Does sexuality matter? A cross-sectional study of drug use, social injecting, and access to injection-specific care among men who inject drugs in Melbourne, Australia.

BACKGROUND: Gay, bisexual and other men who have sex with men (GBMSM) are overrepresented in cohorts of people who inject drugs. GBMSM's substance use is usually explored in the context of its contribution to sexual risk. We examined drug use practices, connectedness to other people who inject drugs, peer-to-peer injecting, and access to care among men who inject drugs in Melbourne, Australia. We aim to describe similarities and differences in these parameters for GBMSM and other men. METHODS: Data were drawn from a prospective cohort study of people who inject drugs conducted in Melbourne, Australia, since 2009. This cross-sectional study used data collected between 2016 and 2021. Descriptive statistics were used to assess differences between GBMSM and other men. RESULTS: Of 525 men who injected drugs over the study period, 48 (9%) identified as gay or bisexual, or reported sex with other men in the past 12 months. GBMSM and other men reported similar socio-demographics, drug practices (age of injecting initiation, most injected drug, peer-to-peer injecting, receptive syringe sharing) and access to injecting-specific care (drug treatment, source of needle-syringes). A significantly greater percentage of GBMSM reported past 12-month hepatitis C testing (69% vs. 52%, p = 0.028) and preferring methamphetamine (31% vs. 16%, p = 0.022). A higher percentage of GBMSM reported knowing > 50 other people who inject drugs (46% vs. 37%), but this difference was not statistically significant. Both groups primarily obtained injecting equipment from needle-syringe programs; a minority had accessed injecting-specific primary care. CONCLUSION: Men who injected drugs in this cohort and those who identified as GBMSM reported similar drug and health-seeking practices. The higher prevalence of methamphetamine injecting among GBMSM may warrant different harm reduction support for this group. Health promotion should utilise opportunities to connect men who inject drugs in Melbourne to injecting-specific primary health care.

Constructing a 'target population': A critical analysis of public health discourse on substance use among gay and bisexual men, 2000-2020.

BACKGROUND: Gay and bisexual men (GBM) have higher substance use prevalences than general population samples - often attributed to stigmatisation of sexual minority identities. We examined how influential public health research on substance use among GBM interprets this behaviour and what GBM-specific identities emerge through the discourses employed. METHODS: We searched Web of Science for publications on substance use among GBM, selecting 60 of the most cited papers published during 2000-2020. We studied the language used to describe and interpret drug-using behaviour using critical discourse analysis, focusing on interpretive repertoires and subject positions. RESULTS: Three distinct discursive tendencies were identified. First, in constructing a target population, GBM who use illicit drugs are positioned as deficient, socially irresponsible, and maladapted to dealing with stigmatisation and HIV risks. Second, in shifting the focus beyond the individual, the gay community is conceptualised as offering a safe space for socialisation. Nonetheless, gay community spaces are problematised as promoting substance use among vulnerable GBM through aggravating loneliness and normalising drug use as a form of maladaptive (avoidance) coping. Third, counterdiscursive movements add nuance, context, and comparisons that relativise rather than generalise substance use and focus on pleasure and self-determination. Such discourses centre the need for interventions that disrupt homophobic socio-structures instead of individualising approaches to limit non-conformity. CONCLUSION: 'Expert' assessments of substance use among GBM perpetuate pathologising understandings of this behaviour and promote abject subject positions, contributing to perpetuations of intergroup stigma and social exclusion based on drug and sexual practices. Our findings highlight the need for deliberate and critical engagement with prior research and a conscious effort to disrupt dominant discourses on GBM's substance use.

Can modifications to how medical imaging findings are reported improve quality of care? A systematic review.

AIM: To synthesise the available evidence about the effects of modifications to diagnostic imaging reports that aim to optimise patient care. MATERIALS AND METHODS: Cochrane methods were used and CENTRAL, MEDLINE, EMBASE, and clinical trials registers were searched from inception to 31 March 2021. Randomised controlled trials of modifications to imaging reports aimed at optimising patient care for any condition were included. Two authors selected studies independently for inclusion, extracted data, assessed risk of bias, and judged certainty of evidence using GRADE. The primary outcome was quality of care (e.g., increased guideline-adherent care, reduced/increased imaging as appropriate). RESULTS: Five trials met eligibility criteria. One tested provision of information about appropriate osteoporosis treatment in bone density reports; two tested provision of criteria and treatment for heart failure in echocardiogram reports; one tested provision of reminders for when routine imaging is not needed in lumbar spine and knee radiography reports; and one tested inclusion of epidemiological data in lumbar spine imaging reports. All trials were susceptible to bias, and four did not blind all participants. Low certainty evidence from two trials found adding information about appropriate care may increase care quality compared to a standard report (RR 1.20 (95% CI 0.96 to 1.50), two trials, 1,548 participants, I2 = 49). This was supported by outcomes of two additional trials that also provided specific clinical guidance. CONCLUSIONS: The present review suggests that providing specific guidance on appropriate clinical intervention in imaging reports may improve patient care. Further high-quality trials are needed to confirm these findings. Prospective PROSPERO registration CRD42020153961.

COVID-19 Vaccine Uptake and Its Impacts in a Cohort of Gay and Bisexual Men in Australia.

Successful use of biomedical forms of HIV risk-reduction may have predisposed many gay and bisexual men (GBM) to vaccination against COVID-19, which may, in turn, affect their sexual behavior. A total of 622 Australian GBM provided weekly data on COVID-19 vaccination history and sexual behaviour between 17 January 2021 and 22 June 2021. We identify factors associated with COVID-19 vaccination, and compare sexual behavior before and since vaccination. Mean age was 47.3 years (SD 14.0). At least one-dose vaccination coverage had reached 57.2%, and 61.3% reported that the majority of their friends intended to be vaccinated. Vaccinated men reported a mean of 1.11 (SD 2.10) weekly non-relationship sex partners before vaccination and 1.62 (SD 3.42) partners following vaccination. GBM demonstrated high confidence in COVID-19 vaccines. Their sexual activity increased following vaccination suggesting that greater sexual freedom may be a specific motivation for vaccine uptake among some men.

A scoping review of sexual transmission related HIV research among key populations in Malaysia: Implications for interventions across the HIV care cascade.

The Malaysian government has committed to 'Fast Tracking the HIV Response' to achieve UNAIDS 2030 targets to end AIDS. The epidemic is concentrated among key populations and has shifted from people who inject drugs to HIV infection through sexual transmission among men who have sex with men, sex workers and transgender people. The aim of this scoping review was to examine social and behavioural research published since 2005 that can inform understanding of each stage of the 90:90:90 treatment cascade (as proposed by UNAIDS), including HIV risk behaviours and testing practices that precede entry. We found a concentration of studies related to predictors or correlates of HIV infections (mostly among men who have sex with men) and a shortfall in literature pertaining to sex workers or transgender people. While several studies examined factors associated with HIV testing, only one examined uptake of antiretroviral therapy and two explored issues of treatment adherence. No study examined broader care and support of people living with HIV. To scale-up effective programmes and apprise investment to achieve the ambitious targets set-out in the Malaysian National HIV/AIDS Strategic Plan, a combination of comprehensive strategic information and evidence generated through primary research is critical.

Predictive Utility of Anthropometric Based Cut-offs in Assessing Excess Adiposity among Preschool Children in a Multiethnic Population

ABSTRACT Objective: Screening for childhood obesity is a necessary step in developing appropriate and effective interventions. We evaluated the diagnostic performance of various recommended international anthropometric cut-offs based on body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), triceps skinfold (TSF), and mid-upper arm circumference (MUAC) in predicting excess adiposity (body fat ≥ 25%) in a random sample of Trinidadian preschoolers. Methods: After obtaining written parental consent, weight, height, WC, TSF, and MUAC were measured in 596 children using standard procedures. These were used to calculate BMI for age, WHtR, TSF-for-age z-scores, and MUAC-for-age z-scores. Percentage body fat was measured using a Tanita-531 foot-to-foot bioelectrical impedance analyser (BIA). Sensitivities, specificities and area under the receiver-operating curve analysis and predictive values were then computed in reference to BIA estimates. Results: The prevalence of excess adiposity was 12.2% and 5.1% among males and females, respectively. Sensitivities for the various cut-offs ranged from 20.0% to 75.0% and 57.1% to 96.9% among males and females, respectively. WHO-BMI recommended cut-offs and those based on MUAC z-scores had significantly higher sensitivities in females than in males. TSF z-scores had significantly lower sensitivities compared to those based on BMI and WHtR among males. Similarly, specificities ranged from 81.3% to 99.9% and 79.8% to 99.9% among males and females, respectively. In girls, cut-offs based on TSF z-scores had a higher likelihood ratio than cut-offs from Centers for Disease Control, International Obesity Task Force and WHtR. Diagnostic performance was not associated with ethnicity. Conclusion: Our results suggest that diagnostic performance was associated with gender and the cut-offs used; however, it was not associated with ethnicity.

HIV self-testing intervention experiences and kit usability: results from a qualitative study among men who have sex with men in the SELPHI (Self-Testing Public Health Intervention) randomized controlled trial in England and Wales.

OBJECTIVES: SELPHI (HIV Self-Testing Public Health Intervention) is the largest randomized controlled trial (RCT) of HIV self-testing (HIVST) in a high-income setting to date, and has recruited 10 000 men who have sex with men (cis- and transgender) and transgender women who have sex with men. This qualitative substudy aimed to explore how those utilizing self-tests experience HIVST and the implications for further intervention development and scale-up. This is the first qualitative study in Europe investigating experiences of HIVST among intervention users, and the first globally examining the experience of using blood-based HIVST. METHODS: Thirty-seven cisgender MSM SELPHI participants from across England and Wales were purposively recruited to the substudy, in which semi-structured interviews were used to explore testing history, HIVST experiences and intervention preferences. Interviews were audio-recorded, transcribed and analysed through a framework analysis. RESULTS: Men accessed the intervention because HIVST reduced barriers related to convenience, stigma and privacy concerns. Emotional responses had direct links to acceptability. Supportive intervention components increased engagement with testing and addressed supportive concerns. HIVST facilitated more frequent testing, with the potential to reduce sexually transmitted infection (STI) screening frequency. Substudy participants with an HIV-positive result (n = 2) linked to care promptly and reported very high acceptability. Minor adverse outcomes (n = 2; relationship discord and fainting) did not reduce acceptability. Ease of use difficulties were with the lancet and the test processing stage. CONCLUSIONS: Intervention components shaped acceptability, particularly in relation to overcoming a perceived lack of support. The intervention was broadly acceptable and usable; participants expressed an unexpected degree of enthusiasm for HIVST, including those with HIV-positive results and individuals with minor adverse outcomes.

Prevalence and correlates of recent injecting drug use among gay and bisexual men in Australia: Results from the FLUX study.

BACKGROUND: While illicit drug use is prevalent among gay and bisexual men (GBM) in Australia, little is known about the factors associated with injecting drug use among GBM. METHODS: The Following Lives Undergoing Change (FLUX) study is a national, online prospective observational cohort investigating drug use among Australian GBM. Eligible participants were men living in Australia who were aged 16.5 years or older, identified as gay or bisexual or had sex with at least one man in the last year. We examined baseline data for associations between socio-demographic and behavioural characteristics and recent (last six months) injecting using log-binomial regression. RESULTS: Of 1995 eligible respondents, 206 (10.3%) reported ever injecting drugs and 93 (4.7%) had injected recently, most commonly crystal (91.4%) and speed (9.7%). Among recent injectors, only 16 (17.2%) reported injecting at least weekly; eight (8.6%) reported recent receptive syringe sharing. Self-reported HIV and HCV prevalence was higher among recent injectors than among other participants (HIV: 46.2% vs 5.0%, p < .001; HCV: 16.1% vs. 1.2%, p < .001). Recent injecting was associated with lifetime use of more drug classes (adjusted prevalence ratio (APR) = 1.31, 95% Confidence Interval (95%CI) 1.21-1.41), longer time since initiating party drug use (APR = 1.02, 95%CI 1.01-1.04), greater numbers of sex partners (2-10 sex partners: APR = 3.44, 95%CI 1.45-8.20; >10 sex partners: APR = 3.21, 95%CI 1.30-7.92), group sex (APR = 1.42, 95%CI 1.05-1.91) and condomless anal intercourse with casual partners (APR = 1.81, 95%CI 1.34-2.43) in the last six months. CONCLUSIONS: Observed associations between injecting and sexual risk reflect a strong relationship between these practices among GBM. The intersectionality between injecting drug use and sex partying indicates a need to integrate harm reduction interventions for GBM who inject drugs into sexual health services and targeted sexual health interventions into Needle and Syringe Programs.

Motivations and values associated with combining sex and illicit drugs ('chemsex') among gay men in South London: findings from a qualitative study.

OBJECTIVES: There is considerable public health concern about the combining of sex and illicit drugs (chemsex) among gay men. With a view to inform supportive therapeutic and clinical interventions, we sought to examine the motivations for engaging in chemsex among gay men living in South London. METHODS: Community advertising recruited 30 gay men for qualitative semi-structured interview. Aged between 21 and 53 years, all lived in South London in the boroughs of Lambeth, Southwark and Lewisham and all had combined crystal methamphetamine, mephedrone and/or γ-hydroxybutyric acid/γ-butyrolactone with sex in the past 12 months. Transcripts were subjected to a thematic analysis. RESULTS: We broadly distinguished two groups of reasons for combining sex and drugs, within which we described eight distinct motivations. The first major group of motivations for combining drugs with sex was that drugs provide the means by which men can have the sex they desire by increasing libido, confidence, disinhibition and stamina. The second major group of motivations for chemsex was that drugs enhance the qualities of the sex that men value. Drugs made other men seem more attractive, increased physical sensations, intensified perceptions of intimacy and facilitated a sense of sexual adventure. CONCLUSION: Analysis revealed that sexualised drug use provides both motivation and capability to engage in the kinds of sex that some gay men value: sex that explores and celebrates adventurism. Those services providing (talking) interventions to men engaging in chemsex should consider these benefits of sexualised drug use alongside the harms arising.

Underestimated risks of recurrent long-range ash dispersal from northern Pacific Arc volcanoes.

Widespread ash dispersal poses a significant natural hazard to society, particularly in relation to disruption to aviation. Assessing the extent of the threat of far-travelled ash clouds on flight paths is substantially hindered by an incomplete volcanic history and an underestimation of the potential reach of distant eruptive centres. The risk of extensive ash clouds to aviation is thus poorly quantified. New evidence is presented of explosive Late Pleistocene eruptions in the Pacific Arc, currently undocumented in the proximal geological record, which dispersed ash up to 8000 km from source. Twelve microscopic ash deposits or cryptotephra, invisible to the naked eye, discovered within Greenland ice-cores, and ranging in age between 11.1 and 83.7 ka b2k, are compositionally matched to northern Pacific Arc sources including Japan, Kamchatka, Cascades and Alaska. Only two cryptotephra deposits are correlated to known high-magnitude eruptions (Towada-H, Japan, ca 15 ka BP and Mount St Helens Set M, ca 28 ka BP). For the remaining 10 deposits, there is no evidence of age- and compositionally-equivalent eruptive events in regional volcanic stratigraphies. This highlights the inherent problem of under-reporting eruptions and the dangers of underestimating the long-term risk of widespread ash dispersal for trans-Pacific and trans-Atlantic flight routes.

Evaluation of measurement properties of self-administered PROMs aimed at patients with non-specific shoulder pain and "activity limitations": a systematic review.

OBJECTIVE: To critically appraise and compare the measurement properties of self-administered patient-reported outcome measures (PROMs) focussing on the shoulder, assessing "activity limitations." STUDY DESIGN: Systematic review. The study population had to consist of patients with shoulder pain. We excluded postoperative patients or patients with generic diseases. The methodological quality of the selected studies and the results of the measurement properties were critically appraised and rated using the COSMIN checklist. RESULTS: Out of a total of 3427 unique hits, 31 articles, evaluating 7 different questionnaires, were included. The SPADI is the most frequently evaluated PROM and its measurement properties seem adequate apart from a lack of information regarding its measurement error and content validity. CONCLUSION: For English, Norwegian and Turkish users, we recommend to use the SPADI. Dutch users could use either the SDQ or the SST. In German, we recommend the DASH. In Tamil, Slovene, Spanish and the Danish languages, the evaluated PROMs were not yet of acceptable validity. None of these PROMs showed strong positive evidence for all measurement properties. We propose to develop a new shoulder PROM focused on activity limitations, taking new knowledge and techniques into account.

Illicit drug use in sexual settings ('chemsex') and HIV/STI transmission risk behaviour among gay men in South London: findings from a qualitative study.

BACKGROUND: 'Chemsex' is a colloquial term used in the UK that describes sex under the influence of psychoactive substances (typically crystal methamphetamine, mephedrone and gamma-hydroxybutyric acid (GHB)/gamma-butyrolactone (GBL)). Recently, concern has been raised as to the impact of such behaviour on HIV/sexually transmitted infection (STI) transmission risk behaviour, which this qualitative study aimed to explore via semistructured interviews with gay men living in three South London boroughs. METHODS: Interviews were conducted with 30 community-recruited gay men (age range 21-53) who lived in the boroughs of Lambeth, Southwark and Lewisham, and who had used crystal methamphetamine, mephedrone or GHB/GBL either immediately before or during sex with another man during the previous 12 months. Data were subjected to a thematic analysis. RESULTS: Chemsex typically featured more partners and a longer duration than other forms of sex, and the relationship between drug use and HIV/STI transmission risk behaviour was varied. While some men believed that engaging in chemsex had unwittingly led them to take risks, others maintained strict personal rules about having safer sex. Among many participants with diagnosed HIV, there was little evidence that the use of drugs had significantly influenced their engagement in condomless anal intercourse (primarily with other men believed to be HIV positive), but their use had facilitated sex with more men and for longer. CONCLUSIONS: Analysis revealed that, within this sample, chemsex is never less risky than sex without drugs, and is sometimes more so. Targeted clinic-based and community-based harm reduction and sexual health interventions are required to address the prevention needs of gay men combining psychoactive substances with sex.

Caramiphen edisylate as adjunct to standard therapy attenuates soman-induced seizures and cognitive deficits in rats.

The progression of epileptiform activity following soman (GD) exposure is characterized by a period of excessive cholinergic activity followed by excessive glutamatergic activity resulting in status epilepticus, which may lead to neuropathological damage and behavioral deficits. Caramiphen edisylate is an anticholinergic drug with antiglutamatergic properties, which conceptually may be a beneficial therapeutic approach to the treatment of nerve agent exposure. In the present study, rats were exposed to 1.2 LD50 GD or saline, treated with atropine sulfate (2mg/kg, im) and HI-6 (93.6mg/kg, im) 1min after GD exposure, and monitored for seizure activity. Rats were treated with diazepam (10mg/kg, sc) and caramiphen (0, 20 or 100mg/kg, im) 30min after seizure onset. Following GD exposure, performance was evaluated using a battery of behavioral tests to assess motor coordination and function, sensorimotor gating, and cognitive function. Caramiphen as adjunct to diazepam treatment attenuated GD-induced seizure activity, neuropathological damage, and cognitive deficits compared to diazepam alone, but did not attenuate the GD-induced sensorimotor gating impairment. These findings show that physiological, behavioral, and neuropathological effects of GD exposure can be attenuated by treatment with caramiphen as an adjunct to therapy, even if administration is delayed to 30min after seizure onset.

Olfactory cues increase avoidance behavior and induce Fos expression in the amygdala, hippocampus and prefrontal cortex of socially defeated mice.

Genes and proteins of the Fos family are used as markers of neuronal activity and can be modulated by stress. This study investigated whether social defeat (SD) or exposure to an olfactory cue associated with the SD experience activated Fos and FosB/DeltaFosB (ΔFosB) expression in brain regions implicated in the development of post-traumatic stress disorder. Mice exposed to acute SD showed more Fos positive cells in the basolateral amygdala (BLA), CA1 of the hippocampus and the medial prefrontal cortex (mPFC) 1h after SD, and had greater expression of the more persistent FosB/ΔFosB protein in the BLA 24 h after SD compared to controls. Mice exposed to an olfactory cue 24 h or 7 days after SD had higher levels of Fos expression in all three regions 1h after exposure to the cue, and displayed increased avoidance behavior compared to controls. While the avoidance response dissipated with time (less at 7 day vs 24 h after social defeat), Fos expression in the mPFC and CA1 in response to an olfactory cue was greater at 7 days relative to 24 h after social defeat. The results suggest additional processing of the cue-stress association and may provide further support for a role of the mPFC in fear inhibition. These findings may have implications for brain regions and circuitry involved in the avoidance of cues associated with a stressful event that may lead to context-dependent adaptive or maladaptive behavior.

Perceptions of superinfection risk among gay men with diagnosed HIV who have unprotected anal intercourse.

This paper explores how men who have sex with men (MSM) with diagnosed HIV who engage in unprotected anal intercourse (UAI) perceive the potential risk of superinfection and how they respond to it. Semistructured interviews were carried out with 42 MSM recruited via community-based agencies throughout England and Wales. The interviews examined sexual risk taking and the ways in which men sought to manage the risks they perceived. All participants had heard of superinfection and one-third considered it a personal risk when they had UAI with men with the same sero-status. The risk of being superinfected with HIV was often situated among a number of other concerns that men felt they needed to manage when having sex. There was significant uncertainty about the likelihood of acquiring an additional strain of HIV, which was exacerbated by competing, and often conflicting, advice from a variety of expert sources. Men frequently drew upon lay and expert understandings of viral load and infectiousness to rationalize engagement in UAI with other diagnosed positive men. HIV health-care providers should seek to find consensus on how to discuss superinfection with MSM, taking account of the array of other physical and social risks associated with sex.

Exact vortex nucleation and cooperative vortex tunneling in dilute Bose-Einstein condensates.

With the imminent advent of mesoscopic rotating Bose-Einstein condensates in the lowest Landau level regime, we explore lowest Landau level vortex nucleation. An exact many-body analysis is presented in a weakly elliptical trap for up to 400 particles. Striking non-mean-field features are exposed at filling factors >>1. For example, near the critical rotation frequency pairs of energy levels approach each other with exponential accuracy. A physical interpretation is provided by requantizing a mean-field theory, where 1/N plays the role of Planck's constant, revealing two vortices cooperatively tunneling between classically degenerate energy minima. The tunnel splitting variation is described in terms of frequency, particle number, and ellipticity.

Anomalous hydrodynamics and normal fluids in rapidly rotating Bose-Einstein condensates.

In rapidly rotating condensed Bose systems we show that there is a regime of anomalous hydrodynamics which coincides with the mean field quantum Hall regime. A consequence is the absence of a normal fluid in any conventional sense. However, even the superfluid hydrodynamics is not described by conventional Bernoulli and continuity equations. We show that there are constraints which connect spatial variations of density and phase and that the vortex positions are not the simplest description of the dynamics. We demonstrate, inter alia, a simple relation between vortices and surface waves. We show that the surface waves can emulate a "normal fluid," allowing dissipation by energy and angular momentum absorbtion from vortex motion in the trap. The time scale is sensitive to the initial configuration, which can lead to long-lived vortex patches--perhaps related to those observed at JILA.

The effect of desiccation and low temperature on the viability of eggs and emerging larvae of the tick, Rhipicephalus (Boophilus) microplus (Canestrini) (Ixodidae).

Process-based population models need sound and comprehensive data on an animal's response to climatic factors if they are to function reliably under a wide range of climatic conditions. To this end, different aged egg masses of the livestock tick, Rhipicephalus (Boophilus) microplus, were either desiccated in atmospheres with saturation deficits of 5, 10, 15 or 20 mmHg at 20 or 26 degrees C, or chilled at temperatures of 5, 10 or 14 degrees C with a saturation deficit of 1 mmHg for varying periods. The survival rate of the eggs through to hatching was related to the initial age of the eggs, the severity of the treatments and the duration of exposure. We established a relationship between desiccation and weight loss of eggs and, secondarily between weight loss and mortality. Mortality increased with weight loss until it reached 100% when the weight loss was about 35%. Low temperatures were increasingly detrimental to eggs as they reduced from 14 to 5 degrees C. Freshly laid eggs were more susceptible to both low temperatures and desiccation than were older eggs. Larvae emerging from eggs that were stressed by either cold or desiccation lived for a shorter time under optimal conditions than did larvae from eggs incubated under optimal conditions. Larvae from eggs with the same hatching rate had the same viability, whether the stress was induced by desiccation or low temperatures. Models were developed to describe the dynamics of weight loss of eggs with desiccation, the accumulation of cold stress of the eggs, and their effects on egg survival and larval viability. These data provide a sound basis for the development of predictive models for use under field conditions, although the response of different aged eggs to low temperatures was too variable to allow us to develop an accurate model to describe that relationship. Field models will also need to take diurnal temperature fluctuations into account.