SEM assists in understanding the relationship between depression and CLS among GBMSM

Recreational drug use and use of drugs associated with chemsex among HIV-negative and HIV-positive heterosexual men and women attending sexual health and HIV clinics in England

Background: There is little information on the prevalence of recreational drug use among UK heterosexual men and women, in particular on use of drugs associated with ‘chemsex’ within gay communities. The aim of this study was to examine among HIV-negative and HIV-positive heterosexual men and women in England: (i) the prevalence of recreational drug use (including use of drugs associated with chemsex), (ii) socio-economic/lifestyle correlates of drug use, and (iii) the association of drug use with sexual behavior measures and mental health symptoms. Methods: Data are from the AURAH study of HIV-negative individuals attending sexual health clinics across England (2013–2014) and the ASTRA study of HIV-positive individuals attending HIV outpatient clinics in England (2011–2012). Prevalence of recreational drug use (past three months) and associations are presented separately among the four sample groups: HIV-negative (N = 470) and HIV-positive (N = 373) heterosexual men and HIVnegative (N = 676) and HIV-positive (N = 637) women. Results: The age standardized prevalence of any drug use was 22.9%, 17.1%, 15.3%, and 7.1% in the four sample groups respectively. In all groups, cannabis was the drug most commonly used (range from 4.7% to 17.9%) followed by cocaine (1.6% to 8.5%). The prevalence of use of drugs associated with chemsex was very low among HIV-negative participants (1.0% heterosexual men, 0.2% women) and zero among HIV-positive men and women. In age-adjusted analysis, factors linked to drug use overall and/or to cannabis and cocaine use specifically in the four sample groups included Black/mixed Caribbean and white (vs. Black/mixed African) ethnicity, lower level of education , cigarette smoking, and higher risk alcohol consumption. Associations of recreational drug use with measures of condomless sex, depression, and anxiety were observed in the four groups, but were particularly strong/apparent among women. Conclusion: Providers need to be aware of cannabis and cocaine use and its potential link with sexual risk behavior and symptoms of depression and anxiety among heterosexual men and women attending sexual health and HIV clinics

Ethnicity and sexual risk in heterosexual people attending sexual health clinics in England: a cross-sectional, self-administered questionnaire study.

OBJECTIVES: In the UK, people of black ethnicity experience a disproportionate burden of HIV and STI. We aimed to assess the association of ethnicity with sexual behaviour and sexual health among women and heterosexual men attending genitourinary medicine (GUM) clinics in England. METHODS: The Attitudes to and Understanding of Risk of Acquisition of HIV is a cross-sectional, self-administered questionnaire study of HIV negative people recruited from 20 GUM clinics in England, 2013-2014. Modified Poisson regression with robust SEs was used to calculate adjusted prevalence ratios (aPR) for the association between ethnicity and various sexual risk behaviours, adjusted for age, study region, education and relationship status. RESULTS: Questionnaires were completed by 1146 individuals, 676 women and 470 heterosexual men. Ethnicity was recorded for 1131 (98.8%) participants: 550 (48.6%) black/mixed African, 168 (14.9%) black/mixed Caribbean, 308 (27.2%) white ethnic groups, 105 (9.3%) other ethnicity. Compared with women from white ethnic groups, black/mixed African women were less likely to report condomless sex with a non-regular partner (aPR (95% CI) 0.67 (0.51 to 0.88)), black/mixed African and black/mixed Caribbean women were less likely to report two or more new partners (0.42 (0.32 to 0.55) and 0.44 (0.29 to 0.65), respectively), and black/mixed Caribbean women were more likely to report an STI diagnosis (1.56 (1.00 to 2.42)). Compared with men from white ethnic groups, black/mixed Caribbean men were more likely to report an STI diagnosis (1.91 (1.20 to 3.04)), but did not report risk behaviours more frequently. Men and women of black/mixed Caribbean ethnicity remained more likely to report STI history after adjustment for sexual risk behaviours. DISCUSSION: Risk behaviours were reported less frequently by women of black ethnicity; however, history of STI was more prevalent among black/mixed Caribbean women. In black/mixed Caribbean men, higher STI history was not explained by ethnic variation in reported risk behaviours. The association between STI and black/mixed Caribbean ethnicity remained after adjustment for risk behaviours

Risk, reassurance and routine: a qualitative study of narrative understandings of the potential for HIV self-testing among men who have sex with men in England

BACKGROUND: HIV testing has seen a rapid evolution over the last decade with multiple modalities now in use globally. In recent years HIV self-testing (HIVST) has been legalised in the UK paving the way for further expansion of testing. Interventions are delivered in particular social contexts which shape uptake. It is therefore important to understand how novel interventions are likely to be received by their intended users. This study aims to understand how HIVST compliments existing testing strategies considered or adopted by men who have sex with men (MSM). We do this by analysing normative discourses surrounding HIV testing and their perceptions of HIVST's potential future roles. METHODS: Six focus group discussions (FGDs) were conducted with 47 MSM in London, Manchester and Plymouth. One focus group included only MSM who reported higher risk behaviours and one with those who had never tested for HIV. Data were analysed through a thematic framework analysis. RESULTS: Three main narratives for testing for HIV were identified: (i) testing in response to a specific risk event; (ii) as reassurance when there was a small amount of doubt or anxiety related to HIV; and (iii) in response to social norms perpetuated through peers, HIV community groups and the medical establishment to test regularly for HIV. HIVST had limited utility for men when testing in response to specific risk events except in the case of significant structural barriers to other testing opportunities. HIVST was considered to have utility when seeking reassurance, and was thought to be very useful when testing to satisfy the needs and expectations of others around regular testing. There was some ambivalence about the incursion of a clinical intervention into the home. CONCLUSIONS: HIVST following risk events will likely be limited to those for whom existing service provision is insufficient to meet immediate needs based on structural or personal barriers to testing. Obligations of biological citizenship are central to MSM's understanding of the utility of HIVST. In the context of discourses of biocitizenship, men perceive HIVST to have dual roles: firstly as a tool to manage (mild) anxiety around one's HIV status based on an acknowledgment of HIV vulnerability arising from being homosexually active. Secondly, HIVST is useful in complying with social norms and meeting the perceived demands of biomedicine

Comparing multiple competing interventions in the absence of randomized trials using clinical risk-benefit analysis

<p>Abstract</p> <p>Background</p> <p>To demonstrate the use of risk-benefit analysis for comparing multiple competing interventions in the absence of randomized trials, we applied this approach to the evaluation of five anticoagulants to prevent thrombosis in patients undergoing orthopedic surgery.</p> <p>Methods</p> <p>Using a cost-effectiveness approach from a clinical perspective (i.e. risk benefit analysis) we compared thromboprophylaxis with warfarin, low molecular weight heparin, unfractionated heparin, fondaparinux or ximelagatran in patients undergoing major orthopedic surgery, with sub-analyses according to surgery type. Proportions and variances of events defining risk (major bleeding) and benefit (thrombosis averted) were obtained through a meta-analysis and used to define beta distributions. Monte Carlo simulations were conducted and used to calculate incremental risks, benefits, and risk-benefit ratios. Finally, net clinical benefit was calculated for all replications across a range of risk-benefit acceptability thresholds, with a reference range obtained by estimating the case fatality rate - ratio of thrombosis to bleeding.</p> <p>Results</p> <p>The analysis showed that compared to placebo ximelagatran was superior to other options but final results were influenced by type of surgery, since ximelagatran was superior in total knee replacement but not in total hip replacement.</p> <p>Conclusions</p> <p>Using simulation and economic techniques we demonstrate a method that allows comparing multiple competing interventions in the absence of randomized trials with multiple arms by determining the option with the best risk-benefit profile. It can be helpful in clinical decision making since it incorporates risk, benefit, and personal risk acceptance.</p