Search

Background: In 2004, the term acute kidney injury (AKI) was introduced with the intention of broadening our understanding of rapid declines in renal function and to replace the historical terms of acute renal failure and acute tubular necrosis (ATN). Despite this evolution in terminology, the mechanisms of AKI have stayed largely elusive with the pathophysiological concepts of ATN remaining the mainstay in our understanding of AKI. Summary: The proximal tubule (PT), having the highest mitochondrial content in the kidney and relying heavily on oxidative phosphorylation to generate ATP, is vulnerable to ischaemic insults and mitochondrial dysfunction. Histologically, pathological changes in the PT are more consistent than changes to the glomeruli or the loop of Henle in AKI. Physiologically, activation of tubuloglomerular feedback due to PT dysfunction leads to an increase in preglomerular afferent arteriole resistance and a reduction in glomerular filtration. Pharmacologically, frusemide – a drug commonly used in the setting of oliguric AKI – is actively secreted by the PT and its diuretic effect is compromised by its failure to be secreted into the urine and thus be delivered to its site of action at the loop of Henle in AKI. Increases in the urinary, but not plasma biomarkers, of PT injury within 1 h of shock suggest that the PT as the initiation pathogenic target of AKI. Key Message: Therapeutic agents targeting specifically the PT epithelial cells, in particular its mitochondria – including amino acid ergothioneine and superoxide scavenger MitoTEMPO – show great promises in ameliorating AKI.

The past 2 Myr have seen both unprecedented environmental instability and the evolution of the human capacity for complex culture. This, along with the observation that cultural evolution occurs faster than genetic evolution, has led to the suggestion that culture is an adaptation to an unstable environment. We test this hypothesis by examining the ability of human social learning to respond to environmental changes. We do this by inserting human participants ( n = 4800) into evolutionary simulations with a changing environment while varying the social information available to individuals across five conditions. We find that human social learning shows some signs of adaptation to environmental instability, including critical social learning, the adoption of up-and-coming traits and, unexpectedly, contrariness. However, these are insufficient to avoid significant fitness declines when the environment changes, and many individuals are highly conformist, which exacerbates the fitness effects of environmental change. We conclude that human social learning reflects a compromise between the competing needs for flexibility to accommodate environmental change and fidelity to accurately transmit valuable cultural information.

RationaleRumination is a repetitive, negative, self-focused thinking style associated with various forms of psychopathology. Recent studies suggest that rumination increases craving for alcohol and predicts harmful drinking and alcohol-related problems. However, the acute effects of alcohol on rumination have not been previously studied. It is proposed that alcohol may reduce ruminative thinking through decreasing negative mood.ObjectivesIn the present study, we aimed to test the previously unexplored effects of acute alcohol consumption on rumination in a hazardous drinking population.MethodsWe conducted a randomised placebo-controlled laboratory study to examine the effect of low (0.4 g kg−1) and high doses (0.8 g kg−1) of alcohol on state rumination compared to placebo. Participants completed a rumination induction task prior to receiving drinks. We then measured state rumination and mood at repeated time points; 30 min, 60 min and 90 min post-drinks consumption.ResultsWe found a significant decrease in state rumination in the low-dose alcohol group compared to placebo at 30 min post-alcohol consumption, but no difference was observed between the high-dose alcohol and placebo groups. Mediation analysis provided evidence for an indirect effect of alcohol on state rumination through concurrent changes in negative mood.ConclusionsThese findings suggest that acute alcohol consumption can regulate negative mood and concurrently rumination, providing preliminary evidence for the role of rumination in alcohol use disorders. Rumination may be a treatment target in alcohol use disorders.

Background The percentage of older patients undergoing surgery for early-stage breast cancer has decreased over the past decade. This study aimed to develop a prediction model for postoperative complications to better inform patients about the benefits and risks of surgery, and to investigate the association between complications and functional status and quality of life (QoL). Methods Women aged at least 70 years who underwent surgery for Tis-3 N0 breast cancer were included between 2013 and 2018. The primary outcome was any postoperative complication within 30 days after surgery. Secondary outcomes included functional status and QoL during the first year after surgery, as assessed by the Groningen Activity Restriction Scale and the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23 questionnaires. A prediction model was developed using multivariable logistic regression and validated externally using data from the British Bridging the Age Gap Study. Linear mixed models were used to assess QoL and functional status over time. Results The development and validation cohorts included 547 and 2727 women respectively. The prediction model consisted of five predictors (age, polypharmacy, BMI, and type of breast and axillary surgery) and performed well in internal (area under curve (AUC) 0.76, 95 per cent c.i. 0.72 to 0.80) and external (AUC 0.70, 0.68 to 0.72) validations. Functional status and QoL were not affected by postoperative complication after adjustment for confounders. Conclusion This validated prediction model can be used to counsel older patients with breast cancer about the postoperative phase. Postoperative complications did not affect functional status nor QoL within the first year after surgery even after adjustment for predefined confounders. Lay summary Surgery remains the standard of care for the majority of older patients with breast cancer. The percentage of older patients with breast cancer receiving surgery is decreasing. The reason for this decline is unknown, but it might be due to fear of complications. To better inform patients about the benefits and risks of surgery, the aim of this study was to develop a prediction model for complications after surgery. Another important aspect, especially for older adults with breast cancer, is quality of life, functional capacity, and ability to carry out daily tasks (functional status) after therapy. This study showed that quality of life and functional status did not decline after breast surgery, irrespective of the occurrence of postoperative complications.Some 41.0 per cent of older patients with breast cancer developed a postoperative complication within 30 days after surgery. The authors designed a prediction tool that can predict complication risk, with a good internal and external validity. Postoperative complications did not affect functional status or quality of life in the first year after surgery after adjustment for confounders.

X.D. was funded by a grant from the National Institute for Health Research (NIHR) Health Protection Research Unit in Genomics and Enabling Data (no. NIHR200892). M.A.H. was supported by grants from the Medical Research Council (nos. G1001787/1, MR/N002660/1 and MR/P007201/1) and the Economic and Social Research Council (no. ES/S000186/1). E.M.H. was supported by a UK Research and Innovation (UKRI) Fellowship (no. MR/S00291X/1). The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics1. Here we show that particular lineages of methicillin-resistant Staphylococcus aureus—a notorious human pathogen—appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two β-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development. Publisher PDF

BackgroundAcute cannabis administration can produce transient psychotic-like effects in healthy individuals. However, the mechanisms through which this occurs and which factors predict vulnerability remain unclear. We investigate whether cannabis inhalation leads to psychotic-like symptoms and speech illusion; and whether cannabidiol (CBD) blunts such effects (study 1) and adolescence heightens such effects (study 2).MethodsTwo double-blind placebo-controlled studies, assessing speech illusion in a white noise task, and psychotic-like symptoms on the Psychotomimetic States Inventory (PSI). Study 1 compared effects of Cann-CBD (cannabis containing Δ-9-tetrahydrocannabinol (THC) and negligible levels of CBD) with Cann+CBD (cannabis containing THC and CBD) in 17 adults. Study 2 compared effects of Cann-CBD in 20 adolescents and 20 adults. All participants were healthy individuals who currently used cannabis.ResultsIn study 1, relative to placebo, both Cann-CBD and Cann+CBD increased PSI scores but not speech illusion. No differences between Cann-CBD and Cann+CBD emerged. In study 2, relative to placebo, Cann-CBD increased PSI scores and incidence of speech illusion, with the odds of experiencing speech illusion 3.1 (95% CIs 1.3–7.2) times higher after Cann-CBD. No age group differences were found for speech illusion, but adults showed heightened effects on the PSI.ConclusionsInhalation of cannabis reliably increases psychotic-like symptoms in healthy cannabis users and may increase the incidence of speech illusion. CBD did not influence psychotic-like effects of cannabis. Adolescents may be less vulnerable to acute psychotic-like effects of cannabis than adults.

To evaluate regional axonal-related parameters as a function of disease stage in primary open angle glaucoma (POAG) and visual field (VF) sensitivity. Spectral domain optical coherence tomography was used to acquire 20° scans of POAG (n = 117) or healthy control (n = 52) human optic nerve heads (ONHs). Region specific and mean nerve fibre layer (NFL) thicknesses, border NFL and peripapillary NFL, minimum rim width (MRW)/ area (MRA) and prelamina thickness; and volume were compared across POAG disease stages and with visual field sensitivity. Differences identified between early glaucoma (EG), preperimetric glaucoma (PG) and control (C) ONHs included thinner PG prelamina regions than in controls (p p p = 0.049) compared to control eyes; and EG mean, and inferior and ST, border NFL was thinner than in PG (p p p = 0.023). MRW differences included: PG SN and inferior less than in controls (p p p = 0.127) and prelamina volume (p

Background: 3,4-Methylenedioxymethamphetamine (MDMA) is widely known for its positive acute effects on social behaviour, such as increasing empathy, whilst also attenuating the negative impact of social exclusion. However there is a scarcity of research that investigates the long-term impact of recreational MDMA use on these fundamental social processes. Method: Sixty-seven individuals were split into three groups based on their drug-use history: poly-drug MDMA users ( n = 25), poly-drug users who do not use MDMA ( n = 19), alcohol-only users ( n = 23), and were tested in an independent groups design. Participants completed both a self-report measure of emotional and cognitive empathy, along with the Multifaceted Empathy Task – a computerised assessment of empathy – and the Cyberball Game – a social exclusion paradigm. Results: MDMA users had significantly greater subjective emotional empathy, and greater cognitive empathy on the computer task compared with the poly-drug users who do not use MDMA. There were no significant differences in subjective responses to social exclusion between the groups. Indices of MDMA use did not correlate with empathy. Conclusions: Long-term MDMA users in this sample exhibited normal psychosocial functioning in regard to empathy and social pain and had higher subjective emotional empathy. This conflicts with previous suggestions that moderate, long-term MDMA use may cause heightened social distress, and is further evidence of the safety of the drug, which is relevant to considerations of its therapeutic use.

OBJECTIVES: To better understand the role of nutrition in older adults (aged 50 years or older) with bipolar disorders (OABD), we conducted a systematic review of the literature and appraise existing evidence. METHODS: Following PRISMA guidelines, we searched databases including Medline/PubMed, PsychINFO, EMBASE, CINAHL, Scopus, Web of Science, Cochrane Register, FDA website, and clinical trial registries through 2019 for eligible reports. The search string combined MeSH terms for bipolar disorder, nutrition and older adults. This was supplemented by snowball searching of references in relevant studies and authors were contacted to request their work where necessary. All included studies were rated with the National Institutes of Health Study Quality Assessment Tools based on study designs. RESULTS: Of 2280 papers screened, ten studies including eight observational and two interventional studies. The topic foci of the papers examined several nutrients, (including vitamin B12, vitamin D, coenzyme Q10, homocysteine, and folate), nutritional deficiencies and biochemical correlates. The prevalence rates of deficiencies varied with specific nutrients (3.7% to 71.6% for Vitamin B12 and 34.6% for Vitamin D), and between inpatient versus outpatient populations. While nutritional interventions appeared to be associated with improvement in both affective and cognitive outcomes, the sample sizes of OABD varied and were generally small. CONCLUSION: While there is evidence for the benefits of nutritional interventions on affective, cognitive and overall outcome in OABD, the quality of the evidence is limited. Our findings underscore the need for high quality studies to inform evidence-based guidelines for nutritional assessment and supplemention in OABD.

Experiences of childhood trauma (abuse and neglect) are disproportionately higher in those with opioid use disorder (OUD). Childhood trauma may affect the reinforcing and rewarding properties of opioid drugs and responses to pain, potentially via developmental changes to the endogenous opioid system. This has been supported by preclinical research, yet this has not been investigated in non-addicted humans. Physically healthy participants with either a history of severe childhood trauma or no previous history of childhood trauma attended two sessions where they received either an intramuscular active dose of morphine (0.15 mg/kg) or a very low dose control (0.01 mg/kg) in a randomised, double-blind crossover design. Sessions were held 1 week apart. Participants' physical pain threshold and tolerance were measured pre- and post-drug administration using the cold water pressor test, alongside acute subjective and behavioural responses over 2.5 h. The trauma group reported liking the effects of morphine, feeling more euphoric and wanting more of the drug over the session, as well as feeling less nauseous, dizzy, and dislike of the effects of morphine compared to the non-trauma comparison group. Morphine increased pain threshold and tolerance, yet this did not differ between the groups. Childhood trauma may therefore sensitise individuals to the pleasurable and motivational effects of opioids and reduce sensitivity to the negative effects, providing compelling evidence for individual differences in opioid reward sensitivity. This may explain the link between childhood trauma and vulnerability to OUD, with consequent implications on interventions for OUD, the prescribing of opioids, and reducing stigmas surrounding OUD.

Academic journals provide a key quality-control mechanism in science. Yet, information asymmetries and conflicts of interests incentivize scientists to deceive journals about the quality of their research. How can honesty be ensured, despite incentives for deception? Here, we address this question by applying the theory of honest signaling to the publication process. Our models demonstrate that several mechanisms can ensure honest journal submission, including differential benefits, differential costs, and costs to resubmitting rejected papers. Without submission costs, scientists benefit from submitting all papers to high-ranking journals, unless papers can only be submitted a limited number of times. Counterintuitively, our analysis implies that inefficiencies in academic publishing (e.g., arbitrary formatting requirements, long review times) can serve a function by disincentivizing scientists from submitting low-quality work to high-ranking journals. Our models provide simple, powerful tools for understanding how to promote honest paper submission in academic publishing.

Rationale Ketamine may model aspects of schizophrenia arising through NMDA receptor activity deficits. Although acute ketamine can induce effects resembling both positive and negative psychotic symptoms, chronic use may be a closer model of idiopathic psychosis. Objectives We tested the hypotheses that ketamine users had lower brain volumes, as measured using MRI, and greater sub-threshold psychotic symptoms relative to a poly-drug user control group. Methods Ketamine users (n = 17) and poly-drug using controls (n = 19) were included in the study. All underwent volumetric MRI imaging and measurement of sub-threshold psychotic symptoms using the Comprehensive Assessment of At-Risk Mental State (CAARMS). Freesurfer was used to analyse differences in regional brain volume, cortical surface area and thickness between ketamine users and controls. The relationship between CAARMS ratings and brain volume was also investigated in ketamine users. Results Ketamine users were found to have significantly lower grey matter volumes of the nucleus accumbens, caudate nucleus, cerebellum and total cortex (FDR p Conclusions Chronic ketamine use may cause lower grey matter volumes as well as inducing sub-threshold psychotic symptoms, although these likely arise through distinct mechanisms.

Prestige-biased social learning (henceforth “prestige-bias”) occurs when individuals predominantly choose to learn from a prestigious member of their group, i.e. someone who has gained attention, respect and admiration for their success in some domain. Prestige-bias is proposed as an adaptive social-learning strategy as it provides a short-cut to identifying successful group members, without having to assess each person’s success individually. Previous work has documented prestige-bias and verified that it is used adaptively. However, the domain-specificity and generality of prestige-bias has not yet been explicitly addressed experimentally. By domain-specific prestige-bias we mean that individuals choose to learn from a prestigious model only within the domain of expertise in which the model acquired their prestige. By domain-general prestige-bias we mean that individuals choose to learn from prestigious models in general, regardless of the domain in which their prestige was earned. To distinguish between domain specific and domain general prestige we ran an online experiment (n = 397) in which participants could copy each other to score points on a general-knowledge quiz with varying topics (domains). Prestige in our task was an emergent property of participants’ copying behaviour. We found participants overwhelmingly preferred domain-specific (same topic) prestige cues to domain-general (across topic) prestige cues. However, when only domain-general or cross-domain (different topic) cues were available, participants overwhelmingly favoured domain-general cues. Finally, when given the choice between cross-domain prestige cues and randomly generated Player IDs, participants favoured cross-domain prestige cues. These results suggest participants were sensitive to the source of prestige, and that they preferred domain-specific cues even though these cues were based on fewer samples (being calculated from one topic) than the domain-general cues (being calculated from all topics). We suggest that the extent to which people employ a domain-specific or domain-general prestige-bias may depend on their experience and understanding of the relationships between domains.

Background:While the acute effects of cannabis are relatively benign for most users, some individuals experience significant adverse effects. This study aimed to identify whether variation in schizotypal personality traits and frequency of cannabis use influence the acute effects of delta-9-tetrahydrocannabinol (THC).Methods:Individual participant data from four double-blind, randomised, placebo-controlled, acute crossover studies involving 128 cannabis users were combined for a mega-analysis. Using multilevel linear models and moderation analyses, frequency of cannabis use and schizotypal personality traits were investigated as potential moderators of the subjective, cognitive and psychotomimetic effects of acute THC.Results:There was evidence of a moderating effect where increased frequency of cannabis use was associated with reduced intensity of subjective (changes in alertness and feeling stoned) and psychosis-like effects following THC when compared with placebo. Moderating effects of cannabis use frequency on acute memory impairment were weak. Trait schizotypy did not moderate the acute psychosis-like effects of THC compared with placebo.Conclusions:Our results suggest that a pattern of domain-specific tolerance develops to the acute effects of THC. Tolerance to the alertness-reducing effects occurred more readily than tolerance to psychotomimetic effects. Only partial tolerance to feeling stoned was found, and there was weak evidence for tolerance to memory impairment. Trait schizotypy did not moderate THC’s effects on psychotomimetic symptoms.

Conformist transmission is a cognitively simple decision-making process by which observers are disproportionately likely to follow the majority. It has been studied in multiple species because theory suggests it can create stable cultural variation. However, the current theory assumes that while conformist transmission favours the majority, it is otherwise unbiased and does not systematically transform information, even though such biases are widely documented. Here, we relax this assumption, requiring conformist observers to infer the size of the majority from finite observations of their group mates. Because such inference can be subject to bias, it can lead to the biased transformation of transmitted information. We find that when individuals are biased (even weakly) the capacity of conformist transmission to sustain traditions is reduced and, in many cases, removed entirely. This suggests that the emphasis on conformist transmission as a source of stable cultural variation may be misplaced.

Summary Background A substantial and unmet clinical need exists for pharmacological treatment of cannabis use disorders. Cannabidiol could offer a novel treatment, but it is unclear which doses might be efficacious or safe. Therefore, we aimed to identify efficacious doses and eliminate inefficacious doses in a phase 2a trial using an adaptive Bayesian design. Methods We did a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial at the Clinical Psychopharmacology Unit (University College London, London, UK). We used an adaptive Bayesian dose-finding design to identify efficacious or inefficacious doses at a-priori interim and final analysis stages. Participants meeting cannabis use disorder criteria from DSM-5 were randomly assigned (1:1:1:1) in the first stage of the trial to 4-week treatment with three different doses of oral cannabidiol (200 mg, 400 mg, or 800 mg) or with matched placebo during a cessation attempt by use of a double-blinded block randomisation sequence. All participants received a brief psychological intervention of motivational interviewing. For the second stage of the trial, new participants were randomly assigned to placebo or doses deemed efficacious in the interim analysis. The primary objective was to identify the most efficacious dose of cannabidiol for reducing cannabis use. The primary endpoints were lower urinary 11-nor-9-carboxy-δ-9-tetrahydrocannabinol (THC-COOH):creatinine ratio, increased days per week with abstinence from cannabis during treatment, or both, evidenced by posterior probabilities that cannabidiol is better than placebo exceeding 0·9. All analyses were done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov ( NCT02044809 ) and the EU Clinical Trials Register (2013-000361-36). Findings Between May 28, 2014, and Aug 12, 2015 (first stage), 48 participants were randomly assigned to placebo (n=12) and to cannabidiol 200 mg (n=12), 400 mg (n=12), and 800 mg (n=12). At interim analysis, cannabidiol 200 mg was eliminated from the trial as an inefficacious dose. Between May 24, 2016, and Jan 12, 2017 (second stage), randomisation continued and an additional 34 participants were allocated (1:1:1) to cannabidiol 400 mg (n=12), cannabidiol 800 mg (n=11), and placebo (n=11). At final analysis, cannabidiol 400 mg and 800 mg exceeded primary endpoint criteria (0·9) for both primary outcomes. For urinary THC-COOH:creatinine ratio, the probability of being the most efficacious dose compared with placebo given the observed data was 0·9995 for cannabidiol 400 mg and 0·9965 for cannabidiol 800 mg. For days with abstinence from cannabis, the probability of being the most efficacious dose compared with placebo given the observed data was 0·9966 for cannabidiol 400 mg and 0·9247 for cannabidiol 800 mg. Compared with placebo, cannabidiol 400 mg decreased THC-COOH:creatinine ratio by −94·21 ng/mL (95% interval estimate −161·83 to −35·56) and increased abstinence from cannabis by 0·48 days per week (0·15 to 0·82). Compared with placebo, cannabidiol 800 mg decreased THC-COOH:creatinine ratio by −72·02 ng/mL (−135·47 to −19·52) and increased abstinence from cannabis by 0·27 days per week (−0·09 to 0·64). Cannabidiol was well tolerated, with no severe adverse events recorded, and 77 (94%) of 82 participants completed treatment. Interpretation In the first randomised clinical trial of cannabidiol for cannabis use disorder, cannabidiol 400 mg and 800 mg were safe and more efficacious than placebo at reducing cannabis use. Funding Medical Research Council.

Incentives for priority of discovery are hypothesized to harm scientific reliability. Here, we evaluate this hypothesis by developingan evolutionary agent-based model of a competitive scientific process. We find that rewarding priority of discovery causespopulations to culturally evolve towards conducting research with smaller samples. This reduces research reliability and theinformation value of the average study. Increased start-up costs for setting up single studies and increased payoffs for secondaryresults (also known as scoop protection) attenuate the negative effects of competition. Furthermore, large rewards fornegative results promote the evolution of smaller sample sizes. Our results confirm the logical coherence of scoop protectionreforms at several journals. Our results also imply that reforms to increase scientific efficiency, such as rapid journal turnaroundtimes, may produce collateral damage by incentivizing lower-quality research; in contrast, reforms that increase start-up costs,such as pre-registration and registered reports, may generate incentives for higher-quality research.

Tetrahydrocannabinol (THC) and cannabidiol (CBD) are phytocannabinoids being linked with modulation of anxiety and depression. The recognition of emotions in facial expressions (REFE) is impaired in these disorders. Both drugs could modulate anxiety and mood by interfering with REFE. Thus, a systematic review of controlled trials assessing the effects of THC and CBD on REFE was performed. Ten studies describing seven distinct experiments were found (n = 170). THC (7.5-15 mg) did not alter REFE in three experiments, but reduced task performance in other three experiments. CBD did not alter REFE in two experiments, but improved task performance and counteracted the effects of THC in one experiment. THC (≥ 10 mg) and CBD (600 mg) showed opposite effects on brain activation, skin conductance, and anxiety measures with negative/threatening faces. The limited number of studies precludes firm conclusions on the effects of these substances on REFE. Further controlled trials are needed to elucidate the effects of THC and CBD on REFE. The PROSPERO ID for this study is CRD42019135085.

Prestige-biased social learning occurs when individuals preferentially learn from others who are highly respected, admired, copied, or attended to in their group. This form of social learning is argued to reflect novel forms of social hierarchy in human societies, and, by providing an efficient short-cut to acquiring adaptive information, underpin the cumulative cultural evolution that has contributed to our species’ ecological success. Despite these potentially important consequences, little empirical work to date has tested the basic predictions of prestige-biased social learning. Here we provide evidence supporting the key predictions that prestige-biased social learning is used when it constitutes an indirect cue of success, and when success-biased social learning is unavailable. We ran an online experiment (n = 269) in which participants could copy each other in real-time to score points on a general-knowledge quiz. Our implementation of ‘prestige’ was the number of times someone had previously been copied by others. Importantly, prestige was an emergent property of participants’ behaviour during the experiment; no deception or manipulation of prestige was employed at any time. We found that, as predicted, participants used prestige-biased social learning when the prestige cue was an indirect cue of success, and when direct success information was unavailable. This highlights how people flexibly and adaptively employ social learning strategies based on the reliability of the information that such strategies provide.

Research supported in part by an ERC Advanced Grant to K.N.L. (EVOCULTURE, ref: 232823). A.T. was supported by a BBSRC David Phillips Fellowship (BB/H021817/1) and a grant from the ESRC (ES/M006042/1). Women appear to copy other women’s preferences for men’s faces. This ‘mate-choice copying’ is often taken as evidence of psychological adaptations for processing social information related to mate choice, for which facial information is assumed to be particularly salient. No experiment, however, has directly investigated whether women preferentially copy each other’s face preferences more than other preferences. Further, because prior experimental studies used artificial social information, the effect of real social information on attractiveness preferences is unknown. We collected attractiveness ratings of pictures of men’s faces, men’s hands, and abstract art given by heterosexual women, before and after they saw genuine social information gathered in real time from their peers. Ratings of faces were influenced by social information, but no more or less than were images of hands and abstract art. Our results suggest that evidence for domain-specific social learning mechanisms in humans is weaker than previously suggested. Publisher PDF

Introduction An effect of severe acute kidney injury (AKI) is the development of oliguria and subsequent retention of fluid. Recent studies have reported an association between fluid overload and increased mortality in critically ill patients. Achieving fluid balance control through haemofiltration is an important part of dialysis dose delivery in continuous renal replacement therapy (CRRT). Aims (1) Compare the prescribed dose with the delivered dose of dialysis and haemofiltration for CRRT. (2) Identify how interruptions and delays in treatment delivery impact on fluid balance management. Method A retrospective cohort study was undertaken of daily fluid balance and fluid removal for patients who required CRRT. Each observation chart and prescription order for every treatment day was reviewed. Each patient was exposed to the same treatment mode, predilutional continuous veno-venous haemodiafiltration (CVVHDf). A comparison was made of fluid balance control delivered to the patient over 24h against the dose of fluid removal prescribed. Results The observation charts of 46 consecutive patients were reviewed for total of 288 treatment days. Median number of days patients received CRRT was 5 (range 1–31). Median circuit life was 16h (range 0–66). Fluid removal targets did not occur in 75 (26%) treatment days. Median daily fluid removal shortfall was 300mL (range 25–3800mL). Mean number of daily treatment interruptions 1.25, SD±0.49. The most frequent cause of treatment downtime was circuit clotting (45%). Mean length of treatment down time was 3.71, SD±4.36h excluding delays attributed to assessment of renal function. Conclusion In over a quarter of treatment days prescribed fluid removal was not achieved. Frequency of interruptions and delays in resumption of treatment compromised fluid balance control. Daily targets for fluid removal which are not achieved contribute to fluid overload and may compromise the outcome of patients who require CRRT.

We present a review and analysis of the ethical considerations in off-label ketamine use for severe, treatment-resistant depression. The analysis of ethical considerations is contextualised in an overview of the evidence for ketamine use in depression, and a review of the drug's safety profile. We find that, based on current evidence, ketamine use for severe, treatment-resistant depression does not violate ethical principles; however, clinicians and professional bodies must take steps to ensure that guidelines for good practice are enacted, that all experimental and trial data are made available through national registries, and that the risk potential of ketamine treatment continues to be monitored and modelled. We conclude with a set of key recommendations for oversight bodies that would support safe, effective, and ethical use of ketamine in depression.

Furosemide, a loop diuretic, is used to increase urine output in patients with acute kidney injury (AKI). It remains uncertain whether the benefits of furosemide in AKI outweigh its potential harms. We investigated if furosemide influenced oxidative stress in 30 critically ill patients with AKI by measuring changes in F2-isoprostanes (F2-IsoPs), markers of in vivo oxidative stress, in plasma and urine following intravenous furosemide. Urine F2-IsoPs were higher in sepsis (p = 0.001) and increased in proportion to urine furosemide (p = 0.001). The furosemide-induced increase in urine F2-IsoPs differed depending on AKI severity (p

Esketamine was recently licensed by the US Food and Drug Administration (FDA) and European Drug Agency (EDA) for use in treatment resistant depression (TRD), and further research indicates ketamine as a possible treatment in other mental health conditions. While the underlying mechanisms remain unclear, it has been hypothesised that ketamine’s acute psychoactive effects may be associated with psychiatric treatment efficacy. We systematically reviewed the evidence for this association. The databases Medline, Embase and PsychInfo were searched up to June 2019. Studies were included if they enrolled adults with a psychiatric diagnosis, assessed acute psychoactive effects using a quantitative measure, and reported on the relationship between acute effects and treatment outcome. We included 21 studies, involving 891 patients. Seventeen studies assessed patients with depression (TRD [k = 14]), three assessed substance use disorders, and one assessed social anxiety disorder. Overall, 41 associations were assessed, of which 26 % were significant. The studies reviewed displayed great variability in terms of methodology and quality of reporting. The most commonly assessed effect was dissociation, measured by the CADSS. Our results suggest that the CADSS total is not consistently associated with antidepressant outcomes. Apart from this, the current literature is too limited to draw definite conclusions on the presence of an association between acute psychoactive effects and mental health outcomes. The field would benefit from consistently employing a priori hypotheses, more transparent reporting and sufficiently powered statistical analyses. Furthermore, the use of a broader range of assessments tools of acute psychoactive effects during ketamine administration would be beneficial.

Objectives: High-level β-lactam resistance in methicillin-resistant Staphylococcus aureus is mediated in the majority of strains by a mecA or mecC gene. In this study, we identified ten mec gene negative MRSA human isolates from Austria and eleven bovine isolates from the UK showing high levels of β-lactam resistance and sought to understand the molecular basis of the resistance observed. Methods: Different antimicrobial resistance testing methods (disk diffusion, Etest and Vitek®2) were used to establish the β-lactam resistance profiles for the isolates and the isolates were further investigated by whole-genome sequencing. Results: A number of mutations (including novel ones) in penicillin-binding proteins, AcrB, YjbH and pbp4-promoter were identified in the resistant isolates but not in closely related susceptible isolates. Importantly, a truncation in the c-di-AMP phosphodiesterase enzyme, GdpP, was identified in seven of the ten Austrian isolates and ten of the eleven UK isolates. Complementation of four representative isolates with an intact copy of gdpP gene restored susceptibility to penicillins and abolished the growth defects caused by the truncation. Conclusion: This study reports naturally occurring inactivation of GdpP protein in S. aureus of both human and animal origins, and demonstrated clinical relevance to a previously reported association between this truncation and increased β-lactam resistance and impaired bacterial growth in laboratory generated mutants. It also highlights possible limitations of genomic determination of antibiotic susceptibility based on single gene presence or absence when choosing the appropriate antimicrobial treatment for patients.

© 2019 Morgan et al. Cultural evolution is the product of the psychological mechanisms that underlie individual decision making. One commonly studied learning mechanism is a disproportionate preference for majority opinions, known as conformist transmission. While most theoretical and experimental work approaches the majority in terms of the number of individuals that perform a behaviour or hold a belief, some recent experimental studies approach the majority in terms of the number of instances a behaviour is performed. Here, we use a mathematical model to show that disagreement between these two notions of the majority can arise when behavioural variants are performed at different rates, with different salience or in different contexts (variant overrepresentation) and when a subset of the population act as demonstrators to the whole population (model biases). We also show that because conformist transmission changes the distribution of behaviours in a population, how observers approach the majority can cause populations to diverge, and that this can happen even when the two approaches to the majority agree with regards to which behaviour is in the majority. We discuss these results in light of existing findings, ranging from political extremism on twitter to studies of animal foraging behaviour. We conclude that the factors we considered (variant overrepresentation and model biases) are plausibly widespread. As such, it is important to understand how individuals approach the majority in order to understand the effects of majority influence in cultural evolution. Research Foundation Flanders (FWO)

In an increasing number of states and countries, cannabis now stands poised to join alcohol and tobacco as a legal drug. Quantifying the relative adverse and beneficial effects of cannabis and its constituent cannabinoids should therefore be prioritized. Whereas newspaper headlines have focused on links between cannabis and psychosis, less attention has been paid to the much more common problem of cannabis addiction. Certain cognitive changes have also been attributed to cannabis use, although their causality and longevity are fiercely debated. Identifying why some individuals are more vulnerable than others to the adverse effects of cannabis is now of paramount importance to public health. Here, we review the current state of knowledge about such vulnerability factors, the variations in types of cannabis, and the relationship between these and cognition and addiction.

Humans possess an unusual combination of traits, including our cognition, life history, demographics and geographical distribution. Many theories propose that these traits have coevolved. Such hypotheses have been explored both theoretically and empirically, with experiments examining whether human behaviour meets theoretical expectations. However, theory must make assumptions about the human mind, creating a potentially problematic gap between models and reality. Here, we employ a series of ‘experimental evolutionary simulations' to reduce this gap and to explore the coevolution of learning, memory and childhood. The approach combines aspects of theory and experiment by inserting human participants as agents within an evolutionary simulation. Across experiments, we find that human behaviour supports the coevolution of learning, memory and childhood, but that this is dampened by rapid environmental change. We conclude by discussing both the implications of these findings for theories of human evolution and the utility of experimental evolutionary simulations more generally. This article is part of the theme issue ‘Life history and learning: how childhood, caregiving and old age shape cognition and culture in humans and other animals'.

In a process known as the Baldwin Effect, developmental plasticity, such as learning, has been argued to accelerate the biological evolution of high-fitness traits, including language and complex intelligence. Here we investigate the evolutionary consequences of developmental plasticity by asking which aspects of a plastic trait are the focus of genetic change. The aspects we consider are: (i) dependencies between elements of a trait, (ii) the importance of each element to fitness, and (iii) the difficulty of acquiring each element through plasticity. We also explore (iv) how cultural inheritance changes the relationship between plasticity and genetic change. We find that evolution by natural selection preferentially fixes elements that are depended upon by others, important to fitness, or difficult to acquire through plasticity, but that cultural inheritance can suppress and even reverse genetic change. We replicate some of these effects in experimental evolutionary simulations with human learners. We conclude that what the Baldwin Effect affects depends upon the mechanism of plasticity, which for behavior and cognition includes the psychology of learning.

Little is known about the neural functioning that underpins drug valuation and choice in addiction, including nicotine dependence. Following ad libitum smoking, 19 dependent smokers (smoked≥10/day) and 19 occasional smokers (smoked 0.5-5/week) completed a decision-making task. First, participants stated how much they were willing-to-pay for various amounts of cigarettes and shop vouchers. Second, during functional magnetic resonance imaging, participants decided if they wanted to buy these cigarettes and vouchers for a set amount of money. We examined decision-making behaviour and brain activity when faced with cigarette and voucher decisions, purchasing (vs not purchasing) cigarettes and vouchers, and “value signals” where brain activity correlated with cigarette and voucher value. Dependent smokers had a higher willingness-to-pay for cigarettes and greater activity in the bilateral middle temporal gyrus when faced with cigarette decisions than occasional smokers. Across both groups, the decision to buy cigarettes was associated with activity in the left paracingulate gyrus, right nucleus accumbens, and left amygdala. The decision to buy vouchers was associated with activity in the left superior frontal gyrus, but dependent smokers showed weaker activity in the left posterior cingulate gyrus than occasional smokers. Across both groups, cigarette value signals were observed in the left striatum and ventromedial prefrontal cortex. To summarise, nicotine dependence was associated with greater behavioural valuation of cigarettes and brain activity during cigarette decisions. When purchasing cigarettes and vouchers, reward and decision-related brain regions were activated in both groups. For the first time, we identified value signals for cigarettes in the brain.

Understanding genetic factors that contribute to cannabis use disorder (CUD) is important, but to date, findings have been equivocal. Single-nucleotide polymorphisms (SNPs) in the cannabinoid receptor 1 gene (CNR1; rs1049353 and rs806378) and fatty acid amide hydrolase (FAAH) gene (rs324420) have been implicated in CUD. Their relationship to addiction endophenotypes such as cannabis-related state satiety, the salience of appetitive cues, and craving after acute cannabinoid administration has not been investigated. Forty-eight cannabis users participated in a double-blind, placebo-controlled, four-way crossover experiment where they were administered treatments in a randomized order via vaporization: placebo, Δ 9 -tetrahydrocannabinol (THC) (8 mg), THC + cannabidiol (THC + CBD) (8 + 16 mg), and CBD (16 mg). Cannabis-related state satiety, appetitive cue salience (cannabis and food), and cannabis craving were assessed each day. Participants were genotyped for rs1049353, rs806378, and rs324420. Results indicated that CNR1 rs1049353 GG carriers showed increased state satiety after THC/THC + CBD administration in comparison with placebo and reduced the salience of appetitive cues after THC in comparison with CBD administration; A carriers did not vary on either of these measures indicative of a vulnerability to CUD. CNR1 rs806378 CC carriers showed greater salience to appetitive cues in comparison with T carriers, but there was no evidence for changes in state satiety. FAAH rs324420 A carriers showed greater bias to appetitive cues after THC, in comparison with CC carriers. FAAH CC carriers showed reduced bias after THC in comparison with CBD. No SNPs modulated craving. These findings identify candidate neurocognitive mechanisms through which endocannabinoid system genetics may influence vulnerability to CUD.

Health services in Tasmania, Victoria and now Western Australia are changing to goals-of-care (GOC) advance care planning (ACP) documentation strategies.To compare the clinical impact of two different health department-sanctioned ACP documentation strategies.A non-blinded, pre-post, controlled study over two corresponding 6-month periods in 2016 and 2017 comparing the current discretional not-for-resuscitation (NFR) with a new, inclusive GOC strategy in two medical/oncology wards at a large private hospital. Main outcomes were the uptake of ACP forms per hospitalisation and the timing between hospital admission, ACP form completion and in-patient death. Secondary outcomes included utilisation of the rapid response team (RRT), palliative and critical care services.In total, 650 NFR and 653 GOC patients underwent 1885 admissions (mean Charlson Comorbidity Index = 3.7). GOC patients had a higher uptake of ACP documentation (346 vs 150 ACP forms per 1000 admissions, P0.0001) and a higher proportion of ACP forms completed within the first 48 h of admission (58 vs 39%, P = 0.0002) but a higher incidence of altering the initial ACP level of care (P = 0.003). All other measures, including ACP documentation within 48 h of death (P = 0.50), activation of RRT (P = 0.73) and admission to critical (P = 0.62) or palliative (P = 0.81) care services, remained similar. GOC documentation was often incomplete, with most sub-sections left blank between 74 and 87% of occasions.Despite an increased uptake of the GOC form, overall use remained low, written completion was poor, and most quantitative outcomes remained statistically unchanged. Further research is required before a wider GOC implementation can be supported in Australia's healthcare systems.

The cananga tree alkaloid sampangine (1) has been extensively investigated for its antimicrobial and antitumor potential. Mechanistic studies have linked its biological activities to the reduction of cellular oxygen, the induction of reactive oxygen species (ROS), and alterations in heme biosynthesis. Based on the yeast gene deletion library screening results that indicated mitochondrial gene deletions enhanced the sensitivity to 1, the effects of 1 on cellular respiration were examined. Sampangine increased oxygen consumption rates in both yeast and human tumor cells. Mechanistic investigation indicated that 1 may have a modest uncoupling effect, but predominately acts by increasing oxygen consumption independent of mitochondrial complex IV. Sampangine thus appears to undergo redox cycling that may involve respiratory chain-dependent reduction to a semi-iminoquinone followed by oxidation and consequent superoxide production. Relatively high concentrations of 1 showed significant neurotoxicity in studies conducted with rat cerebellar granule neurons, indicating that sampangine use may be associated with potential neurotoxicity.

With increasing rates of bariatric surgery and the consequential involvement of increasingly complex patients, uncertainty remains regarding the use of intensive care unit (ICU) services after bariatric surgery. Our objective was to define the incidence, indications, and outcomes of patients requiring ICU admission after bariatric surgery and assess whether unplanned ICU admission could be predicted using preoperative factors.All adult bariatric surgery patients between 2007 and 2011 in Western Australia were identified from the Department of Health Data Linkage Unit database and merged with a separate database encompassing all subsequent ICU admissions pertaining to bariatric surgery. The minimal and mean follow-up periods were 12 months and 3.4 yr, respectively.Of the 12 062 patients who underwent bariatric surgery during the study period, 590 patients (4.9%; 650 ICU admissions) were admitted to an ICU after their bariatric surgery. Patients admitted to the ICU were older (48 vs 43 yr, P0.001), more likely to be male (49.7 vs 20.2%, P0.001), and more likely to require revisional bariatric surgery (14.4 vs 7.1%, P0.001). One hundred and seventy-six patients required an emergent unplanned ICU admission, with 51 requiring multiple ICU admissions. Revisional or open surgery, diabetes mellitus, chronic respiratory disease, and obstructive apnoea were the strongest preoperative factors associated with unplanned ICU admission.Intensive care unit admission after bariatric surgery was uncommon (4.9% of all patients), with 30.9% of all referrals being unplanned. A nomogram and smartphone application based on five important preoperative factors may assist anaesthetists to conduct preoperative planning for high-risk bariatric surgical patients.

A multidisciplinary bariatric surgical approach is currently the most effective treatment for obesity. However, little is known about how the physiologic impact of weight reduction surgery superimposed on premorbid obesity-related co-morbidities may adversely influence perioperative renal function.This observational, multicenter study investigated all bariatric surgery patients (n = 590) admitted to any intensive care unit (ICU) in Western Australia between 2007 and 2011. Using Acute Kidney Injury Network (AKIN) criteria, we ascertained the incidence and contributing risk factors for acute kidney injury (AKI).Acute kidney injury (AKI) occurred in 103 patients, accounting for 17.5% of all ICU admissions after bariatric surgery with 76.8% of the AKI episodes limited to AKIN stage 1. In a multivariate analysis, male gender, premorbid hypertension, higher admission APACHE II scores, and blood transfusions were all associated with AKI, while preexisting chronic kidney disease and body mass index (BMI) appeared not to influence renal decline. Both ICU (6.7 versus 2.5 d, P.001) and hospital (18.6 versus 6.8 d, P.001) length of stays were significantly increased after AKI. Six patients required hemodialysis while both ICU mortality (2.9 versus 0%, P = .005) and long-term mortality (18.2 versus 4.7 deaths per 1000 bariatric patient-yr, P = .01) were greater in patients experiencing AKI.AKI is common in bariatric patients requiring critical care support leading to increased healthcare utilization, prolonged hospitalization, and is associated with a higher mortality. BMI, a previously described risk factor, was not predictive of AKI in this cohort.

Objective: To determine the long-term outcomes, health care utilization, and risk factors for complications after bariatric surgery. Background: With the burgeoning problem of obesity and the consequential rise in bariatric surgery, uncertainty remains as to whether this has been matched by a reduction in long-term health care utilization. Methods: A population-based linked-data cohort study, utilizing a comprehensive set of data, including detailed comorbidity and complications, of each individual who had undergone bariatric surgery between 2007 and 2011 in Western Australia. Records were obtained via data linkage through the Western Australian Department of Health Data Linkage Unit. Every patient was followed for a minimum of 12-months after surgery or until death. Results: A total of 12062 patients underwent bariatric surgery during the study period with a mean follow-up period of 41 months. Hospitalization rates after bariatric surgery were substantially reduced for all-cause (361 vs 501 per 1000 patient-years, P = 0.002) and diabetes mellitus-related (7 vs 31 per 1000 patient-years, P < 0.001) diagnoses when compared with hospitalization rates before bariatric surgery. Complications occurred in 2171 (18.0%) patients during the follow-up period. Patient age, sex, open surgical procedures, and Charlson Comorbidity Index were associated with an increased risk of complications, with age the most important and accounting for 77% of the variability in the risk of complications. Long-term all-cause mortality rate after surgery was extremely low (0.54 deaths per 1000 patient-years). Conclusions: When measured against long-term safety outcomes, bariatric surgery has lowmortality andmorbidity associated with a significant reduction in subsequent hospitalizations.

It is uncertain whether bariatric surgery can be safely performed in secondary hospitals without on-site intensive care unit (ICU) support. This study describes the outcomes of elective bariatric surgery patients who required inter-hospital transfers for unplanned ICU management, extrapolating this as a parameter for secondary hospital safety after bariatric surgery. This was a retrospective, statewide, population-based, linked data cohort study capturing all adult bariatric surgery patients for an entire Australian state between 2007 and 2011 (n = 12,062) with minimum 12-month follow-up. In secondary hospitals, 2663 (22.1 %) bariatric patients were operated on, with the majority (n = 2553) undergoing sleeve gastrectomies (SG) or adjustable gastric bands (LAGB). Forty-two patients (including 19 LAGB and 20 SG) required inter-hospital transfer to a tertiary hospital for unplanned ICU care (1.6 %, 95 % confidence interval 1.2–2.1), mainly due to surgical complications. Inter-hospital transfers incurred two deaths, both following sleeve gastrectomies. When compared to patients requiring unplanned ICU admissions after bariatric surgery in tertiary hospitals with an on-site ICU (n = 155), there was no difference in their demographic parameters, comorbid illnesses, or mortality (4.8 vs 3.9 %, p = 0.68). The mortality following bariatric procedures both statewide (0.2 %) and in secondary hospitals (0.2 %) was both uncommon and comparable. Statewide inter-hospital transfers for unplanned ICU care from secondary hospitals were low. Inter-hospital transfer mortality was comparable to a similar bariatric cohort requiring unplanned ICU care after surgery in a tertiary hospital. This suggests that certain bariatric procedures can be safely done in most secondary hospitals where elective ICU admission is deemed unnecessary.

Acute administration of the primary psychoactive constituent of cannabis, Δ-9-tetrahydrocannabinol (THC), impairs human facial affect recognition, implicating the endocannabinoid system in emotional processing. Another main constituent of cannabis, cannabidiol (CBD), has seemingly opposite functional effects on the brain. This study aimed to determine the effects of THC and CBD, both alone and in combination on emotional facial affect recognition. 48 volunteers, selected for high and low frequency of cannabis use and schizotypy, were administered, THC (8mg), CBD (16mg), THC+CBD (8mg+16mg) and placebo, by inhalation, in a 4-way, double-blind, placebo-controlled crossover design. They completed an emotional facial affect recognition task including fearful, angry, happy, sad, surprise and disgust faces varying in intensity from 20% to 100%. A visual analogue scale (VAS) of feeling ‘stoned’ was also completed. In comparison to placebo, CBD improved emotional facial affect recognition at 60% emotional intensity; THC was detrimental to the recognition of ambiguous faces of 40% intensity. The combination of THC+CBD produced no impairment. Relative to placebo, both THC alone and combined THC+CBD equally increased feelings of being ‘stoned’. CBD did not influence feelings of ‘stoned’. No effects of frequency of use or schizotypy were found. In conclusion, CBD improves recognition of emotional facial affect and attenuates the impairment induced by THC. This is the first human study examining the effects of different cannabinoids on emotional processing. It provides preliminary evidence that different pharmacological agents acting upon the endocannabinoid system can both improve and impair recognition of emotional faces.

Background No study has examined ketamine users’ psychiatric morbidity using structured diagnostic instruments. The aim of this study was thus to determine the psychiatric comorbidity of community-based ketamine users using the Structured Clinical Interview for DSM-IV ( Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), Axis I Disorders (SCID). Methods A convenience sample of 200 frequent ketamine users was recruited from community organizations in Hong Kong. Participants were screened with the Severity of Dependence Scale (SDS), Beck Depression Inventory (BDI), Anxiety subscale of the Hospital Anxiety Depression Scale (HADSA), and SCID psychotic symptoms. Those who scored above the threshold (cutoff point of 8/9 on the BDI and 4/5 on HADSA) or displayed evidence of psychotic symptoms were referred for a structured clinical interview conducted by a psychiatrist. Results One hundred and seventy participants scored above the cutoff point on 1 or more of the scales, and 115 participants attended the SCID interview. Fifty-one of these 115 participants received a psychiatric diagnosis of 1 or more comorbidities for the month preceding the interview. Mood disorders accounted for 80.4% of the diagnoses, anxiety disorders for 33.3%, and psychotic disorders for 7.8%. Conclusions Female gender and history of psychiatric/psychological clinic attendance were significantly associated with comorbid psychiatric disorders, whereas ketamine dependence had a borderline association.

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.

Background Increasing mortality for patients admitted to hospitals during the weekend is a contentious but well described phenomenon. However, it remains uncertain whether adverse outcomes, including prolonged hospital length-of-stay (LOS), may also occur after patients undergoing major planned surgery are admitted to an intensive care unit (ICU) out-of-office-hours, either during weeknights (after 18:00) or on weekends. Methods All planned surgical admissions requiring admission to one of 183 ICUs across Australia and New Zealand between 2006 and 2016 were included in this retrospective population-based cohort study. Primary outcomes were hospital LOS and hospital mortality. Results Of the total 504 713 planned postoperative ICU admissions, 33.6% occurred during out-of-office-hours. After adjusting for available risk factors, out-of-office-hours ICU admissions were associated with a significant increase in hospital LOS [+2.6 days, 95% confidence interval (CI) 2.5–2.6], mortality [odd ratio (OR) 1.5, 95%CI 1.4–1.6], and a reduced chance of being directly discharged home (OR 0.8, 95%CI 0.8–0.8). The strongest association for adverse outcomes occurred with weekend ICU admissions (hospital LOS: +3.0 days, 95%CI 3.2–3.6; hospital mortality: OR 1.7, 95%CI 1.6–1.8). Clustering of adverse outcomes by hospitals was not observed in the generalised estimating equation analyses. Conclusions Despite a greater clinical staff availability and higher monitoring levels, planned surgery requiring anticipated out-of-office-hours ICU admission was associated with a prolonged hospital LOS, reduced discharge directly home, and increased mortality compared with in-office-hours admissions. Our findings have potential clinical, economic and health policy implications on how complex planned surgery should be planned and managed.

Background Despite the current shift towards permissive cannabis policies, few studies have investigated the pleasurable effects users seek. Here, we investigate the effects of cannabis on listening to music, a rewarding activity that frequently occurs in the context of recreational cannabis use. We additionally tested how these effects are influenced by cannabidiol, which may offset cannabis-related harms. Methods Across 3 sessions, 16 cannabis users inhaled cannabis with cannabidiol, cannabis without cannabidiol, and placebo. We compared their response to music relative to control excerpts of scrambled sound during functional Magnetic Resonance Imaging within regions identified in a meta-analysis of music-evoked reward and emotion. All results were False Discovery Rate corrected (P

Background The risk of fluid overload and mortality is increased in patients with severe acute kidney injury. Charting of daily fluid balance is a key component of fluid assessment but not without problems affecting accuracy. The introduction of electronic bed scales has made routine patient-weighing easier and focused attention on monitoring fluid-related weight changes. Objectives This paper investigated the frequency of compliance in weighing patients daily using electronic bed scales and evaluated the relationship between calculated fluid balance and body weight changes in patients receiving continuous renal replacement therapy (CRRT). Methods A prospective cohort interventional observation study was conducted in a tertiary ICU between June 2015 and February 2016. All patients who required CRRT, >18 years with an admission >24 hours were enrolled. Each patient was able to be weighed daily using electronic bed scales. At the same time daily fluid balances were calculated using paper-based charting. Trends in compliance of recording body weight changes with daily charting of fluid balances was observed until patient no longer required CRRT. Daily differences were compared using Pearson correlation and Bland-Altman analysis. Results A total of 61 patients were recruited. Four hundred and three days of CRRT was recorded with 286 days (71%) accompanied by a measured body weight. One hundred and eighty-one paired comparisons between body weight change and corresponding fluid balance was obtained from 39 patients (64%). Correlation between changes in body weight with fluid balance was weak (r = 0.34, p Conclusion Change in body weight offers an alternative to charting inputs and outputs in monitoring fluid balance. A physical representation of fluid status is provided rather than a calculated value. Lack of compliance in weighing of patients on two consecutive days was shown to reduce utility as a routine monitoring practice. The relationship between fluid balance and changes in body weight was not strong.

The 'weekend' effect is a controversial theory that links reduced staffing levels, staffing seniority and supportive services at hospitals during 'out-of-office hours' time periods with worsening patient outcomes. It is uncertain whether admitting elective surgery patients to intensive care units (ICU) during 'out-of-office hours' time periods mitigates this affect through higher staffing ratios and seniority.Over a 3-year period in Western Australia's largest private hospital, this retrospective nested-cohort study compared all elective surgical patients admitted to the ICU based on whether their admission occurred 'in-office hours' (Monday-Friday 08.00-18.00 hours) or 'out-of-office hours' (all other times). The main outcomes were surgical complications using the Dindo-Clavien classification and length-of-stay data.Of the total 4363 ICU admissions, 3584 ICU admissions were planned following elective surgery resulting in 2515 (70.2%) in-office hours and 1069 (29.8%) out-of-office hours elective ICU surgical admissions. Out-of-office hours ICU admissions following elective surgery were associated with an increased risk of infection (P = 0.029), blood transfusion (P = 0.020), total parental nutrition (P0.001) and unplanned re-operations (P = 0.027). Out-of-office hours ICU admissions were also associated with an increased hospital length-of-stay, with (1.74 days longer, P0.0001) and without (2.8 days longer, P0.001) adjusting for severity of acute and chronic illnesses and inter-hospital transfers (12.3 versus 9.8%, P = 0.024). Hospital mortality (1.2 versus 0.7%, P = 0.111) was low and similar between both groups.Out-of-office hours ICU admissions following elective surgery is common and associated with serious post-operative complications culminating in significantly longer hospital length-of-stays and greater transfers with important patient and health economic implications.

Published online: 24 July 2017 Alcohol is known to facilitate memory if given after learning information in the laboratory; we aimed to investigate whether this effect can be found when alcohol is consumed in a naturalistic setting. Eighty-eight social drinkers were randomly allocated to either an alcohol self-dosing or a sober condition. The study assessed both retrograde facilitation and alcohol induced memory impairment using two independent tasks. In the retrograde task, participants learnt information in their own homes, and then consumed alcohol ad libitum. Participants then undertook an anterograde memory task of alcohol impairment when intoxicated. Both memory tasks were completed again the following day. Mean amount of alcohol consumed was 82.59 grams over the evening. For the retrograde task, as predicted, both conditions exhibited similar performance on the memory task immediately following learning (before intoxication) yet performance was better when tested the morning after encoding in the alcohol condition only. The anterograde task did not reveal significant differences in memory performance post-drinking. Units of alcohol drunk were positively correlated with the amount of retrograde facilitation the following morning. These findings demonstrate the retrograde facilitation effect in a naturalistic setting, and found it to be related to the self-administered grams of alcohol. The study was funded by an M.R.C. grant to C.J.A.M. (MR/L023032/1), we would like to thank all the participants for their time.

Background: Cannabis is the most widely used illicit drug globally, and users are at increased risk of mental illnesses including psychotic disorders such as schizophrenia. Substance dependence and schizophrenia are both associated with dopaminergic dysfunction. It has been proposed, although never directly tested, that the link between cannabis use and schizophrenia is mediated by altered dopaminergic function. Methods: We compared dopamine synthesis capacity in 19 regular cannabis users who experienced psychotic-like symptoms when they consumed cannabis with 19 nonuser sex- and age-matched control subjects. Dopamine synthesis capacity (indexed as the influx rate constant Kicer) was measured with positron emission tomography and 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine ([18F]-DOPA). Results: Cannabis users had reduced dopamine synthesis capacity in the striatum (effect size: .85; t36 = 2.54, p = .016) and its associative (effect size: .85; t36 = 2.54, p = .015) and limbic subdivisions (effect size: .74; t36 = 2.23, p = .032) compared with control subjects. The group difference in dopamine synthesis capacity in cannabis users compared with control subjects was driven by those users meeting cannabis abuse or dependence criteria. Dopamine synthesis capacity was negatively associated with higher levels of cannabis use (r = −.77, p < .001) and positively associated with age of onset of cannabis use (r = .51, p = .027) but was not associated with cannabis-induced psychotic-like symptoms (r = .32, p = .19). Conclusions: These findings indicate that chronic cannabis use is associated with reduced dopamine synthesis capacity and question the hypothesis that cannabis increases the risk of psychotic disorders by inducing the same dopaminergic alterations seen in schizophrenia.

Dear SirWhile preparing for our ERASMUS + scheme European placement, we were interested to read “12 Tips for Effective International Clinical Placement” (Balandin et al. 2007). Now in our fifth yea...