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Based on the best-selling Stahl's Prescriber's Guide, this essential guide to psychiatric prescribing has been developed by leading psychiatrists and medical students from the University of Cambridge to support all mental health professionals in achieving optimal care for their patients. Written with the authority of evidence and the guidance of clinical wisdom the formulary covers the psychotropic medications used in daily care including dosing recommendations and drug interactions. With its easy-to-use, full-colour template-driven navigation system, the book combines evidence-based data with clinically informed advice, including guidance on prescribing for children and adolescents and people with addictions. Drugs are presented in the same format to facilitate rapid access to information and are broken down into sections designated by a unique colour background thereby clearly distinguishing information presented on therapeutics, side effects, dosing and use, and the art of psychopharmacology. Popular prescribing 'tips and pearls are included throughout.
Cambridge Textbook of Neuroscience for Psychiatrists is a 'one stop shop' for what any psychiatrist needs to know about the brain. Understanding the brain and mind requires a vast array of techniques and conceptual approaches. The Editors have assembled a team of basic neuroscientists, geneticists, psychologists, psychiatrists, neurologists, neurosurgeons and endocrinologists who bring you the cutting edge of translational neuroscience that addresses the material most relevant to current or future psychiatric practice. The book showcases what is known, highlights aspects that are less well understood and defines key outstanding questions. A revolution in our understanding of the brain has, so far, done little to disrupt mainstream psychiatric practice. That is set to change. The chapters align with the UK MRCPsych neuroscience syllabus and link to the USA National Neuroscience Curriculum Initiative (NNCI). Highly illustrated and accessible, this book will appeal to psychiatrists, neuroscientists, psychologists, other healthcare students and professionals.
Partial anomalous venous connection with sinus venosus atrial septal defect is repaired with different approaches including the Warden procedure. Complications include stenosis of the superior caval vein and pulmonary venous baffle; however, cyanosis is rarely seen post-operatively. We report a patient presenting with cyanosis 5 years after a Warden, which was treated with a transcatheter approach.
This paper describes the results from a project to obtain radiocarbon determinations from Early Bronze Age log coffin burials. Log coffins have been recognised as a burial tradition since antiquarian excavations uncovered the first examples. However, comparatively few are associated with radiocarbon determinations and many old determinations are very imprecise. To address this, seven log coffin burials were identified across England, and 11 samples from these were submitted for radiocarbon dating. The dates from the project were reviewed with previously obtained reliable determinations to reconsider the origins and development of the log coffin burial by region. The resulting study indicates that the earliest log coffins were associated with Beaker burials but that regional variations involving different rites soon developed.
In May 1954, the story broke internationally of Marta Olmos, recipient of the first widely known, male-to-female sex reassignment conducted in Mexico. Her doctor, Rafael Sandoval Camacho, claimed that homosexuality could be cured and that, through transitions, queer Mexicans could be made into ‘socially useful’ citizens. While initially celebrated as a scientific triumph placing Mexico among elite nations, and receiving support from individuals close to the Ruiz Cortines administration, opinions soured as critics – physicians, politicians, cartoonists and clerics – condemned Marta for renouncing manhood through a fraudulent cure that threatened the binary sex/gender order underpinning Mexican nationalism. Sex reassignment, understood through foreigners including Christine Jorgensen and associated with ‘anti-social’ queer Mexicans, thus exemplified misplaced priorities during a period in which the state sought to ‘modernise patriarchy’. While self-affirming for Marta and permitted unofficially through state indifference, sex reassignment became seen as anti-Mexican. Thus, Marta's case illuminated how the state reconciled development with policing its patriarchal order.
US policies require robust nursing home (NH) infection prevention and control (IPC) programs to ensure safe care. We assessed IPC resources and practices related to catheter and non–catheter-associated urinary tract infection (CAUTI and UTI) prevention among NHs.
We conducted a mixed-methods study from April 2018 through November 2019. Quantitative surveys assessed NH IPC program resources, practices, and communication during resident transfer. Semistructured qualitative interviews focused on IPC programs, CAUTI and UTI prevention practices, and resident transfer processes. Using a matrix as an analytic tool, findings from the quantitative survey data were combined with the qualitative data in the form of a joint display.
Representatives from 51 NHs completed surveys; interviews were conducted with 13 participants from 7 NHs. Infection preventionists (IPs) had limited experience and/or additional roles, and in 36.7% of NHs, IPs had no specific IPC training. IP turnover was often mentioned during interviews. Most facilities were aware of their CAUTI and UTI rates and reported using prevention practices, such as hydration (85.7%) or nurse-initiated catheter discontinuation (65.3%). Qualitative interviewees confirmed use of these practices and expressed additional concerns about overuse of urine testing and antibiotics. Although transfer sheets were used by 84% to communicate about infections, the information received was described as suboptimal.
NHs identified IP challenges related to turnover, limited education, and serving multiple roles. However, most NHs reported awareness of their CAUTI and UTI rates as well as their use of prevention practices. Importantly, we identified opportunities to enhance communication between NHs and hospitals to improve resident care and safety.
Randomised controlled trials (RCTs) of psilocybin have reported large antidepressant effects in adults with major depressive disorder and treatment-resistant depression (TRD). Given psilocybin's psychedelic effects, all published studies have included psychological support. These effects depend on serotonin 2A (5-HT2A) receptor activation, which can be blocked by 5-HT2A receptor antagonists like ketanserin or risperidone. In an animal model of depression, ketanserin followed by psilocybin had similar symptomatic effects as psilocybin alone.
To conduct a proof-of-concept RCT to (a) establish feasibility and tolerability of combining psilocybin and risperidone in adults with TRD, (b) show that this combination blocks the psychedelic effects of psilocybin and (c) provide pilot data on the antidepressant effect of this combination (compared with psilocybin alone).
In a 4-week, three-arm, ‘double dummy’ trial, 60 adults with TRD will be randomised to psilocybin 25 mg plus risperidone 1 mg, psilocybin 25 mg plus placebo, or placebo plus risperidone 1 mg. All participants will receive 12 h of manualised psychotherapy. Measures of feasibility will include recruitment and retention rates; tolerability and safety will be assessed by rates of drop-out attributed to adverse events and rates of serious adverse events. The 5-Dimensional Altered States of Consciousness Rating Scale will be a secondary outcome measure.
This trial will advance the understanding of psilocybin's mechanism of antidepressant action.
This line of research could increase acceptability and access to psilocybin as a novel treatment for TRD without the need for a psychedelic experience and continuous monitoring.
Patients with unbalanced common atrioventricular canal can be difficult to manage. Surgical planning often depends on pre-operative echocardiographic measurements. We aimed to determine the added utility of cardiac MRI in predicting successful biventricular repair in common atrioventricular canal.
We conducted a retrospective cohort study of children with common atrioventricular canal who underwent MRI prior to repair. Associations between MRI and echocardiographic measures and surgical outcome were tested using logistic regression, and models were compared using area under the receiver operator characteristic curve.
We included 28 patients (median age at MRI: 5.2 months). The optimal MRI model included the novel end-diastolic volume index (using the ratio of left ventricular end-diastolic volume to total end-diastolic volume) and the left ventricle–right ventricle angle in diastole (area under the curve 0.83, p = 0.041). End-diastolic volume index ≤ 0.18 and left ventricle–right ventricle angle in diastole ≤ 72° yield a sensitivity of 83% and specificity of 81% for successful biventricular repair. The optimal multimodality model included the end-diastolic volume index and the echocardiographic atrioventricular valve index with an area under the curve of 0.87 (p = 0.026).
Cardiac MRI can successfully predict successful biventricular repair in patients with unbalanced common atrioventricular canal utilising the end-diastolic volume index alone or in combination with the MRI left ventricle–right ventricle angle in diastole or the echocardiographic atrioventricular valve index. A prospective cardiac MRI study is warranted to better define the multimodality characteristic predictive of successful biventricular surgery.
The Harmonized Cognitive Assessment Protocol (HCAP) describes an assessment battery and a family of population-representative studies measuring neuropsychological performance. We describe the factorial structure of the HCAP battery in the US Health and Retirement Study (HRS).
The HCAP battery was compiled from existing measures by a cross-disciplinary and international panel of researchers. The HCAP battery was used in the 2016 wave of the HRS. We used factor analysis methods to assess and refine a theoretically driven single and multiple domain factor structure for tests included in the HCAP battery among 3,347 participants with evaluable performance data.
For the eight domains of cognitive functioning identified (orientation, memory [immediate, delayed, and recognition], set shifting, attention/speed, language/fluency, and visuospatial), all single factor models fit reasonably well, although four of these domains had either 2 or 3 indicators where fit must be perfect and is not informative. Multidimensional models suggested the eight-domain model was overly complex. A five-domain model (orientation, memory delayed and recognition, executive functioning, language/fluency, visuospatial) was identified as a reasonable model for summarizing performance in this sample (standardized root mean square residual = 0.05, root mean square error of approximation = 0.05, confirmatory fit index = 0.94).
The HCAP battery conforms adequately to a multidimensional structure of neuropsychological performance. The derived measurement models can be used to operationalize notions of neurocognitive impairment, and as a starting point for prioritizing pre-statistical harmonization and evaluating configural invariance in cross-national research.
Experiencing mental health stigma during adolescence can exacerbate mental health conditions, reduce quality of life and inhibit young people’s help-seeking for their mental health needs. For young people, education and contact have most often been viewed as suitable approaches for stigma reduction. However, evidence on the effectiveness of these anti-stigma interventions has not been consistent. This systematic review evaluated the effectiveness of interventions to reduce mental health stigma among youth aged 10–19 years. The review followed Cochrane and PRISMA guidelines. Eight databases were searched: PubMed, PsycINFO, MEDLINE, Web of Science, Scopus, EMBASE, British Education Index and CNKI. Hand searching from included studies was also conducted. Randomised controlled trials and experimental designs that included randomised allocation to interventions and control groups were included in the review. Narrative synthesis was employed to analyse the results. A meta-analysis was conducted to determine the effectiveness of included interventions. Twenty-two studies were included in the review. Eight studies reported positive effects, 11 studies found mixed effects and 3 studies reported no effect on indicators of mental health stigma among youth. Seven of the effective studies were education-based. Eleven studies were suitable for meta-analysis, and the multivariate meta-analytic model indicated a small, significant effect at post-intervention (d = .21, p < .001), but not at follow-up (d = .069, p = .347). Interventions to reduce stigma associated with mental health conditions showed small, short-term effects in young people. Education-based interventions showed relatively more significant effects than other types of interventions.
Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.
In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.
Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.
Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.
Background: What is the number and size of motor units, and axonal excitability profile in the early stages of muscle weakness in ALS compared to controls? Methods: We enrolled ALS patients with APB manual strength testing rated four or four-minus (ALS:4-arm) and four-plus (ALS:4+ arm) and control participants >35 years-old from the University of Toronto, University of Alberta and Universidade Federal de Sao Paulo. Mean±SD, one-way ANOVA and ANCOVA of ALSFRS-R, PUMN Score, MUNIX, MUSIX, and nerve-excitability testing using QTRAC TROND protocol were reported. Results: Twenty-five ALS patients and 63 controls were included. Mean MUNIX was significantly lower (p<0.0001) and MUSIX was significantly higher (p<0.001) in both ALS groups compared to controls. Mean strength-duration time constant in the ALS:4- arm (0.50ms±0.11; p<0.05) and superexcitability in both ALS groups (ALS:4- -29.05%±9.24, ALS:4+ -27.67%±8.03; p<0.05) were relatively increased, supporting axonal hyperexcitability. Conclusions: Significant motor unit loss measured by MUNIX is already present at the earliest detection of muscle weakness in ALS. Increased MUSIX and altered axonal physiology are associated with axonal sprouting and geometry change(1), along with ion channel dysfunction(2). Future trials targeting muscle weakness in ALS should consider the altered neuronal physiology during early disease stages and utilize neurophysiological biomarkers only in normal-to-mildly weak muscles.
Background: The incidence of drug resistant epilepsy (DRE) is around 30% patients with epilepsy. Vagus nerve stimulation (VNS) is offered to patients who are not candidates for epilepsy resective surgery, however the results of lesional cases has not been explored previously Methods: The study was a retrospective cohort study that involved patients with DRE implanted with VNS at the Epilepsy program at Western University, Ontario. We classified our VNS cohort based on brain imaging of lesional (L) and nonlesional (NL) epilepsy. Results: The median age was 31.8 years, 70.69% were females. The VNS-L group average age was 31.8 years and the NL 35.2 years. The most common abnormality was nodular heterotropias 31.34% (n=9). 16 patients underwent palliative procedures before the VNS implantation, 12 in VNS-L and 4 in VNS-NL. The median period of follow-up was 69.97 months. 62% of the VNS-L group had a seizure reduction of 50% or greater, compared to 41.38% in the VNS-NL group. Seizure freedom was 10.34% in VNS-L, compared to 6.99% in VNS-NL. Conclusions: This is the first study reporting the outcome of VNS in lesional cases. Our results suggest that VNS in lesional cases is effective. However, a large multicenteric study is needed.
In Southeast Greenland, summer melt and high winter snowfall rates give rise to firn aquifers: vast stores of meltwater buried beneath the ice-sheet surface. Previous detailed studies of a single Greenland firn aquifer site suggest that the water drains into crevasses, but this is not known at a regional scale. We develop and use a tool in Ghub, an online gateway of shared datasets, tools and supercomputing resources for glaciology, to identify crevasses from elevation data collected by NASA's Airborne Topographic Mapper across 29000 km2 of Southeast Greenland. We find crevasses within 3 km of the previously mapped downglacier boundary of the firn aquifer at 20 of 25 flightline crossings. Our data suggest that crevasses widen until they reach the downglacier boundary of the firn aquifer, implying that crevasses collect firn-aquifer water, but we did not find this trend with statistical significance. The median crevasse width, 27 meters, implies an aspect ratio consistent with the crevasses reaching the bed. Our results support the idea that most water in Southeast Greenland firn aquifers drains through crevasses. Less common fates are discharge at the ice-sheet surface (3 of 25 sites) and refreezing at the aquifer bottom (1 of 25 sites).
It is known that the water entry of a body with a recessed, cupped nose can suppress the splash and air cavity typically observed for solid body entry (Mathai, Govardhan & Arakeri, Appl. Phys. Lett., vol. 106, 2015, 064101). However, the interplay between the captive gas in the cup, the cavity and the splash is quite subtle and has not been thoroughly explored. Here we study the cavity and splash dynamics associated with the vertical water entry of cups and find a variety of regimes over a range of Weber numbers ($We_D$) and dimensionless cup depths. Our parameter space spans a transition between slow-developing cavities with long closure times (low $We_D$) to fast-sealing cavities (high $We_D$). An important dynamic event is the evacuation of trapped gas from within the cup, which drives the ensuing cavity and splash behaviour. Through modelling, we predict the conditions for which the evacuating gas inflates a cavity that opens to the atmosphere versus inflating a submerged cavity that suppresses air entrainment from above the surface. We also compare our cup water entry findings to the impact phenomena observed for flat disks, which entrap gas on the front surface similar to cups. In doing so, we reveal the sensitivity of disk splash and cavity behaviour to impact angle, and show that disks share a common regime with cups, in which a thin splash quickly seals on the body. We deduce the mechanisms by which increasing cup depth delays the cavity seal time in this regime. These findings reveal that cups may in fact promote or suppress cavity growth, depending on the cup depth and impact conditions.
Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis.
Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0–11 years), and late (12–17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use.
The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord.
Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.
While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis.
We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case–control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.
We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case–control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case–control status.
Controls (86.1%) and FEPp (75.63%) were most likely to report ‘because of friends’ as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: ‘to feel better’ as their RFUC (χ2 = 50.97; p < 0.001). RFUC ‘to feel better’ was associated with being a FEPp (OR 1.74; 95% CI 1.03–2.95) while RFUC ‘with friends’ was associated with being a control (OR 0.56; 95% CI 0.37–0.83). The path model indicated an association between RFUC ‘to feel better’ with heavy cannabis use and with FEPp-control status.
Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use ‘to feel better’. People who reported their reason for first using cannabis to ‘feel better’ were more likely to progress to heavy use and develop a psychotic disorder than those reporting ‘because of friends’.
We describe the design, validation, and commissioning of a new correlator termed ‘MWAX’ for the Murchison Widefield Array (MWA) low-frequency radio telescope. MWAX replaces an earlier generation MWA correlator, extending correlation capabilities and providing greater flexibility, scalability, and maintainability. MWAX is designed to exploit current and future Phase II/III upgrades to MWA infrastructure, most notably the simultaneous correlation of all 256 of the MWA’s antenna tiles (and potentially more in future). MWAX is a fully software-programmable correlator based around an ethernet multicast architecture. At its core is a cluster of 24 high-performance GPU-enabled commercial-off-the-shelf compute servers that together process in real-time up to 24 coarse channels of 1.28 MHz bandwidth each. The system is highly flexible and scalable in terms of the number of antenna tiles and number of coarse channels to be correlated, and it offers a wide range of frequency/time resolution combinations to users. We conclude with a roadmap of future enhancements and extensions that we anticipate will be progressively rolled out over time.
OBJECTIVES/GOALS: We have designed an analogue of the Vitamin E tocotrienols called tocoflexol, which improves their pharmacokinetic limitations to make it an effective radiation medical countermeasure. Our goal is to demonstrate that tocoflexol is an effective radiomitigator in vivo when administered after exposure to lethal doses of total body irradiation. METHODS/STUDY POPULATION: Tocoflexol was designed using computational techniques to improve binding to ATTP, the key transporter that reduces the rate of elimination of tocols. In vitro studies compared the antioxidant and cell uptake properties to conventional tocotrienols. Next, we used a mouse model of lethal total body irradiation to evaluate its radioprotection efficacy (treating before radiation). To determine the optimal administration route for radiomitigation (treating after radiation), we will test oral and subcutaneous dosing. Mouse survival will be monitored for 30 days after irradiation. Sample tissues will be taken to evaluate the ability of tocoflexol to protect key organs from acute radiation syndrome. The bioavailability of tocoflexol will be evaluated in a rodent model. RESULTS/ANTICIPATED RESULTS: Known Results: Results show that tocoflexol has potent antioxidant properties and high cell uptake. When tocoflexol was administered 24 hours before exposure to lethal doses of radiation, tocoflexol-treated mice showed 100% survival. Anticipated Results: Because of its improved bioavailability and pharmacokinetic properties, we expect that tocoflexol will show radiomitigation efficacy when administered 24 hours after radiation, improving survival and protecting key organ systems from acute radiation syndrome. DISCUSSION/SIGNIFICANCE: There is an unmet need for safe and effective radiomitigators that can offer multi-organ protection and be rapidly administered in the event of nuclear emergencies. Demonstration of radiomitigation efficacy will position tocoflexol as a prime candidate to be developed into a nuclear medical countermeasure and stockpiled for emergencies.