Population-centered medical method: A population-centered medical model for public health medicine.

OBJECTIVES: Public health physicians (PHPs) are trained in both medicine and public health, yet practice models in each of these fields incompletely describe their work. A model of practice for public health physicians would better enable training and professional development in the specialty. The objective of this study was to develop an empirically grounded method of the practice of public health medicine by public health physicians. STUDY DESIGN: This was designed as a constructivist grounded theory (CGT) study. Semistructured interviews with 18 public health physicians in Canada were conducted over the course of 1 year. METHODS: Transcribed interviews were coded in three stages (line-by-line, focused, and theoretical). Constant comparison, theoretical sampling, reflective and analytic memos, and team discussion on reflexivity were used to ensure rigor and the proper application of CGT methods. RESULTS: The key finding of this study is the population-centered medical method (POP-CMM), an empirically grounded method of PHP practice. In this model, PHPs bring values, knowledge, and stances to their practice of medicine with populations as patients. They work to diagnose and intervene on public health issues, with a focus on prevention and systems. Essential to this work is knowledge sharing and relationship building between physicians and populations. CONCLUSIONS: POP-CMM represents a method of practice for PHPs. Further exploration of this method in other countries and systems would bring insight into PHP practice globally. The model has important connections to the practice of medicine and presents the possibility of developing a general model of physician practice for a range of patients, from individuals to populations.

Age differences in the behavioural economics of cannabis use: Do adolescents and adults differ on demand for cannabis and discounting of future reward?

BACKGROUND: Adolescence is a period of psychological and neural development in which harms associated with cannabis use may be heightened. We hypothesised that adolescent who use cannabis (adolescentsWUC) would have steeper delay discounting (preference for immediate over future rewards) and greater demand (relative valuation) for cannabis than adults who use cannabis (adultsWUC). METHODS: This cross-sectional study, part of the 'CannTeen' project, compared adultsWUC (n = 71, 26-29 years old) and adolescentsWUC (n = 76, 16-17 years old), and gender- and age-matched adolescent (n = 63) and adult (n = 64) controls. AdolescentsWUC and adultsWUC used cannabis 1-7 days/week and were matched on cannabis use frequency (4 days/week). The Monetary Choice Questionnaire assessed delay discounting. A modified Marijuana Purchase Task (MPT) assessed cannabis demand in adolescentsWUC and adultsWUC. The MPT yielded five indices: intensity (amount of cannabis used at zero cost), Omax (total peak expenditure), Pmax (price at peak expenditure), breakpoint (cost at which cannabis demand is suppressed to zero) and elasticity (degree to which cannabis use decreases with increasing price). Analyses were adjusted for covariates of gender, socioeconomic status, other illicit drug use. RESULTS: Both adolescentsWUC and adultsWUC had steeper delay discounting than controls (F, (1,254)= 9.13, p = 0.003, ηp2= 0.04), with no significant age effect or interaction. AdolescentsWUC showed higher intensity (F, (1,138)= 9.76, p = 0.002, ηp2= 0.07) and lower elasticity (F, (1,138)= 15.25, p < 0.001, ηp2= 0.10) than adultsWUC. There were no significant differences in Pmax, Omax or breakpoint. CONCLUSION: Individuals who use cannabis prefer immediate rewards more than controls. AdolescentsWUC, compared to adultsWUC, may be in a high-risk category with diminished sensitivity to cannabis price increases and a greater consumption of cannabis when it is free.

The CannTeen study: verbal episodic memory, spatial working memory, and response inhibition in adolescent and adult cannabis users and age-matched controls.

BACKGROUND: Preclinical and human studies suggest that adolescent cannabis use may be associated with worse cognitive outcomes than adult cannabis use. We investigated the associations between chronic cannabis use and cognitive function in adolescent and adult cannabis users and controls. We hypothesised user-status would be negatively associated with cognitive function and this relationship would be stronger in adolescents than adults. METHODS: As part of the 'CannTeen' project, this cross-sectional study assessed cognitive performance in adolescent cannabis users (n = 76; 16-17-year-olds), adolescent controls (n = 63), adult cannabis users (n = 71; 26-29-year-olds) and adult controls (n = 64). Users used cannabis 1-7 days/week. Adolescent and adult cannabis users were matched on cannabis use frequency (4 days/week) and time since last use (2.5 days). Verbal episodic memory (VEM) was assessed using the prose recall task, spatial working memory (SWM) was assessed using the spatial n-back task, and response inhibition was assessed with the stop-signal task. Primary outcome variables were: delayed recall, 3-back discriminability, and stop signal reaction time, respectively. RESULTS: Users had worse VEM than controls (F(1,268) = 7.423, p = 0.007). There were no significant differences between user-groups on SWM or response inhibition. Null differences were supported by Bayesian analyses. No significant interactions between age-group and user-group were found for VEM, SWM, or response inhibition. CONCLUSIONS: Consistent with previous research, there was an association between chronic cannabis use and poorer VEM, but chronic cannabis use was not associated with SWM or response inhibition. We did not find evidence for heightened adolescent vulnerability to cannabis-related cognitive impairment.

A comparison of the characteristics, motivations, preferences and expectations of men donating sperm online or through a sperm bank.

STUDY QUESTION: How do the demographic characteristics, motivations, experiences and expectations of unregulated sperm donors (men donating sperm online through a connection website) compare to sperm donors in the regulated sector (men donating through a registered UK sperm bank)? SUMMARY ANSWER: Online donors were more likely to be older, married and have children of their own than sperm bank donors, were more varied in their preferences and expectations of sperm donation, and had more concerns about being a sperm donor. WHAT IS KNOWN ALREADY: While studies have examined motivations and experiences of both regulated sperm bank, and unregulated online sperm donors, no study has directly compared these two groups of donors. STUDY DESIGN, SIZE, DURATION: An email was sent to the 576 men who were registered sperm donors at the London Sperm Bank, the UK's largest sperm bank regulated by the Human Fertilisation and Embryology Authority (HFEA), who had commenced donation between January 2010 and December 2016, and had consented to be contacted for research. The online survey, which contained multiple choice and open-ended questions, was completed by 168 men over a 7-week period. The responses were compared to those of sperm donors registered on Pride Angel, a large UK-based connection website for donors and recipients of sperm: our research team had already collected these data. In total, 5299 sperm donors were on Pride Angel at time of data capture and 400 men had completed a similar survey. The responses of 70 actual online sperm donors (i.e. those whose sperm had been used to conceive at least one child) were used for comparison with the sperm bank donors. PARTICIPANTS/MATERIALS, SETTING, METHODS: The survey obtained data on the sperm donors' demographic characteristics, motivations, experiences and expectations of sperm donation. Data from sperm bank donors were compared to online donors to examine differences between the two groups. The study compared online and clinic donors who had all been accepted as sperm donors: online donors who had been 'vetted' by recipients and sperm bank donors who had passed the rigorous screening criteria set by the clinic. MAIN RESULTS AND THE ROLE OF CHANCE: A response rate of 29% was obtained from the sperm bank donors. Online donors were significantly older than sperm bank donors (mean ± SD: 38.7 ± 8.4 versus 32.9 ± 6.8 years, respectively) and were more likely to have their own children (p < 0.001 for both characteristics). Both groups rated the motivation 'I want to help others' as very important. Online donors rated 'I don't want to have children myself', 'to have children/procreate' and 'to enable others to enjoy parenting as I have myself' as more important than sperm bank donors, whereas sperm bank donors rated financial payment as more important than online donors, as well as confirmation of own fertility. Most (93.9%) online donors had donated their sperm elsewhere, through other connection sites, fertility clinics, sperm banks or friends and family, compared to only 2.4% of sperm bank donors (p < 0.001). There was a significant difference in how donors viewed their relationship to the child, with online donors much less likely than sperm bank donors to see their relationship as a 'genetic relationship only'. Online donors had more concerns about being a donor (p < 0.001), for example, being concerned about 'legal uncertainty and child financial support' and 'future contact and uncertainty about relationship with donor-conceived child'. LIMITATIONS, REASONS FOR CAUTION: Findings may not be representative of all sperm donors as only one online connection site and one HFEA registered sperm bank were used for recruitment. WIDER IMPLICATIONS OF THE FINDINGS: Despite concern regarding shortages of sperm donors in licensed clinics and unease regarding the growing popularity of unregulated connection websites, this is the first study to directly compare online and sperm bank donors. It highlights the importance of considering ways to incorporate unregulated online sperm donors into the regulated sector. With many online donors well aware of the legal risks they undertake when donating in the unregulated online market, this would both increase the number of sperm donors available at clinics but also provide legal protection and support for donors. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Wellcome Trust Grants 104 385/Z/14/Z and 097857/Z/11/Z. The authors have no conflicts of interest.

The effects of cannabidiol on impulsivity and memory during abstinence in cigarette dependent smokers.

Acute nicotine abstinence in cigarette smokers results in deficits in performance on specific cognitive processes, including working memory and impulsivity which are important in relapse. Cannabidiol (CBD), the non-intoxicating cannabinoid found in cannabis, has shown pro-cognitive effects and preliminary evidence has indicated it can reduce the number of cigarettes smoked in dependent smokers. However, the effects of CBD on cognition have never been tested during acute nicotine withdrawal. The present study therefore aimed to investigate if CBD can improve memory and reduce impulsivity during acute tobacco abstinence. Thirty, non-treatment seeking, dependent, cigarette smokers attended two laboratory-based sessions after overnight abstinence, in which they received either 800 mg oral CBD or placebo (PBO), in a randomised order. Abstinence was biologically verified. Participants were assessed on go/no-go, delay discounting, prose recall and N-back (0-back, 1-back, 2-back) tasks. The effects of CBD on delay discounting, prose recall and the N-back (correct responses, maintenance or manipulation) were null, confirmed by a Bayesian analysis, which found evidence for the null hypothesis. Contrary to our predictions, CBD increased commission errors on the go/no-go task. In conclusion, a single 800 mg dose of CBD does not improve verbal or spatial working memory, or impulsivity during tobacco abstinence.

Psilocybin with psychological support improves emotional face recognition in treatment-resistant depression.

RATIONALE: Depressed patients robustly exhibit affective biases in emotional processing which are altered by SSRIs and predict clinical outcome. OBJECTIVES: The objective of this study is to investigate whether psilocybin, recently shown to rapidly improve mood in treatment-resistant depression (TRD), alters patients' emotional processing biases. METHODS: Seventeen patients with treatment-resistant depression completed a dynamic emotional face recognition task at baseline and 1 month later after two doses of psilocybin with psychological support. Sixteen controls completed the emotional recognition task over the same time frame but did not receive psilocybin. RESULTS: We found evidence for a group × time interaction on speed of emotion recognition (p = .035). At baseline, patients were slower at recognising facial emotions compared with controls (p < .001). After psilocybin, this difference was remediated (p = .208). Emotion recognition was faster at follow-up compared with baseline in patients (p = .004, d = .876) but not controls (p = .263, d = .302). In patients, this change was significantly correlated with a reduction in anhedonia over the same time period (r = .640, p = .010). CONCLUSIONS: Psilocybin with psychological support appears to improve processing of emotional faces in treatment-resistant depression, and this correlates with reduced anhedonia. Placebo-controlled studies are warranted to follow up these preliminary findings.

Acute memory and psychotomimetic effects of cannabis and tobacco both 'joint' and individually: a placebo-controlled trial.

BACKGROUND: Cannabis and tobacco have contrasting cognitive effects. Smoking cannabis with tobacco is prevalent in many countries and although this may well influence cognitive and mental health outcomes, the possibility has rarely been investigated in human experimental psychopharmacological research. METHOD: The individual and interactive effects of cannabis and tobacco were evaluated in 24 non-dependent cannabis and tobacco smokers in a randomized, placebo-controlled, double-blind, 2 (cannabis, placebo) × 2 (tobacco, placebo) crossover design. Verbal memory (prose recall), working memory (WM) performance including maintenance, manipulation and attention (N-back), psychotomimetic, subjective and cardiovascular measures were recorded on each of four sessions. RESULTS: Cannabis alone impaired verbal memory. A priori contrasts indicated that tobacco offset the effects of cannabis on delayed recall. However, this was not supported by linear mixed model analysis. Cannabis load-dependently impaired WM. By contrast, tobacco improved WM across all load levels. The acute psychotomimetic effects and ratings of 'stoned' and 'dizzy' induced by cannabis were not altered by tobacco. Cannabis and tobacco had independent effects on increasing heart rate and interacting effects on increasing diastolic blood pressure. CONCLUSIONS: Relative to placebo, acute cannabis impaired verbal memory and WM. Tobacco enhanced performance on WM, independently of cannabis. Moreover, we found some preliminary evidence that tobacco may offset the effects of cannabis on delayed, but not immediate, verbal recall. In contrast, the psychotomimetic and subjective effects of cannabis were unaffected by tobacco co-administration. By reducing the cognitive impairment from cannabis, tobacco co-administration may perpetuate use despite adverse health consequences.

Do Hospital Boards matter for better, safer, patient care?

Manifest failings in healthcare quality and safety in many countries have focused attention on the role of hospital Boards. While a growing literature has drawn attention to the potential impacts of Board composition and Board processes, little work has yet been carried out to examine the influence of Board competencies. In this work, we first validate the structure of an established 'Board competencies' self-assessment instrument in the English NHS (the Board Self-Assessment Questionnaire, or BSAQ). This tool is then used to explore in English acute hospitals the relationships between (a) Board competencies and staff perceptions about how well their organisation deals with quality and safety issues; and (b) Board competencies and a raft of patient safety and quality measures at organisation level. National survey data from 95 hospitals (334 Board members) confirmed the factor structure of the BSAQ, validating it for use in the English NHS. Moreover, better Board competencies were correlated in consistent ways with beneficial staff attitudes to the reporting and handling of quality and safety issues (using routinely collected data from the NHS National Staff Survey). However, relationships between Board competencies and aggregate outcomes for a variety of quality and safety measures showed largely inconsistent and non-significant relationships. Overall, these data suggest that Boards may be able to impact on important staff perceptions. Further work is required to unpack the impact of Board attributes on organisational aggregate outcomes.

Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males.

Preclinical research demonstrates that cannabinoids have differing effects in adolescent and adult animals. Whether these findings translate to humans has not yet been investigated. Here we believe we conducted the first study to compare the acute effects of cannabis in human adolescent (n=20; 16-17 years old) and adult (n=20; 24-28 years old) male cannabis users, in a placebo-controlled, double-blind cross-over design. After inhaling vaporized active or placebo cannabis, participants completed tasks assessing spatial working memory, episodic memory and response inhibition, alongside measures of blood pressure and heart rate, psychotomimetic symptoms and subjective drug effects (for example, 'stoned', 'want to have cannabis'). Results showed that on active cannabis, adolescents felt less stoned and reported fewer psychotomimetic symptoms than adults. Further, adults but not adolescents were more anxious and less alert during the active cannabis session (both pre- and post-drug administration). Following cannabis, cognitive impairment (reaction time on spatial working memory and prose recall following a delay) was greater in adults than adolescents. By contrast, cannabis impaired response inhibition accuracy in adolescents but not in adults. Moreover, following drug administration, the adolescents did not show satiety; instead they wanted more cannabis regardless of whether they had taken active or placebo cannabis, while the opposite was seen for adults. These contrasting profiles of adolescent resilience (blunted subjective, memory, physiological and psychotomimetic effects) and vulnerability (lack of satiety, impaired inhibitory processes) show some degree of translation from preclinical findings, and may contribute to escalated cannabis use by human adolescents.

Salience attribution and its relationship to cannabis-induced psychotic symptoms.

BACKGROUND: Cannabis is a widely used drug associated with increased risk for psychosis. The dopamine hypothesis of psychosis postulates that altered salience processing leads to psychosis. We therefore tested the hypothesis that cannabis users exhibit aberrant salience and explored the relationship between aberrant salience and dopamine synthesis capacity. METHOD: We tested 17 cannabis users and 17 age- and sex-matched non-user controls using the Salience Attribution Test, a probabilistic reward-learning task. Within users, cannabis-induced psychotic symptoms were measured with the Psychotomimetic States Inventory. Dopamine synthesis capacity, indexed as the influx rate constant K i cer , was measured in 10 users and six controls with 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine positron emission tomography. RESULTS: There was no significant difference in aberrant salience between the groups [F 1,32 = 1.12, p = 0.30 (implicit); F 1,32 = 1.09, p = 0.30 (explicit)]. Within users there was a significant positive relationship between cannabis-induced psychotic symptom severity and explicit aberrant salience scores (r = 0.61, p = 0.04) and there was a significant association between cannabis dependency/abuse status and high implicit aberrant salience scores (F 1,15 = 5.8, p = 0.03). Within controls, implicit aberrant salience was inversely correlated with whole striatal dopamine synthesis capacity (r = -0.91, p = 0.01), whereas this relationship was non-significant within users (difference between correlations: Z = -2.05, p = 0.04). CONCLUSIONS: Aberrant salience is positively associated with cannabis-induced psychotic symptom severity, but is not seen in cannabis users overall. This is consistent with the hypothesis that the link between cannabis use and psychosis involves alterations in salience processing. Longitudinal studies are needed to determine whether these cognitive abnormalities are pre-existing or caused by long-term cannabis use.

Online sperm donation: a survey of the demographic characteristics, motivations, preferences and experiences of sperm donors on a connection website.

STUDY QUESTION: What are the demographic characteristics, motivations, preferences and experiences of heterosexual, gay and bisexual sperm donors on a connection website (i.e. a website that facilitates direct contact between donors and recipients of gametes)? SUMMARY ANSWER: This demographically diverse group of men was donating for altruistic reasons and perceived the website as providing greater choice over donation arrangements: approximately one third favoured anonymous donation, most of whom were heterosexual, whilst gay and bisexual donors were more likely to be in contact with children conceived with their sperm. WHAT IS KNOWN ALREADY: Despite substantially more sperm donors being registered on connection websites than with clinics, there has been very little research on this population. Current understanding of the impact of sexual orientation on donors' attitudes is also limited. STUDY DESIGN, SIZE, DURATION: An online survey was conducted over 7 weeks with 383 men registered as sperm donors with Pride Angel, a large UK-based connection website for donors and recipients of sperm. PARTICIPANTS/MATERIALS, SETTING, METHODS: The survey obtained data on participants' demographic characteristics and their motivations, preferences and experiences regarding online sperm donation, including attitudes towards contact with offspring. Differences according to participants' sexual orientation were examined. MAIN RESULTS AND THE ROLE OF CHANCE: Most participants (80.4%, 308) were heterosexual, 10.5% (40) were gay and 9.1% (35) were bisexual; ages ranged from 18 to 69 years (median = 36, mean = 37.3, SD = 9.7). A greater proportion of gay and bisexual men desired open-identity donation (P < 0.005) and contact with offspring (P <0.005) than heterosexual men. Approximately one third (28.7%, 110) had donated sperm; 18.3% (70) had conceived at least one child, of whom a minority (25.7%, 18) were currently in contact with the child, comprising significantly more gay and bisexual than heterosexual men (P = 0.001). Heterosexual men were most likely to state a preference for natural insemination, although the large majority (94.3%, 66) of donors who had conceived children had used artificial insemination. LIMITATIONS, REASONS FOR CAUTION: Findings may not be representative of all sperm donors using connection websites because members of only one website participated and participants were, by necessity, a self-selected sample. WIDER IMPLICATIONS OF THE FINDINGS: This is the first comprehensive study of donors who connect with recipients via the internet, including a substantial number who have donated and conceived children. The findings indicate that sexual orientation may influence men's donation preferences and raise policy issues concerning donor recruitment and the incorporation of online sperm donation into clinical practice. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Wellcome Trust (097857/Z/11/Z). E.T. is the co-founder of Pride Angel; the remaining authors have no conflicts of interest.

Nitrous oxide speeds the reduction of distressing intrusive memories in an experimental model of psychological trauma.

BACKGROUND: Post-traumatic stress disorder (PTSD) involves maladaptive long-term memory formation which underlies involuntary intrusive thoughts about the trauma. Preventing the development of such maladaptive memory is a key aim in preventing the development of PTSD. We examined whether the N-methyl d-aspartate receptor (NMDAR) antagonist gas nitrous oxide (N2O) could reduce the frequency of intrusive memories by inhibiting NMDAR-dependent memory consolidation in a laboratory analogue of psychological trauma. METHOD: Participants were randomized to inhale N2O (N = 25) or medical air (N = 25) after viewing a negatively valenced emotional film clip ('trauma film'). Participants subsequently completed a daily diary assessing frequency of intrusive thoughts relating to the film clip. A week later, participants completed an explicit memory recall task related to the film. RESULTS: Post-encoding N2O sped the reduction in intrusive memory frequency, with a significant reduction by the next day in the N2O group compared to 4 days later in the air group. N2O also interacted with post-film dissociation, producing increased intrusion frequency in those who were highly dissociated at baseline. Sleep length and quality the night after viewing the film did not differ between the groups. CONCLUSION: N2O speeds the reduction of intrusive analogue trauma memory in a time-dependent manner, consistent with sleep-dependent long-term consolidation disruption. Further research with this drug is warranted to determine its potential to inoculate against enduring effects of psychological trauma; however, caution is also urged in dissociated individuals where N2O may aggravate PTSD-like symptomatology.

AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers.

Smoking cannabis daily doubles an individual's risk of developing a psychotic disorder, yet indicators of specific vulnerability have proved largely elusive. Genetic variation is one potential risk modifier. Single-nucleotide polymorphisms in the AKT1 and catechol-O-methyltransferase (COMT) genes have been implicated in the interaction between cannabis, psychosis and cognition, but no studies have examined their impact on an individual's acute response to smoked cannabis. A total 442 healthy young cannabis users were tested while intoxicated with their own cannabis-which was analysed for delta-9-tetrahydrocannbinol (THC) and cannabidiol content-and also ± 7 days apart when drug-free. Psychotomimetic symptoms and working memory were assessed on both the sessions. Variation at the rs2494732 locus of the AKT1 gene predicted acute psychotic response to cannabis along with dependence on the drug and baseline schizotypal symptoms. Working memory following cannabis acutely was worse in females, with some suggestion of an impact of COMT polymorphism on working memory when drug-free. These findings are the first to demonstrate that AKT1 mediates the acute response to cannabis in otherwise healthy individuals and implicate the AKT1 pathway as a possible target for prevention and treatment of cannabis psychosis.

Absence or presence? Complexities in the donor narratives of single mothers using sperm donation.

STUDY QUESTION: How do single mothers who have conceived a child via anonymous or identity-release sperm donation represent the donor? SUMMARY ANSWER: While the majority of mothers described their anonymous and identity-release donors as symbolically significant to their families, others were more likely to emphasize that their lack of information limited their thoughts about him. WHAT IS KNOWN ALREADY: There is limited understanding of the factors that impact upon how single mothers represent the donor, and whether or not they are determined by specific donor programmes (anonymous or identity-release). STUDY DESIGN, SIZE, DURATION: Qualitative interviews were conducted with 46 women who had treatment at a UK licensed fertility clinic during the years 2003-2009. Twenty mothers (43%) had used an anonymous donor, and 26 (57%) had used an identity-release donor. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among the 46 mothers interviewed, all had at least one child conceived via donor insemination who was between the ages of 4 and 9 years. Mothers were heterosexual and were currently without a live-in and/or long-term partner. Interview data were analysed qualitatively according to the principles of thematic analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Findings indicated marked diversity in single mothers' representations of the donor. Most (n = 27) mothers talked about the donor as symbolically significant to family life and were likely to describe the donor as (i) a gift-giver, (ii) a gene-giver and (iii) a potential partner. Others (n = 16) talked about the donor as (i) unknown, (ii) part of a process and (iii) out of sight and out of mind. There were mothers with anonymous and identity-release donors in each group. Several mothers explained that their feelings about the donor had changed over time. LIMITATIONS, REASONS FOR CAUTION: All mothers conceived at a licensed fertility clinic in the UK. Findings are limited to individuals willing and able to take part in research on donor conception. WIDER IMPLICATIONS OF THE FINDINGS: The study offers greater insight into the factors influencing the donor narratives produced in single-mother families. It has implications for the counselling and treatment of single women seeking fertility treatment with donor gametes in both anonymous and identity-release programmes. Given that the number of clinics offering identity-release programmes worldwide seems to be increasing, the finding that single women may have varying preferences with regard to donor type, and varying interest levels with regard to donor information, is important. It is recommended that clinicians and other fertility clinic staff guard against making assumptions about such preferences and any thoughts and feelings about the donor or donor information on the basis of marital status. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Wellcome Trust [097857/Z/11/Z]. The authors have no conflicts of interest to declare.

In vitro selection of miltefosine resistance in promastigotes of Leishmania donovani from Nepal: genomic and metabolomic characterization.

In this study, we followed the genomic, lipidomic and metabolomic changes associated with the selection of miltefosine (MIL) resistance in two clinically derived Leishmania donovani strains with different inherent resistance to antimonial drugs (antimony sensitive strain Sb-S; and antimony resistant Sb-R). MIL-R was easily induced in both strains using the promastigote-stage, but a significant increase in MIL-R in the intracellular amastigote compared to the corresponding wild-type did not occur until promastigotes had adapted to 12.2 µM MIL. A variety of common and strain-specific genetic changes were discovered in MIL-adapted parasites, including deletions at the LdMT transporter gene, single-base mutations and changes in somy. The most obvious lipid changes in MIL-R promastigotes occurred to phosphatidylcholines and lysophosphatidylcholines and results indicate that the Kennedy pathway is involved in MIL resistance. The inherent Sb resistance of the parasite had an impact on the changes that occurred in MIL-R parasites, with more genetic changes occurring in Sb-R compared with Sb-S parasites. Initial interpretation of the changes identified in this study does not support synergies with Sb-R in the mechanisms of MIL resistance, though this requires an enhanced understanding of the parasite's biochemical pathways and how they are genetically regulated to be verified fully.

Examining the profile of high-potency cannabis and its association with severity of cannabis dependence.

BACKGROUND: Cannabis use is decreasing in England and Wales, while demand for cannabis treatment in addiction services continues to rise. This could be partly due to an increased availability of high-potency cannabis. METHOD: Adults residing in the UK were questioned about their drug use, including three types of cannabis (high potency: skunk; low potency: other grass, resin). Cannabis types were profiled and examined for possible associations between frequency of use and (i) cannabis dependence, (ii) cannabis-related concerns. RESULTS: Frequent use of high-potency cannabis predicted a greater severity of dependence [days of skunk use per month: b = 0.254, 95% confidence interval (CI) 0.161-0.357, p < 0.001] and this effect became stronger as age decreased (b = -0.006, 95% CI -0.010 to -0.002, p = 0.004). By contrast, use of low-potency cannabis was not associated with dependence (days of other grass use per month: b = 0.020, 95% CI -0.029 to 0.070, p = 0.436; days of resin use per month: b = 0.025, 95% CI -0.019 to 0.067, p = 0.245). Frequency of cannabis use (all types) did not predict severity of cannabis-related concerns. High-potency cannabis was clearly distinct from low-potency varieties by its marked effects on memory and paranoia. It also produced the best high, was preferred, and most available. CONCLUSIONS: High-potency cannabis use is associated with an increased severity of dependence, especially in young people. Its profile is strongly defined by negative effects (memory, paranoia), but also positive characteristics (best high, preferred type), which may be important when considering clinical or public health interventions focusing on cannabis potency.

'Friendly allies in raising a child': a survey of men and women seeking elective co-parenting arrangements via an online connection website.

STUDY QUESTION: What are the characteristics, motivations and expectations of men and women who search for a co-parent online? SUMMARY ANSWER: Male and female prospective co-parents differed in terms of their motivations, choice of co-parent and expectations of co-parenting, while differences according to sexual orientation were less marked. WHAT IS KNOWN ALREADY: Very few studies have addressed the experiences of elective co-parents, i.e. men and women who are not in a relationship with each other creating and raising a child together. No study has examined the motivations and experiences of those who seek co-parents online. STUDY DESIGN, SIZE AND DURATION: An online survey was completed by 102 participants (61 men, 41 women) who were members of Pride Angel, an online connection website that facilitates contact between people looking for someone with whom to have a child. The survey was live for 7 weeks. PARTICIPANTS/MATERIALS, SETTING, METHODS: Details of the survey were emailed to all members of Pride Angel. The survey obtained data on participants' demographic characteristics, motivations, choice of co-parent and expectations of co-parenting. Data were analysed to examine differences by gender and by sexual orientation within each gender. MAIN RESULTS AND THE ROLE OF CHANCE: Approximately one-third of men and one half of women seeking co-parenting arrangements were heterosexual. The majority (69, 68%) of participants were single, although significantly more gay and bisexual men (15, 36%) and lesbian and bisexual women (11, 55%) had a partner compared with heterosexual men (4, 20%) and heterosexual women (2, 12%), respectively. Overall, the most important motivation for seeking co-parenting arrangements was in order for both biological parents to be involved in the child's upbringing. Co-parents were looking for someone with a good medical history. Most female co-parents expected the child to live with them, whereas male co-parents either wished the child to reside with the mother or to live equally in both households. A higher proportion of gay and bisexual men than heterosexual men wanted daily contact with the child. LIMITATIONS, REASONS FOR CAUTION: Although this study presents data from the largest sample of elective co-parents to date, the main limitations were the low response rate and that only members of one website were approached. The findings may not be representative of all potential elective co-parents. WIDER IMPLICATIONS OF THE FINDINGS: This study provides important insights into the new phenomenon of elective co-parenting. With the increasing use of assisted reproductive technologies and the diversification of family forms, a growing number of people are seeking co-parenting arrangements to have children. While up until now, elective co-parenting has been principally associated with the gay and lesbian community, this study shows that, with the rise of co-parenting websites, increasing numbers of heterosexual men and women are seeking these types of parenting arrangements. This study generates the first findings on the expectations and motivations of those who seek co-parents online and examines whether these differ according to gender and sexual orientation. Future studies are needed to assess the impact of this new form of parenting on all involved, particularly the children. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Wellcome Trust (097857/Z/11/Z). Erika Tranfield is the co-founder of the website Pride Angel, the remaining authors have no conflicts of interest to declare.

Attentional bias and treatment adherence in substitute-prescribed opiate users.

BACKGROUND: Attentional bias (AB) is implicated in the development and maintenance of substance dependence and in treatment outcome. We assessed the effects of attentional bias modification (ABM), and the relationship between AB and treatment adherence in opiate dependent patients. METHOD: An independent groups design was used to compare 23 opiate dependent patients with 21 healthy controls. Participants completed an AB task before either a control or an ABM task designed to train attention away from substance-related stimuli. Pre- and post-ABM AB and craving were assessed to determine any changes. Relationships between treatment adherence ('using on top' of prescribed opiates or not) and AB, craving and psychopathology were also examined. RESULTS: There was no baseline difference in AB between patients and controls, and no significant effect of ABM on AB or substance craving. However, treatment adherent patients who did not use illicit opiates on top of their prescribed opiates had statistically significantly greater AB away from substance-related stimuli than both participants using on top and controls, and reported significantly lower levels of craving than non-treatment adherent patients. CONCLUSION: Whilst we did not find any significant effects of ABM on AB or craving, patients who were treatment adherent differed from both those who were not and from controls in their attentional functioning and substance craving. These findings are the first to suggest that AB may be a within-treatment factor predictive of adherence to pharmacological treatment and potentially of recovery in opiate users.